Biosolutions

Estrogen-Receptor Binding Mode Raloxifene

2012-01-21T11:28:00.000+05:30

Raloxifene is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis in postmenopausal women. It was announced on April 17, 2006, that raloxifene is as effective as tamoxifen in reducing the incidence of breast cancer in certain high risk groups of females, though with a reduced risk of thromboembolic events and cataracts in patients taking raloxifene versus those taking tamoxifen. On September 14, 2007, the U.S. Food and Drug Administration announced approval of raloxifene for reducing the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.

There has been criticism in the mainstream oncology press of the way that information about the drug was released.There has been some confusion in the lay media about the meaning of the trial results. There is no specific clinical evidence for the use of raloxifene in the adjuvant treatment of breast cancer over established drugs such as tamoxifen or anastrozole.

PAX3 gene

2012-01-21T10:37:00.002+05:30

The official name of PAX3 gene is “paired box 3". The PAX3 gene belongs to a family of genes that plays a critical role in the formation of tissues and organs during embryonic development. The PAX gene family is also important for maintaining the normal function of certain cells after birth. To carry out these roles, the PAX genes provide instructions for making proteins that attach to specific areas of DNA. By attaching to critical DNA regions, these proteins help control the activity of particular genes. On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo. The protein made by the PAX3 gene directs the activity of other genes (such as MITF) that signal neural crest cells to form specialized tissues or cell types such as limb muscles, bones in the face and skull (craniofacial bones), some nerve tissue, and pigment-producing cells called melanocytes. Melanocytes produce the pigment melanin, which contributes to hair, eye, and skin color. Melanocytes are also found in certain regions of the brain and inner ear.

Location:

PAX3 Gene is present in human chromosome 2 and its coded from region 222,772,850 to 222,871,943 Complement base pairs with 9 exons, the cytogenetic location 2q35-q37.

PAX3 Protein

Disease

Mutations in PAX3 gene causes Waardenburg syndrome Several PAX3 mutations have been identified in people with Waardenburg syndrome, types I and III. Some of these mutations change one of the chemical building blocks (amino acids) used to make the PAX3 protein. Other mutations lead to an abnormally small version of the PAX3 protein. Researchers believe that all PAX3 mutations have the same effect; they destroy the ability of the PAX3 protein to bind to DNA and regulate the activity of other genes. As a result, melanocytes do not develop in certain areas of the skin, hair, eyes, and inner ear, leading to hearing loss and the patchy loss of pigmentation that are characteristic features of Waardenburg syndrome. Additionally, loss of PAX3 protein function disrupts development of craniofacial bones and certain muscles, producing the limb and facial features that are unique to Waardenburg syndrome, types I and III.

Alterations in the activity of the PAX3 gene are associated with some cases of cancer of muscle tissue (alveolar rhabdomyosarcoma) that occur mainly in adolescents and young adults. Gene activity is altered when the PAX3 gene on chromosome 2 is fused with the FOXO1A gene (also called FKHR) on chromosome 13. This fusion event occurs when segments of chromosomes 2 and 13 are rearranged in certain cells that develop into muscle tissue. The fused PAX3-FOXO1A gene may enhance changes that can lead to cancer, such as uncontrolled cell division and cell growth.

# Arnold K., Bordoli L., Kopp J., and Schwede T. (2006). The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling. Bioinformatics, 22,195-201.
# Schwede T, Kopp J, Guex N, and Peitsch MC (2003) SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Research 31: 3381-3385.

# Guex, N. and Peitsch, M. C. (1997) SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modelling. Electrophoresis 18: 2714-2723.

Implications of Embryonic Stem Cells for Cancer Research

2012-01-20T10:59:00.000+05:30

James Alexander Thomson (born December 20, 1958, at Oak Park, Illinois, USA) is an American developmental biologist. He serves as director of regenerative biology at the Morgridge Institute for Research in Madison, Wisconsin, and is a professor at the University of Wisconsin School of Medicine and Public Health. In 2007, he became an adjunct professor in the Molecular, Cellular, and Developmental Biology (MCDB) Department at the University of California, Santa Barbara.[ He is a member of the National Academy of Sciences. In the May 12, 2008, issue of TIME magazine, he was named one of 100 of the most influential people in the world.

Subscribe in a reader

In this Frontiers in Cancer Research lecture from UCSB he explores current understanding how human embryonic cells can form any cell in the body and the implications for cancer research.

About Research Group
Human and non-human primate embryonic stem cells

Group reported the first derivation of embryonic stem (ES) cells from a non-human primate in 1995, work that led us to the first derivation of human ES cells in 1998. Human ES cells are capable of unlimited undifferentiated proliferation, and yet maintain the ability to form all the cells of the body. Much of our early work focused on developing the basic tools (for example, transfection techniques, homologous recombination, and culture conditions) needed to establish human ES cells as a useful experimental model. My group has also been involved in demonstrating the developmental potential of human ES cells in lineage-specific differentiation (such as blood, trophoblast, neural tissue, and heart). Ultimately, the differentiated derivatives of human ES cells could have important applications in transplantation medicine, and we continue some studies of lineage-specific differentiation in collaboration with UW physician scientists.

The current focus of lab is on understanding the ES cell itself. We wish to understand why this cell can form any cell in the body (pluripotency); how an ES cell chooses between self-renewal and the initial decision to differentiate; what determines which developmental transitions are allowed or not-allowed; and how a differentiated cell with limited developmental potential can be reprogrammed to a pluripotent cell.

Anaphylaxis Mechanism of Action

2012-01-20T10:54:00.001+05:30

Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death".[1] It typically results in a number of symptoms including an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites, foods, and medications.
On a pathophysiologic level, anaphylaxis is due to the release of mediators from certain types of white blood cells triggered either by immunologic or non-immunologic mechanisms. It is diagnosed based on the presenting symptoms and signs. The primary treatment is injection of epinephrine, with other measures being complementary.

Mechanism of Action of Vancomycin

2012-01-20T10:42:00.000+05:30

Vancomycin INN ( /væŋkɵˈmaɪsɨn/) is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed,[citation needed] although the emergence of vancomycin-resistant organisms means that it is increasingly being displaced from this role by linezolid (Zyvox) available PO and IV and daptomycin (Cubicin) IV and quinupristin/dalfopristin (Synercid) IV.

Penicillin Side Effects Animation

2012-01-20T10:35:00.000+05:30

The Estrogen Receptor Hormonal Mechanisms

2012-01-20T10:32:00.000+05:30

Estrogen receptor refers to a group of receptors which are activated by the hormone 17β-estradiol (estrogen). Two types of estrogen receptor exist: ER which is a member of the nuclear hormone family of intracellular receptors and the estrogen G protein coupled receptor GPR30 (GPER), which is a G-protein coupled receptor. This article refers to the nuclear hormone receptor ER.

The main function of the estrogen receptor is as a DNA binding transcription factor which regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding.

Estrogen receptor Molecular and cellular mechanism,Steroid hormones are chemical substances secreted by glands in the abdomen with involved in the regulation of variety of the functions including sodium balace,metabolism and reproductive functions.For example

Nerve Growth Factor (NGF) in Alzheimer's disease

2012-01-18T22:42:00.000+05:30

Nerve growth factor (NGF) is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons (nerve cells). It also functions as a signaling molecule.[1][2] It is perhaps the prototypical growth factor, in that it is one of the first to be described. While "nerve growth factor" refers to a single factor,[3] "nerve growth factors" refers to a family of factors also known as neurotrophins.[4] Other members of the neurotrophin family that are well recognized include Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin 4/5 (NT-4/5).

Function and mechanism of action

NGF is critical for the survival and maintenance of sympathetic and sensory neurons. Without it, these neurons undergo apoptosis.[5] Nerve growth factor causes axonal growth. Studies have shown that it causes axonal branching and a bit of elongation.[6] NGF binds with at least two classes of receptors: the p75 LNGFR (for "low-affinity nerve growth factor receptor") neurotrophin receptor (p75(NTR)) and TrkA, a transmembrane tyrosine kinase. Both are associated with neurodegenerative disorders.

NGF binds to high-affinity tyrosine kinase receptor TrkA. This phosphorylates TrkA, which leads to the activation of PI 3 Kinase, ras, and PLC signaling pathways.

There is evidence that NGF circulates throughout the entire body and is important for maintaining homeostasis.

There is also evidence that shows that the precursor to NGF, pro-NGF, may also play important roles due to its abundance. These include apoptotic and neurotrophic properties.

Nicotine Withdrawal Video

2012-01-18T22:36:00.000+05:30

Nicotine Receptors in the Brain

2012-01-18T22:24:00.000+05:30

Your brain is the key player in nicotine's action. Like a computer, your brain processes, stores and uses information. In a computer, information travels in the form of electricity moving through wires; information transfer is a binary process, with switches being either "on" or "off." In your brain, neurons are the cells that transfer and integrate information. Each neuron has thousands of inputs from other neurons throughout the brain. Each of these signals is included in the calculation of whether or not the neuron will pass the signal it receives on to other neurons in the pathway.

How Hormones Work Animation

2012-01-18T21:57:00.000+05:30

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms produce hormones; plant hormones are also called phytohormones. Hormones in animals are often transported in the blood. Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor protein, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses.

Subscribe in a reader

Endocrine hormone molecules are secreted (released) directly into the bloodstream, while exocrine hormones (or ectohormones) are secreted directly into a duct, and from the duct they either flow into the bloodstream or they flow from cell to cell by diffusion in a process known as paracrine signalling.

Nature of hormonal control

Hormonal regulation of some physiological activities involves a hierarchy of cell types acting on each other either to stimulate or to modulate the release and action of a particular hormone. The secretion of hormones from successive levels of endocrine cells is stimulated by chemical signals originating from cells higher up the hierarchical system. The master coordinator of hormonal activity in mammals is the hypothalamus, which acts on input that it receives from the central nervous system.

Other hormone secretion occurs in response to local conditions, such as the rate of secretion of parathyroid hormone by the parathyroid cells in response to fluctuations of ionized calcium levels in extracellular fluid.

Hormone signaling Hormonal signaling across this hierarchy involves the following: 1. Biosynthesis of a particular hormone in a particular tissue 2. Storage and secretion of the hormone 3. Transport of the hormone to the target cell(s) 4. Recognition of the hormone by an associated cell membrane or intracellular receptor protein. 5. Relay and amplification of the received hormonal signal via a signal transduction process: This then leads to a cellular response. The reaction of the target cells may then be recognized by the original hormone-producing cells, leading to a down-regulation in hormone production. This is an example of a homeostatic negative feedback loop. 6. Degradation of the hormone.

As can be inferred from the hierarchical diagram, hormone biosynthetic cells are typically of a specialized cell type, residing within a particular endocrine gland (e.g., the thyroid gland, the ovaries, or the testes). Hormones may exit their cell of origin via exocytosis or another means of membrane transport. However, the hierarchical model is an oversimplification of the hormonal signaling process. Cellular recipients of a particular hormonal signal may be one of several cell types that reside within a number of different tissues, as is the case for insulin, which triggers a diverse range of systemic physiological effects. Different tissue types may also respond differently to the same hormonal signal. Because of this, hormonal signaling is elaborate and hard to dissect.

Interactions with receptors

Most hormones initiate a cellular response by initially combining with either a specific intracellular or cell membrane associated receptor protein. A cell may have several different receptors that recognize the same hormone and activate different signal transduction pathways, or alternatively different hormones and their receptors may invoke the same biochemical pathway.

For many hormones, including most protein hormones, the receptor is membrane associated and embedded in the plasma membrane at the surface of the cell. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the cytoplasm of the cell, often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g. cyclic AMP). Some protein hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.

For hormones such as steroid or thyroid hormones, their receptors are located intracellularly within the cytoplasm of their target cell. In order to bind their receptors these hormones must cross the cell membrane. The combined hormone-receptor complex then moves across the nuclear membrane into the nucleus of the cell, where it binds to specific DNA sequences, effectively amplifying or suppressing the action of certain genes, and affecting protein synthesis. However, it has been shown that not all steroid receptors are located intracellularly, some are plasma membrane associated.

An important consideration, dictating the level at which cellular signal transduction pathways are activated in response to a hormonal signal is the effective concentration of hormone-receptor complexes that are formed. Hormone-receptor complex concentrations are effectively determined by three factors:

1. The number of hormone molecules available for complex formation 2. The number of receptor molecules available for complex formation and 3. The binding affinity between hormone and receptor.

The number of hormone molecules available for complex formation is usually the key factor in determining the level at which signal transduction pathways are activated. The number of hormone molecules available being determined by the concentration of circulating hormone, which is in turn influenced by the level and rate at which they are secreted by biosynthetic cells. The number of receptors at the cell surface of the receiving cell can also be varied as can the affinity between the hormone and its receptor.

Physiology of hormones

Most cells are capable of producing one or more molecules, which act as signaling molecules to other cells, altering their growth, function, or metabolism. The classical hormones produced by cells in the endocrine glands mentioned so far in this article are cellular products, specialized to serve as regulators at the overall organism level. However they may also exert their effects solely within the tissue in which they are produced and originally released.

The rate of hormone biosynthesis and secretion is often regulated by a homeostatic negative feedback control mechanism. Such a mechanism depends on factors which influence the metabolism and excretion of hormones. Thus, higher hormone concentration alone can not trigger the negative feedback mechanism. Negative feedback must be triggered by overproduction of an "effect" of the hormone.

Hormone secretion can be stimulated and inhibited by:

* Other hormones (stimulating- or releasing-hormones) * Plasma concentrations of ions or nutrients, as well as binding globulins * Neurons and mental activity * Environmental changes, e.g., of light or temperature

One special group of hormones is the tropic hormones that stimulate the hormone production of other endocrine glands. For example, thyroid-stimulating hormone (TSH) causes growth and increased activity of another endocrine gland, the thyroid, which increases output of thyroid hormones.

A recently-identified class of hormones is that of the "hunger hormones" - ghrelin, orexin and PYY 3-36 - and "satiety hormones" - e.g., leptin, obestatin, nesfatin-1.

In order to release active hormones quickly into the circulation, hormone biosynthetic cells may produce and store biologically inactive hormones in the form of pre- or prohormones. These can then be quickly converted into their active hormone form in response to a particular stimulus.

Haplotypes Animation

2012-01-18T19:30:00.000+05:30

Haplotype is a set of single nucleotide polymorphisms (SNPs) on a single chromatid that are statistically associated. It is thought that these associations, and the identification of a few alleles of a haplotype block, can unambiguously identify all other polymorphic sites in its region. Such information is very valuable for investigating the genetics behind common diseases, and is collected by the International HapMap Project.

Subscribe in a reader

An organism's genotype may not uniquely define its haplotype. For example, consider a diploid organism and two bi-allelic loci on the same chromosome such as Single Nucleotide Polymorphisms (SNPs). The first locus has alleles A and T with three possible genotypes AA, AT, and TT, the second locus having G and C, again giving three possible genotypes GG, GC, and CC. For a given individual, there are therefore nine possible configurations for the genotypes at these two loci, as shown in the punnett square , which shows the possible genotypes that an individual may carry and the corresponding haplotypes that these resolve to. For individuals that are homozygous at one or both loci, it is clear what the haplotypes are; it is only when an individual is heterozygous at both loci that the phase is ambiguous.

Within the human genome SNPs occur on an average of 1 in 1000 base pairs .researchers have shown the groups of SNPs occur in predictable patterns within sections of DNA.

these inherent sections of 68 SNPs are called haplotype.Within one section of DNA it is believed that there are only 3 to 5 different haplotypes throughout the entire population.

The only unequivocal method of resolving phase ambiguity is by sequencing. However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals.

Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or haplotype phasing techniques. These methods work by applying the observation that certain haplotypes are common in certain genomic regions. Therefore, given a set of possible haplotype resolutions, these methods choose those that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g., parsimony), whereas others use likelihood functions based on different models and assumptions such as the Hardy-Weinberg principle, the coalescent theory model, or perfect phylogeny. These models are combined with optimization algorithms such as expectation-maximization algorithm (EM) or Markov chain Monte Carlo (MCMC).

Carnitine palmitoyltransferase II

2012-01-18T19:08:00.000+05:30

Definition
Carnitine palmitoyltransferase II, also known as CPT2, is a human gene also known has CPTASE

Chromosome: Chromosome 1

Position:1p32

Size Of Gene: 17767 bp (53434689..53452455)

No Exons 5

Description

Carnitine palmitoyltransferase II precursor (CPT2) is a nuclear protein which is transported to the mitochondrial inner membrane. CPT2 together with carnitine palmitoyltransferase I oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders and carnitine palmitoyltransferase II deficiency.[

Disease:

Carnitine palmitoyltransferase II deficiency is a condition that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food (fasting),three main types of carnitine palmitoyltransferase II deficiency are: a lethal neonatal form; a severe infantile form that affects the liver, heart, and muscles (hepatocardiomuscular form); and a less severe form that affects only the muscles (myopathic form). Infants with the lethal neonatal form of this disorder usually experience respiratory failure, liver failure, seizures, and an irregular heart beat (arrythmia) leading to cardiac arrest. In many cases, the brain and kidneys are also abnormal. Usually, affected infants do not survive their first year.

AIDS and the HIV Life Cycle

2012-01-18T18:31:00.000+05:30

Aids and HIV Life cycle lecture was given by Dr.Bruce Walker ,He is Howard Hughes Medical Institute Investigator,and Director for Center for AIDS Research at Harvard University.The lecture starts from HIV structure , various component of HIV virus,Mechanism of HIV , and how HIV causes AIDS,He also talks about why our immune system is unable to stop HIV virus.The lecture uses various case studies of show HIV variability,he also talk about various challenges for designing drugs for HIV .

Subscribe in a reader
Download Video
This lecture explain about HIV manifestation,

Hiv was first found among few gay persons in califonia,it later spread all aroung USA,
This virus are essentially packages of genetic material and are not able to replicate on their won ,But they carry all the information acquired for replication
if you had chickenpox or infectious mono as child you have that virus still alive in your body now the reason it's not causing diseases that you have an effective immune response that it will help you to keep it in check now
when you first became infected with chickenpox you felt really lousy .The part of that feeling of lousy as your immune system trying to respond and fight the invading pathogen and ultimately even though the virus persists in your body you enter into a phase where your a symptomatic and the virus is not causing any problems again with immune system keeping in check
Early symptoms for Aids Patient had fever, chills, shaking, Headache at times loss of appetite joint and muscle pain and malaise skin rashes,and swollen lymph nodes .
It takes more than 3 weeks produce Hiv Antibody
polymerase chain reaction helps to directly quantitative the amount of virus in the bloodstream
people have a transient drop in Cd4 helper cell counts and then T-helper cell levels decline slowly over time until the ultimate development of AIDS.
HIV it's a typical retrovirus ,meaning that it has in outer envelope. in the center it has two copies of RNA as well as an reverse transcriptase Enzyme, which will ultimately turn that RNA into DNA,
The first step in HIV1 life cycle is viral attachment to the CD4 T-cell surface the next step is viral entry which involves a cascade of molecular interactions between the viral envelope glycoprotein and Two T-cell surface receptors a primary receptor and a co-receptor.
The GP 120 subunit of the envelope protein first binds the CD4 primary receptor this induces a conformational change in GP 120 This allows to binds to the co- receptor binding triggers conformational changes in the GP 41 subunit leading to insertion of its N-terminal fusion peptide into the host cell's membrane

CytoToxic T-Cells

2012-01-18T18:26:00.000+05:30

Cytotoxic T-cells is a sub group of T lymphocytes cells that are capable of inducting the death of infected somatic or tumor cells; they kill virus-affected cells, pathogens, and damaged or dysfunctional cells. Most cytotoxic T cells express T-cell receptors (TcRs) that can recognize a specific antigenic peptide bound to Class I MHC molecules, present on all nucleated cells, and a glycoprotein called CD8, which is attracted to non-variable portions of the Class I MHC molecule. The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound closely together during antigen-specific activation. CD8+ T cells are recognized as TC cells once they become activated and are generally classified as having a pre-defined cytotoxic role within the immune system.

Subscribe in a reader

Cytotoxic T cell activation

When a virus attacks the cell, cell starts produces a viral proteins. The ubiquitin molecule tags these proteins and carries it to proteosome, where it digested into small peptide fragments. A peptidase enzyme breaks these fragments, the fragments further move to endoplasm reticulm and gain entry via TAP molecule. Inside the endoplasm reticulum it binds to developing MHC class 1 molecule (only if it has right conformation with it), MHC class1 molecule is carried to cell surface and embedded. This alerts CTL (cytotoxic tcells), which identifies the foreign virus protein in the MHC class 1 molecule.The T-cell receptor in CTL engages a conformational recognition along with the CD8 molecule, which leads to release Granzymes and perfornin to kill virus-affected cell.

Embryonic stem cells without an egg or embryo

2012-01-18T12:15:00.000+05:30

Researchers at Whitehead Institute for Biomedical Research in Cambridge, Mass., have manipulated mouse fibroblasts and turned them into cells with such developmental elasticity that they appear identical to embryonic stem cells.

Subscribe in a reader

Excerpts from the video

Embryonic stem cells have potential to provide people with donor cells which can be used transplantation medicine, one of the problems of embryonic stem cells are they are derived from the embryo and it will not be compatible with immune system of the donor, so the real goal is to generate customized embryonic stem cells, A way that it thought to be accomplished was by nuclear transfer, for example If u take skin cell from a patient and introduce nucleus from the cells into a egg for whose nucleus is removed. The egg is able to reprogram the somatic cell into an embryonic state, from this people are able to isolate customized embryonic cells and those could be new for customized transplantation therapy, there will be no immune rejection.

The problem with this approach is many, it is very complex and inefficient procedure and it only so far in animals (mice only) and secondly there lot of ethical objection in using human embryo and human egg cells for therapy or research, so goal of field is to understand how the egg accomplishes reprogramming the somatic nucleus into embryonic stage once we know the reprogramming rules we could do without the egg.

What we have done in our laboratory was to use the knowledge coming from investigating and finding of molecular circulatory of embryonic stem cells and comparing it with the somatic cells and taking some key regulators or Key switches and express those into the somatic cells .In long process (few weeks) we found that these skin cells become embryonic cells,. Signatures of the reprogrammed cells these cells were indistingusble with normal embryonic stem cells, Molecular expression pattern of the genes is identical, epigenetic stage of these cells are indistinguisable from embryonic stem cells the most important is these reprogrammed cells can do anything biologically as embryonic stem cells with same developmental potency and we tested this by introducing these cells back to embryos of form prim Eric mice and even can contribute to germline, so that it can generate fibroblast after the reprogramming process being introduced we can generate mice, from all,the test we have done ,it appears that these cells have same potential for forming all lineages of the animal but also for therapy has Embryonic stem cell have.

Action Potential in an unmyelinated axon

2012-01-18T11:51:00.000+05:30

An action potential,depicted as a red band, is propagated in one directional along the axon.During an action potential , the inside of the cell membrane becomes positive with respect to the outside.An action potential generates local current that tends to depolarize the membrane immediately adjacent to the action potential,When depolarization caused by the local currents threshold, a new action potential adjacent to the original one.Action potential propagation occurs in one directional because the recently depolarized area of the membrane is in absolute refractory period and cannot generate an action potential.

What is Southern Blot

2012-01-16T14:05:00.000+05:30

Southern blot is a method routinely used in molecular biology to check for the presence of a DNA sequence in a DNA sample. Southern blotting combines agarose gel electrophoresis for size separation of DNA with methods to transfer the size-separated DNA to a filter membrane for probe hybridization. The method is named after its inventor, the British biologist Edwin Southern.The southern blot is used to verify the presence or absence of a specific nucleotide sequence in the DNA from different sources and to identify the size of the restriction fragment that contains the sequence.

Subscribe in a reader

In this procedure, the DNA is isolated from each source and then digested with a specific restriction enzyme. The DNA restriction fragments are then loaded onto an agrose gel and the fragments separated by electrophoresis according to size, with the smaller fragments migrating faster than larger fragments. The DNA is then transferred from the fragile gel to a nylon filter.

Next the radioactively labeled nucleic acid probe is added. The probe binds to complementary DNA segments. Note that the DNA segment being probed is not present in organism B

To detect the position of the radioactive probe, the nylon membrane is covered with an X-ray film. After development, the positions of the probe become visible.

Prozac: Selective Serotonin Reuptake Inhibitor

2012-01-16T14:02:00.001+05:30

This animation shows how Prozac® alleviates depression. It can also be used to illustrate in general how neuron cells communicate with each other and how a neurotransmitter sends a signal from one neuron to another.

Some people with depression have a shortage of serotonin, the "mood" neurotransmitter in the brain. The antidepressant Prozac®, a Selective Serotonin Reuptake Inhibitor (SSRI), can help correct this imbalance by increasing the brain's own supply of serotonin.

This animation shows how Prozac® acts as a selective inhibitor of Serotonin Reuptake Transporter Protein, thus alleviating depression. In the brain, serotonin is associated with transmission of thoughts and feelings. In a healthy person, an optimal concentration of serotonin is available at the synapse. The imbalance of this neurotransmitter triggers emotional symptoms, like depressed mood, or physical symptoms, like aches and pains.

The blue colored layers represent the trans-membrane structure of both pre- and post-synaptic areas (the upper and lower part of the screen, respectively). Red colored masses in the post-synaptic membrane represent serotonin receptors. There are other membrane proteins as well. Depression can occur when the serotonin transporter protein (a G-protein coupled receptor; shown in white in the pre-synaptic membrane) takes up a serotonin molecule before it has a chance to bind to the post-synaptic receptor. This process is known as reuptake. Prozac® blocks the reuptake of serotonin by disabling the transporter proteins. Consequently, more serotonin molecules will be available to the post-synaptic receptor and thus depression is relieved.

Action of Epinephrine

2012-01-10T16:57:00.000+05:30

Epinephrine is a hormone and neurotransmitter.It is catecholomine, a sympathomimetic monoamine derived from the amino acids phenylalanine and tryosine,Epinephrine is often shortened to epi or to EP in American medical jargon.It is also referred to as adrenaline Epinephrine is a "fight or flight" hormone, and plays a central role in the short-term stress reaction. It is released from the adrenal glands when danger threatens or in an emergency. Such triggers may be threatening, exciting, or environmental stressor conditions such as high noise levels, or bright light and high ambient temperature

Subscribe in a reader

Action of Epinephrine

Epinephrine is one of many hormones that is water soluble(hydrophilic) and therefore unable to cross the hydrophobic plasma membranes of its target cells.Instead it binds to receptor proteins located in the plasma membrane and does not enter the cell.

when Epinephrine binds to beta-adrenergic receptors on teh liver cell, G proteins on the inner side of the cell membrane are activated.Each G protein is composed to three subunits and the binding of epinephrine to its receptor protein causes one of the G protein subunits to dissociate from the other two.

The G protein subunit which dissociates from the others carries a GDP,which is replaced by GTP when the subunit is activated

The activated G protein subunit then diffuses within the plasma membrane until it encounters adenylyl cyclase, a membrane enzyme that is inactive until it interacts with the G protein subunit.

When activated by the G protein subunit,adenylyl cyclase that formation of cAMP from ATP.The cAMP formed at the inner surface of the membrane diffuses within the cytoplasm,where it binds to and activates protein kinase-A, An enzyme that adds phosphate groups to specific cellular proteins.

In liver cells, protein kinase-A phosphorylates and thereby activates another enzyme called phosphorylase,which converts glycogen into glucose-6-phosphate.The glucose-6-phosphate is then converted to glucose.

Through this multistage mechanism,epinephrine causes the liver to secrete glucose into the blood during the fight-or-flight reaction.

Epinephrine is used as a drug to treat cardiac arrest and other cardiac dysrhythmias resulting in diminished or absent cardiac output; its action is to increase peripheral resistance via α1-adrenoceptor vasoconstriction, so that blood is shunted to the body's core, and the β1-adrenoceptor response which is increased cardiac rate and output (the speed and pronouncement of heart beats). This beneficial action comes with a significant negative consequence—increased cardiac irritability—which may lead to additional complications immediately following an otherwise successful resuscitation. Alternatives to this treatment include vasopressin, a powerful antidiuretic which also increases peripheral vascular resistance leading to blood shunting via vasoconstriction, but without the attendant increase in myocardial irritability.

Due to its suppressive effect on the immune system, epinephrine is the drug of choice for treating anaphylaxis. It is also useful in treating sepsis. Allergy patients undergoing immunotherapy may receive an epinephrine rinse before the allergen extract is administered, thus reducing the immune response to the administered allergen. It is also used as a bronchodilator for asthma if specific beta2-adrenergic receptor agonists are unavailable or ineffective.

Because of various expression of α1 or β2-receptors, depending on the patient, administration of epinephrine may raise or lower blood pressure, depending whether or not the net increase or decrease in peripheral resistance can balance the positive inotropic and chronotropic effects of epinephrine on the heart, effects which respectively increase the contractility and rate of the heart.

Kinesin Transport Protein

2012-01-10T16:48:00.000+05:30

Kinesins are a class of motor proteins found in eukaryotic cells.This protein is coded by KIF1B(Kinesin family member 1B)gene. Kinesins move along microtubule cables powered by the hydrolysis of ATP (thus kinesins are ATPases). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cargo such as axonal transport.

Subscribe in a reader

In the cell, small molecules such as gases and glucose diffuse to where they are needed. Large molecules synthesised in the cell body, intracellular components such as vesicles, and organelles such as mitochondria are too large (and the cytosol too crowded) to diffuse to their destinations. Motor proteins fulfill the role of transporting large cargo about the cell to their required destinations. Kinesins are motor proteins that transport such cargo by walking unidirectionally along microtubule tracks hydrolysing one molecule of adenosine triphosphate (ATP) at each step. It was thought that ATP hydrolysis powered each step, the energy released propelling the head forwards to the next binding site. It now seems that the head diffuses forward and the force of binding to the microtubule is what pulls the cargo along.

Motor proteins travel in a specific direction along a microtubule. This is because the microtubule is polar and the heads only bind to the microtubule in one orientation, while ATP binding gives each step its direction through a process known as neck linker zippering.

Most kinesins walk towards the positive end of a microtubule which, in most cells, entails transporting cargo from the centre of the cell towards the periphery. This form of transport is known as anterograde transport.

A different type of motor protein known as dyneins, move towards the minus end of the microtubule. Thus they transport cargo from the periphery (terminal buttons) of the cell towards the centre (soma). This is known as retrograde transport. Anterograde axoplasmic transport is the fastest of the two transports, moving at a speed of up to 500 mm per day, while retrograde transport moves about half as fast.

Kinesin accomplishes transport by "walking" along a microtubule. Two mechanisms have been proposed to account for this movement.

In the "hand-over-hand" mechanism, the kinesin heads step past one another, alternating the lead position.
In the "inchworm" mechanism, one kinesin head always leads, moving forward a step before the trailing head catches up.

Progeria syndrome

2012-01-10T16:47:00.000+05:30

Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not disrupt intellectual development or the development of motor skills such as sitting, standing, and walking.

Subscribe in a reader

Hutchinson-Gilford Progeria syndrome is an extremely rare condition in which physical aspects of aging are greatly accelerated, and few affected children live past age 13. About 1 in 8 million babies are born with this condition. It is a genetic condition, but occurs sporadically and is usually not inherited in families.progeria syndrome is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The condition results from new mutations in the LMNA gene, and almost always occurs in people with no history of the disorder in their family.

Causes

Mutaion is LMNA gene causes Progeria syndrome,LMNA is a gene which povides instruction to make a parotein called Lamin A,Lamin A protein plays important role in determining the shape of the nuclues within cells,It si essential component for nuclear envelope,Mutationsin this gene causes abnormal version of lamin A protein,This altered protein makes teh nuclear envelope unstable and progressively damages the nuclues,making cells more likely to die Prematurely.

WBC Apoptosis

2012-01-05T00:40:00.000+05:30

Concussions animation

2012-01-04T16:32:00.000+05:30

Every year, millions of people in the U.S. sustain head and brain injuries. Some are minor because the skull is quite good at protecting the brain. More than half are bad enough that people must go to the hospital. Serious head injuries can lead to permanent brain damage or death.

Symptoms of minor head injuries usually go away without treatment. Serious head injuries need emergency treatment. Clues that a head injury may be serious include

Aneurysms Animation

2012-01-03T09:10:00.001+05:30

A cerebral aneurysm (also known as an intracranial or intracerebral aneurysm) is a weak or thin spot on a blood vessel in the brain that balloons out and fills with blood. The bulging aneurysm can put pressure on a nerve or surrounding brain tissue. It may also leak or rupture, spilling blood into the surrounding tissue (called a hemorrhage). Some cerebral aneurysms, particularly those that are very small, do not bleed or cause other problems. Cerebral aneurysms can occur anywhere in the brain, but most are located along a loop of arteries that run between the underside of the brain and the base of the skull.

Subscribe in a reader

Most cerebral aneurysms are congenital, resulting from an inborn abnormality in an artery wall. Cerebral aneurysms are also more common in people with certain genetic diseases, such as connective tissue disorders and polycystic kidney disease, and certain circulatory disorders, such as arteriovenous malformations.

Other causes include trauma or injury to the head, high blood pressure, infection, tumors, atherosclerosis (a blood vessel disease in which fats build up on the inside of artery walls) and other diseases of the vascular system, cigarette smoking, and drug abuse. Some investigators have speculated that oral contraceptives may increase the risk of developing aneurysms.

Aneurysms that result from an infection in the arterial wall are called mycotic aneurysms. Cancer-related aneurysms are often associated with primary or metastatic tumors of the head and neck. Drug abuse, particularly the habitual use of cocaine, can inflame blood vessels and lead to the development of brain aneurysms.

Text Source: NINDS

How Proteins Fold

2012-01-03T09:08:00.000+05:30

The amino-acid sequence (or primary structure) of a protein predisposes it towards its native conformation or conformations. It will fold spontaneously during or after synthesis. While these macromolecules may be regarded as "folding themselves", the mechanism depends equally on the characteristics of the cytosol, including the nature of the primary solvent (water or lipid), macromolecular crowding, the concentration of salts, the temperature, and molecular chaperones.

Subscribe in a reader

Most folded proteins have a hydrophobic core in which side chain packing stabilizes the folded state, and charged or polar side chains on the solvent-exposed surface where they interact with surrounding water molecules. It is generally accepted that minimizing the number of hydrophobic side-chains exposed to water is the principal driving force behind the folding process, although a recent theory has been proposed which reassesses the contributions made by hydrogen bonding The strengths of hydrogen bonds in a protein vary, i.e. they are dependent on their microenvironment, thus H-bonds enveloped in a hydrophobic core contribute more than H-bonds exposed to the aqueous environment to the stability of the native state.

The process of folding in vivo often begins co-translationally, so that the N-terminus of the protein begins to fold while the C-terminal portion of the protein is still being synthesized by the ribosome. Specialized proteins called chaperones assist in the folding of other proteins. A well studied example is the bacterial GroEL system, which assists in the folding of globular proteins. In eukaryotic organisms chaperones are known as heat shock proteins. Although most globular proteins are able to assume their native state unassisted, chaperone-assisted folding is often necessary in the crowded intracellular environment to prevent aggregation; chaperones are also used to prevent misfolding and aggregation which may occur as a consequence of exposure to heat or other changes in the cellular environment.

Coronary Atherosclerosis

2012-01-03T08:57:00.000+05:30

Arteriosclerosis is a cardiovascular disease, Thickening and loss of elasticity of the coronary arteries leads to a progressive insuffiency of the artheries,plaque builds up in the coronary arteries. These arteries supply oxygen-rich blood to your heart. When blood flow to your heart is reduced or blocked, it can lead to chest pain and heart attack. CAD also is called heart disease, and it's the leading cause of death in the United States.

Arteriosclerosis is a disease in which the fatty materials is deposited on the wall of the artery, normally walls on the artery was smooth allowing blood to flow blood un-pleted ,however if damaged occurs to interlining ,Fat ,cholesterol platelets other substances may accumulate in damaged section of the arterial wall, eventually the tissue buildup up and plaque is formed narrowing the lumen of the artery ,when narrowing is severe there is risk vessel becoming blocked completely ,If the thrombus formed is diseased segment

Stem Cells: Seeds of Hope

2012-01-02T10:09:00.002+05:30

Embryonic stem cells (ES cells) are stem cells derived from the inner cell mass of an early stage embryo known as a blastocyst. Human embryos reach the blastocyst stage 4-5 days post fertilization, at which time they consist of 50-150 cells.
Subscribe in a reader

Proton pump inhibitors Therapy

2012-01-02T09:57:00.000+05:30

Proton pump inhibitors (or "PPI"s) are a group of drugs whose main action is pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H2-receptor antagonists. These drugs are among the most widely-selling drugs in the world as a result of their outstanding efficacy and safety. Structurally, the vast majority of these drugs are benzimidazole derivatives; however, promising new research indicates that imidazopyridine derivatives may be a more effective means of treatment.

Subscribe in a reader
Mechanism of action

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or more commonly just gastric proton pump) of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.

Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.

The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the pain from indigestion and heartburn, which can be exacerbated by stomach acid. However, lack of stomach acid may also contribute to hypochlorhydria, a lack of sufficient hydrochloric acid, or HCl. Hydrochloric acid is required for absorption of nutrients, particularly calcium.

The proton pump inhibitors are given in an inactive form. The inactive form is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) that have acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it.

Adverse effects

Proton pump inhibitors are generally well tolerated, and the incidence of short-term adverse effects is relatively uncommon. The range and occurrence of adverse effects are similar for all of the proton pump inhibitors, though they have been reported more frequently with omeprazole. This may be due to its longer availability and hence clinical experience.

Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, dizziness.

Infrequent adverse effects include: rash, itch, flatulence, constipation. Decreased cyanocobalamin (vitamin B12) absorption may occur with long-term use. Rarely PPI cause ‘idiosyncratic’ reactions such as erythema multiforme, pancreatitis, Stevens Johnson syndrome and acute interstitial nephritis.

It has been observed that gastric acid suppression, using H2-receptor antagonists and proton pump inhibitors, is associated with an increased risk of community-acquired pneumonia. It is suspected that acid suppression results in insufficient elimination of pathogenic organisms. It has therefore been suggested that patients at higher risk of pneumonia should only be prescribed proton pump inhibitors at lower doses and only when necessary.

PPIs have also been shown to raise risk of C. dif infection.

Long-term use of proton pump inhibitors has been less studied. But in a study of 135,000 people 50 or older, those taking high doses of PPIs for longer than one year have been found to be 2.6 times more likely to break a hip. Those taking smaller doses for 1 to 4 years were 1.2 to 1.6 times more likely to break a hip. The risk of a fracture increased with the length of time taking PPIs. Theories as to the cause of the increase are the possibility that the reduction of stomach acid reduces the amount of calcium dissolved in the stomach or that PPIs may interfere with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts

Regenerative Medicine: What Is It?

2012-01-02T09:38:00.000+05:30

Dr. Michael Longaker, Director or Children's Surgical Research, explains how regenerative, reparative, replacement and tissue engineering medicine represent an emerging field that holds great promise for core problems in medicine world wide.

PCR

2012-01-02T09:11:00.000+05:30

Polymerase chain reaction (PCR) is a technique widely used in molecular biology. It derives its name from one of its key components, a DNA polymerase used to amplify a piece of DNA by in vitro enzymatic replication. As PCR progresses, the DNA thus generated is itself used as template for replication. This sets in motion a chain reaction in which the DNA template is exponentially amplified. With PCR it is possible to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating millions or more copies of the DNA piece. PCR can be extensively modified to perform a wide array of genetic manipulations.

Subscribe in a reader

Almost all PCR applications employ a heat-stable DNA polymerase, such as Taq polymerase, an enzyme originally isolated from the bacterium Thermus aquaticus. This DNA polymerase enzymatically assembles a new DNA strand from DNA building blocks, the nucleotides, using single-stranded DNA as template and DNA oligonucleotides (also called DNA primers) required for initiation of DNA synthesis. The vast majority of PCR methods use thermal cycling, i.e., alternately heating and cooling the PCR sample to a defined series of temperature steps. These thermal cycling steps are necessary to physically separate the strands (at high temperatures) in a DNA double helix (DNA melting) used as template during DNA synthesis (at lower temperatures) by the DNA polymerase to selectively amplify the target DNA. The selectivity of PCR results from the use of primers that are complementary to the DNA region targeted for amplification under specific thermal cycling conditions.

Developed in 1983 by Kary Mullis, PCR is now a common and often indispensable technique used in medical and biological research labs for a variety of applications.These include DNA cloning for sequencing, DNA-based phylogeny, or functional analysis of genes; the diagnosis of hereditary diseases; the identification of genetic fingerprints (used in forensic sciences and paternity testing); and the detection and diagnosis of infectious diseases.

PCR principles and procedure

PCR is used to amplify specific regions of a DNA strand (the DNA target). This can be a single gene, a part of a gene, or a non-coding sequence. Most PCR methods typically amplify DNA fragments of up to 10 kilo base pairs (kb), although some techniques allow for amplification of fragments up to 40 kb in size.

A basic PCR set up requires several components and reagents. These components include:

DNA template that contains the DNA region (target) to be amplified.
Two primers, which are complementary to the DNA regions at the 5' (five prime) or 3' (three prime) ends of the DNA region.
A DNA polymerase such as Taq polymerase or another DNA polymerase with a temperature optimum at around 70°C.
Deoxynucleoside triphosphates (dNTPs; also very commonly and erroneously called deoxynucleotide triphosphates), the building blocks from which the DNA polymerases synthesizes a new DNA strand.
Buffer solution, providing a suitable chemical environment for optimum activity and stability of the DNA polymerase.
Divalent cations, magnesium or manganese ions; generally Mg2+ is used, but Mn2+ can be utilized for PCR-mediated DNA mutagenesis, as higher Mn2+ concentration increases the error rate during DNA synthesis.
Monovalent cation potassium ions.

The PCR is commonly carried out in a reaction volume of 20-150 μl in small reaction tubes (0.2-0.5 ml volumes) in a thermal cycler. The thermal cycler heats and cools the reaction tubes to achieve the temperatures required at each step of the reaction (see below). Many modern thermal cyclers make use of the Peltier effect which permits both heating and cooling of the block holding the PCR tubes simply by reversing the electric current. Thin-walled reaction tubes permit favorable thermal conductivity to allow for rapid thermal equilibration. Most thermal cyclers have heated lids to prevent condensation at the top of the reaction tube. Older thermocyclers lacking a heated lid require a layer of oil on top of the reaction mixture or a ball of wax inside the tube.

Procedure

The PCR usually consists of a series of 20 to 40 repeated temperature changes called cycles; each cycle typically consists of 2-3 discrete temperature steps. Most commonly PCR is carried out with cycles that have three temperature steps (Fig. 2). The cycling is often preceded by a single temperature step (called hold) at a high temperature (>90°C), and followed by one hold at the end for final product extension or brief storage. The temperatures used and the length of time they are applied in each cycle depend on a variety of parameters. These include the enzyme used for DNA synthesis, the concentration of divalent ions and dNTPs in the reaction, and the melting temperature (Tm) of the primers.

Initialization step: This step consists of heating the reaction to a temperature of 94-96°C (or 98°C if extremely thermostable polymerases are used), which is held for 1-9 minutes. It is only required for DNA polymerases that require heat activation by hot-start PCR.
Denaturation step: This step is the first regular cycling event and consists of heating the reaction to 94-98°C for 20-30 seconds. It causes melting of DNA template and primers by disrupting the hydrogen bonds between complementary bases of the DNA strands, yielding single strands of DNA.
Annealing step: The reaction temperature is lowered to 50-65°C for 20-40 seconds allowing annealing of the primers to the single-stranded DNA template. Typically the annealing temperature is about 3-5 degrees Celsius below the Tm of the primers used. Stable DNA-DNA hydrogen bonds are only formed when the primer sequence very closely matches the template sequence. The polymerase binds to the primer-template hybrid and begins DNA synthesis.
Extension/elongation step: The temperature at this step depends on the DNA polymerase used; Taq polymerase has its optimum activity temperature at 75-80°C, and commonly a temperature of 72°C is used with this enzyme. At this step the DNA polymerase synthesizes a new DNA strand complementary to the DNA template strand by adding dNTPs that are complementary to the template in 5' to 3' direction, condensing the 5'-phosphate group of the dNTPs with the 3'-hydroxyl group at the end of the nascent (extending) DNA strand. The extension time depends both on the DNA polymerase used and on the length of the DNA fragment to be amplified. As a rule-of-thumb, at its optimum temperature, the DNA polymerase will polymerize a thousand bases per minute. Under optimum conditions, i.e., if there are no limitations due to limiting substrates or reagents, at each extension step, the amount of DNA target is doubled, leading to exponential (geometric) amplification of the specific DNA fragment.
Final elongation: This single step is occasionally performed at a temperature of 70-74°C for 5-15 minutes after the last PCR cycle to ensure that any remaining single-stranded DNA is fully extended.
Final hold: This step at 4-15°C for an indefinite time may be employed for short-term storage of the reaction.

To check whether the PCR generated the anticipated DNA fragment (also sometimes referred to as the amplimer or amplicon), agarose gel electrophoresis is employed for size separation of the PCR products. The size(s) of PCR products is determined by comparison with a DNA ladder (a molecular weight marker), which contains DNA fragments of known size, run on the gel alongside the PCR products

PCR stages

The PCR process can be divided into three stages:

Exponential amplification: At every cycle, the amount of product is doubled (assuming 100% reaction efficiency). The reaction is very specific and precise.
Levelling off stage: The reaction slows as the DNA polymerase loses activity and as consumption of reagents such as dNTPs and primers causes them to become limiting.
Plateau: No more product accumulates due to exhaustion of reagents and enzyme.

PCR optimization

In practice, PCR can fail for various reasons, in part due to its sensitivity to contamination causing amplification of spurious DNA products. Because of this, a number of techniques and procedures have been developed for optimizing PCR conditions. Contamination with extraneous DNA is addressed with lab protocols and procedures that separate pre-PCR mixtures from potential DNA contaminants. This usually involves spatial separation of PCR-setup areas from areas for analysis or purification of PCR products, and thoroughly cleaning the work surface between reaction setups. Primer-design techniques are important in improving PCR product yield and in avoiding the formation of spurious products, and the usage of alternate buffer components or polymerase enzymes can help with amplification of long or otherwise problematic regions of DNA.

Application of PCR Isolation of genomic DNA

PCR allows isolation of DNA fragments from genomic DNA by selective amplification of a specific region of DNA. This use of PCR augments many methods, such as generating hybridization probes for Southern or northern hybridization and DNA cloning, which require larger amounts of DNA, representing a specific DNA region. PCR supplies these techniques with high amounts of pure DNA, enabling analysis of DNA samples even from very small amounts of starting material.

Other applications of PCR include DNA sequencing to determine unknown PCR-amplified sequences in which one of the amplification primers may be used in Sanger sequencing, isolation of a DNA sequence to expedite recombinant DNA technologies involving the insertion of a DNA sequence into a plasmid or the genetic material of another organism. Bacterial colonies (E.coli) can be rapidly screened by PCR for correct DNA vector constructs. PCR may also be used for genetic fingerprinting; a forensic technique used to identify a person or organism by comparing experimental DNAs through different PCR-based methods.

Some PCR 'fingerprints' methods have high discriminative power and can be used to identify genetic relationships between individuals, such as parent-child or between siblings, and are used in paternity testing . This technique may also be used to determine evolutionary relationships among organisms.

Amplification and quantitation of DNA

Because PCR amplifies the regions of DNA that it targets, PCR can be used to analyze extremely small amounts of sample. This is often critical for forensic analysis, when only a trace amount of DNA is available as evidence. PCR may also be used in the analysis of ancient DNA that is thousands of years old. These PCR-based techniques have been successfully used on animals, such as a forty-thousand-year-old mammoth, and also on human DNA, in applications ranging from the analysis of Egyptian mummies to the identification of a Russian Tsar.

Quantitative PCR methods allow the estimation of the amount of a given sequence present in a sample – a technique often applied to quantitatively determine levels of gene expression. Real-time PCR is an established tool for DNA quantification that measures the accumulation of DNA product after each round of PCR amplification.

PCR in diagnosis of diseases

PCR allows early diagnosis of malignant diseases such as leukemia and lymphomas, which is currently the highest developed in cancer research and is already being used routinely. PCR assays can be performed directly on genomic DNA samples to detect translocation-specific malignant cells at a sensitivity which is at least 10,000 fold higher than other methods.

PCR also permits identification of non-cultivatable or slow-growing microorganisms such as mycobacteria, anaerobic bacteria, or viruses from tissue culture assays and animal models. The basis for PCR diagnostic applications in microbiology is the detection of infectious agents and the discrimination of non-pathogenic from pathogenic strains by virtue of specific genes.

Viral DNA can likewise be detected by PCR. The primers used need to be specific to the targeted sequences in the DNA of a virus, and the PCR can be used for diagnostic analyses or DNA sequencing of the viral genome. The high sensitivity of PCR permits virus detection soon after infection and even before the onset of disease. Such early detection may give physicians a significant lead in treatment. The amount of virus ("viral load") in a patient can also be quantified by PCR-based DNA quantitation techniques.

Variations on the basic PCR technique

Allele-specific PCR: This diagnostic or cloning technique is used to identify or utilize single-nucleotide polymorphisms (SNPs) (single base differences in DNA). It requires prior knowledge of a DNA sequence, including differences between alleles, and uses primers whose 3' ends encompass the SNP. PCR amplification under stringent conditions is much less efficient in the presence of a mismatch between template and primer, so successful amplification with an SNP-specific primer signals presence of the specific SNP in a sequence.
Assembly PCR or Polymerase Cycling Assembly (PCA): Assembly PCR is the artificial synthesis of long DNA sequences by performing PCR on a pool of long oligonucleotides with short overlapping segments. The oligonucleotides alternate between sense and antisense directions, and the overlapping segments determine the order of the PCR fragments thereby selectively producing the final long DNA product.
Asymmetric PCR: Asymmetric PCR is used to preferentially amplify one strand of the original DNA more than the other. It finds use in some types of sequencing and hybridization probing where having only one of the two complementary stands is required. PCR is carried out as usual, but with a great excess of the primers for the chosen strand. Due to the slow (arithmetic) amplification later in the reaction after the limiting primer has been used up, extra cycles of PCR are required. A recent modification on this process, known as Linear-After-The-Exponential-PCR (LATE-PCR), uses a limiting primer with a higher melting temperature (Melting temperature|Tm) than the excess primer to maintain reaction efficiency as the limiting primer concentration decreases mid-reaction.
Helicase-dependent amplification: This technique is similar to traditional PCR, but uses a constant temperature rather than cycling through denaturation and annealing/extension cycles. DNA Helicase, an enzyme that unwinds DNA, is used in place of thermal denaturation.
Hot-start PCR: This is a technique that reduces non-specific amplification during the initial set up stages of the PCR. The technique may be performed manually by heating the reaction components to the melting temperature (e.g., 95˚C) before adding the polymerase. Specialized enzyme systems have been developed that inhibit the polymerase's activity at ambient temperature, either by the binding of an antibody or by the presence of covalently bound inhibitors that only dissociate after a high-temperature activation step. Hot-start/cold-finish PCR is achieved with new hybrid polymerases that are inactive at ambient temperature and are instantly activated at elongation temperature.
Intersequence-specific (ISSR) PCR: a PCR method for DNA fingerprinting that amplifies regions between some simple sequence repeats to produce a unique fingerprint of amplified fragment lengths.
Inverse PCR: a method used to allow PCR when only one internal sequence is known. This is especially useful in identifying flanking sequences to various genomic inserts. This involves a series of DNA digestions and self ligation, resulting in known sequences at either end of the unknown sequence.
Ligation-mediated PCR: This method uses small DNA linkers ligated to the DNA of interest and multiple primers annealing to the DNA linkers; it has been used for DNA sequencing, genome walking, and DNA footprinting.
Methylation-specific PCR (MSP): The MSP method was developed by Stephen Baylin and Jim Herman at the Johns Hopkins School of Medicine,and is used to detect methylation of CpG islands in genomic DNA. DNA is first treated with sodium bisulfite, which converts unmethylated cytosine bases to uracil, which is recognized by PCR primers as thymine. Two PCRs are then carried out on the modified DNA, using primer sets identical except at any CpG islands within the primer sequences. At these points, one primer set recognizes DNA with cytosines to amplify methylated DNA, and one set recognizes DNA with uracil or thymine to amplify unmethylated DNA. MSP using qPCR can also be performed to obtain quantitative rather than qualitative information about methylation.
Miniprimer PCR: Miniprimer PCR uses a novel thermostable polymerase (S-Tbr) that can extend from short primers ("smalligos") as short as 9 or 10 nucleotides, instead of the approximately 20 nucleotides required by Taq. This method permits PCR targeting smaller primer binding regions, and is particularly useful to amplify unknown, but conserved, DNA sequences, such as the 16S (or eukaryotic 18S) rRNA gene. 16S rRNA miniprimer PCR was used to characterize a microbial mat community growing in an extreme environment, a hypersaline pond in Puerto Rico. In that study, deeply divergent sequences were discovered with high frequency and included representatives that deﬁned two new division-level taxa, suggesting that miniprimer PCR may reveal new dimensions of microbial diversity. By enlarging the "sequence space" that may be queried by PCR primers, this technique may enable novel PCR strategies that are not possible within the limits of primer design imposed by Taq and other commonly used enzymes.
Multiplex Ligation-dependent Probe Amplification (MLPA): permits multiple targets to be amplified with only a single primer pair, thus avoiding the resolution limitations of multiplex PCR (see below).
Multiplex-PCR: The use of multiple, unique primer sets within a single PCR mixture to produce amplicons of varying sizes specific to different DNA sequences. By targeting multiple genes at once, additional information may be gained from a single test run that otherwise would require several times the reagents and more time to perform. Annealing temperatures for each of the primer sets must be optimized to work correctly within a single reaction, and amplicon sizes, i.e., their base pair length, should be different enough to form distinct bands when visualized by gel electrophoresis.
Nested PCR: increases the specificity of DNA amplification, by reducing background due to non-specific amplification of DNA. Two sets of primers are being used in two successive PCRs. In the first reaction, one pair of primers is used to generate DNA products, which besides the intended target, may still consist of non-specifically amplified DNA fragments. The product(s) are then used in a second PCR with a set of primers whose binding sites are completely or partially different from and located 3' of each of the primers used in the first reaction. Nested PCR is often more successful in specifically amplifying long DNA fragments than conventional PCR, but it requires more detailed knowledge of the target sequences.
Overlap-extension PCR: is a genetic engineering technique allowing the construction of a DNA sequence with an alteration inserted beyond the limit of the longest practical primer length.
Quantitative PCR (Q-PCR): is used to measure the quantity of a PCR product (preferably real-time). It is the method of choice to quantitatively measure starting amounts of DNA, cDNA or RNA. Q-PCR is commonly used to determine whether a DNA sequence is present in a sample and the number of its copies in the sample. The method with currently the highest level of accuracy is Quantitative real-time PCR. It is often confusingly known as RT-PCR (Real Time PCR) or RQ-PCR. QRT-PCR or RTQ-PCR are more appropriate contractions. RT-PCR commonly refers to reverse transcription PCR (see below), which is often used in conjunction with Q-PCR. QRT-PCR methods use fluorescent dyes, such as Sybr Green, or fluorophore-containing DNA probes, such as TaqMan, to measure the amount of amplified product in real time.
RT-PCR: (Reverse Transcription PCR) is a method used to amplify, isolate or identify a known sequence from a cellular or tissue RNA. The PCR is preceded by a reaction using reverse transcriptase to convert RNA to cDNA. RT-PCR is widely used in expression profiling, to determine the expression of a gene or to identify the sequence of an RNA transcript, including transcription start and termination sites and, if the genomic DNA sequence of a gene is known, to map the location of exons and introns in the gene. The 5' end of a gene (corresponding to the transcription start site) is typically identified by an RT-PCR method, named RACE-PCR, short for Rapid Amplification of cDNA Ends.
Solid Phase PCR: encompasses multiple meanings, including Polony Amplification (where PCR colonies are derived in a gel matrix, for example), 'Bridge PCR' (the only primers present are covalently linked to solid support surface), conventional Solid Phase PCR (where Asymmetric PCR is applied in the presence of solid support bearing primer with sequence matching one of the aqueous primers) and Enhanced Solid Phase PCR(where conventional Solid Phase PCR can be improved by employing high Tm solid support primer with application of a thermal 'step' to favour solid support priming).
TAIL-PCR: Thermal asymmetric interlaced PCR is used to isolate unknown sequence flanking a known sequence. Within the known sequence TAIL-PCR uses a nested pair of primers with differing annealing temperatures; a degenerate primer is used to amplify in the other direction from the unknown sequence.
Touchdown PCR: a variant of PCR that aims to reduce nonspecific background by gradually lowering the annealing temperature as PCR cycling progresses. The annealing temperature at the initial cycles is usually a few degrees (3-5˚C) above the Tm of the primers used, while at the later cycles, it is a few degrees (3-5˚C) below the primer Tm. The higher temperatures give greater specificity for primer binding, and the lower temperatures permit more efficient amplification from the specific products formed during the initial cycles.
PAN-AC: This method uses isothermal conditions for amplification, and may be used in living cells.
Universal Fast Walking: this method allows genome walking and genetic fingerprinting using a more specific 'two-sided' PCR than conventional 'one-sided' approaches (using only one gene-specific primer and one general primer - which can lead to artefactual 'noise') by virtue of a mechanism involving lariat structure formation. Streamlined derivatives of UFW are LaNe RAGE (lariat-dependent nested PCR for rapid amplification of genomic DNA ends) , 5'RACE LaNe and 3'RACE LaNe .

Human Embryonic Stems Cells Lecture

2012-01-02T09:09:00.000+05:30

Julie Baker, Assistant Professor of Genetics and Hank Greely, Professor of Law and Genetics discuss human embryonic stem cells, one of the most promising, most complicated and most controversial areas of contemporary biomedical research.

How Cranberry Juice Prevents Urinary Tract Infections

2012-01-02T09:08:00.000+05:30

Cranberry juice also has been shown to have positive effects on UTIs.cranberry juice produces hippuric acid in the urine which acidifies the urine and prevents bacteria from sticking to the walls of the bladder

Nervous system

2012-01-02T09:06:00.000+05:30

The nervous system is a highly specialized network whose principal components are nerves called neurons. Neurons are interconnected to each other in complex arrangements and have the property of conducting, using electrochemical signals, and a great variety of stimuli both within the nervous tissue as well as from and towards most of the other tissues. Thus, neurons coordinate multiple functions in organisms. Nervous systems are found in many multicellular animals but differ greatly in complexity between species.

Subscribe in a reader

The human nervous system can be grouped into both with gross anatomy, (which describes the parts that are large enough to be seen with the naked eye,) and microanatomy, (which describes the system at a cellular level.) At gross anatomy, the nervous system can be grouped in distinct organs, these being actually stations which the neural pathways cross through. Thus, with a didactical purpose, these organs, according to their ubication, can be divided in two parts: the central nervous system (CNS) and the peripheral nervous system (PNS).

Central nervous system

The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. The CNS is contained within the dorsal cavity, with the brain within the cranial cavity, and the spinal cord in the spinal cavity. The CNS is covered by the meninges. The brain is also protected by the skull, and the spinal cord is also protected by the vertebrae. The nervous system can be connected into many systems that can function together. The two systems are central nervous system (CNS) and the peripheral nervous system (PNS).

Peripheral nervous system

The PNS consists of all the other nervous structures that do not lie in the CNS. The large majority of what are commonly called nerves (which are actually axonal processes of nerve cells) are considered to be PNS.

Microanatomy

The nervous system is, on a small scale, primarily made up of neurons. However, glial cells also play a major role.

Neurons

ey are the core components of both the central nervous system & peripheral nervous system. Neurons are sensors that send electric messages to the Central Nervous System which send the electric messages back to the neurons telling them how to react, where the messages are finally sent back directly to the brain. These messages travel at a usual pace of 100 meters per second.The neuron is the fundamental unit of the nervous system, particularly the brain

Glial cells

Glial cells are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. In the human brain, glia are estimated to outnumber neurons by about 10 to 1.

Glial cells provide support and protection for neurons. They are thus known as the "glue" of the nervous system. The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons.

Cardiac Arrhythmia Animation

2012-01-02T09:03:00.000+05:30

Cardiac arrhythmia (also dysrhythmia) is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular. Some arrhythmias are life-threatening medical emergencies that can result in cardiac arrest and sudden death. Others cause aggravating symptoms such as an abnormal awareness of heart beat (palpitations), and may be merely annoying. Others may not be associated with any symptoms at all, but pre-dispose toward potentially life threatening stroke or embolus.

Subscribe in a reader

The term cardiac arrhythmia covers a very large number of very different conditions, many of which receive separate articles in depth elsewhere in Wikipedia. The most common symptom of arrhythmia is an abnormal awareness of heartbeat, termed palpitations. These may be infrequent, frequent, or continuous. Some of these arrhythmias are harmless (though annoying) but many of them predispose to adverse outcomes. Some arrhythmias do not cause symptoms, and are not associated with increased mortality. However, some asymptomatic arrhythmias are associated with adverse events. Examples include increase in risk of blood clotting within the heart, and also an insufficient amount of blood is transported to the heart beacause of weak heart beat, and thus increase the risk of embolisation and stroke, or increase in the risk of heart failure, or increase in the risk of sudden cardiac death.

Some arrhythmias are very minor and can be regarded as variants of normal. In fact, most people will sometimes feel their heart skip a beat, or give an occasional extra strong beat - neither of which is usually a cause for alarm. The term sinus arrhythmia refers to a normal phenomenon of mild acceleration and slowing of the heart rate that occurs with breathing in and out. It is usually quite pronounced in children, and steadily lessens with age.

If an arrhythmia results in a heart beat that is too fast, too slow or too weak to supply the body's needs, this manifests as a lower blood pressure and may cause lightheadedness or dizziness, or fainting. Some types of arrhythmia result in cardiac arrest, or sudden death. Medical assessment of the abnormality using an electrocardiogram is the best way to diagnose and assess the risk of any given arrhythmia. Mechanisms and aetiology Each heart beat originates as an electrical impulse from a small area of tissue in the right atrium of the heart called the sinus node or Sino-atrial node or SA node. The impulse initially causes both of the atria to contract, then activates the atrioventricular (or AV) node which is normally the only electrical connection between the atria and the ventricles or main pumping chambers. The impulse then spreads through both ventricles via the His Purkinje fibres causing a synchronised contraction of the heart muscle, and thus, the pulse. In adults the normal resting heart rate ranges from 60 to 100 beats per minute. The resting heart rate in children is much faster. Bradycardias A slow rhythm, (less than 60 beats/min), is labelled bradycardia. This may be caused by a slowed signal from the sinus node (termed sinus bradycardia), a pause in the normal activity of the sinus node (termed sinus arrest), or by blocking of the electrical impulse on its way from the atria to the ventricles (termed AV block or heart block). Heart block comes in varying degrees and severity. It may be caused by reversible poisoning of the AV node (with drugs that impair conduction) or by irreversible damage to the node. Tachycardias Any heart rate faster than 100 beats/minute is labelled tachycardia. Tachycardia may result in palpitation, however, tachycardia is not necessarily an arrhythmia. Increased heart rate is a normal response to physical exercise or emotional stress. This is mediated by the sympathetic nervous system on the sinus node, and is called sinus tachycardia. Other things that increase sympathetic nervous system activity in the heart include ingested or injected substances such as caffeine or amphetamines, and an overactive thyroid gland (hyperthyroidism). Tachycardia that is not sinus tachycardia usually results from the addition of abnormal impulses to the normal cardiac cycle. Abnormal impulses can begin by one of three mechanisms: automaticity, reentry or triggered activity. A specialised form of re-entry problem is termed fibrillation. Automaticity Automaticity refers to a cardiac muscle cell firing off an impulse on its own. All of the cells in the heart have the ability to initiate an action potential, however, only some of these cells are designed to routinely trigger heart beats. These cells are found in the 'conduction system' of the heart and include the SA node, AV node, Bundle of HIS and Purkinje fibers. The sinoatrial node is a single specialized location in the atrium which has a higher automaticity (a faster pacemaker) than the rest of the heart, and therefore is usually responsible for setting the heart rate, and initiating each heart beat. Any part of the heart that initiates an impulse without waiting for the sinoatrial node is called an ectopic focus, and is by definition a pathological phenomenon. This may cause a single premature beat now and then, or, if the ectopic focus fires more often than the sinoatrial node, it can produce a sustained abnormal rhythm. Rhythms produced by an ectopic focus in the atria, or by the atrioventricular node, are the least dangerous dysrhythmias; but they can still produce a decrease in the heart's pumping efficiency, because the signal reaches the various parts of the heart muscle with different timing to usual and can be responsible for poorly coordinated contraction. Conditions that increase automaticity include sympathetic nervous system stimulation and hypoxia. The resulting heart rhythm depends on where the first signal begins: if it is the sinoatrial node, the rhythm remains normal but rapid; if it is an ectopic focus, many types of dysrhythmia can result. Re-entry Re-entry dysrhythmias occur when an electrical impulse recurrently travels in a tight circle within the heart, rather than moving from one end of the heart to the other and then stopping. Every cardiac cell is able to transmit impulses in every direction, but will only do so once within a short period of time. Normally an action potential impulse will spread through the heart quickly enough that each cell will only respond once. However, if conduction is abnormally slow in some areas, part of the impulse will arrive late and potentially be treated as a new impulse. Depending on the timing, this can produce a sustained abnormal circuit rhythm. Re-entry circuits are responsible for atrial flutter, most paroxysmal supraventricular tachycardia, and dangerous ventricular tachycardia. By analogy, imagine a room full of people all given these instructions: "If you see anyone starting to stand up, then stand up for three seconds and sit back down." If the people are quick enough to respond, the first person to stand will trigger a single wave which will then die out; but if there are stragglers on one side of the room, people who have already sat down will see them and start a second wave, and so on. Fibrillation When an entire chamber of the heart is involved in a multiple micro-reentry circuits, and therefore quivering with chaotic electrical impulses, it is said to be in fibrillation. Fibrillation can affect the atrium (atrial fibrillation) or the ventricle (ventricular fibrillation); ventricular fibrillation is imminently life-threatening. Atrial fibrillation affects the upper chambers of the heart, known as the atria. Atrial fibrillation may be due to serious underlying medical conditions, and should be evaluated by a physician. It is not typically a medical emergency. Ventricular fibrillation occurs in the ventricles (lower chambers) of the heart; it is always a medical emergency. If left untreated, ventricular fibrillation (VF, or V-fib) can lead to death within minutes. When a heart goes into V-fib, effective pumping of the blood stops. V-fib is considered a form of cardiac arrest, and an individual suffering from it will not survive unless cardiopulmonary resuscitation (CPR) and defibrillation are provided immediately. CPR can prolong the survival of the brain in the lack of a normal pulse, but defibrillation is the only intervention which can restore a healthy heart rhythm. Defibrillation is performed by applying an electric shock to the heart, which resets the cells, permitting a normal beat to re-establish itself.

Triggered beats

Triggered beats occur when problems at the level of the ion channels in individual heart cells result in abnormal propagation of electrical activity and can lead to sustained abnormal rhythm. They are relatively rare, but can result from the action of anti-arrhythmic drugs.

Mass spectrometry

2012-01-02T09:00:00.001+05:30

Mass spectrometry is an analytical technique that identifies the chemical composition of a compound or sample on the basis of the mass-to-charge ratio of charged particles.The method employs chemical fragmentation of a sample into charged particles (ions) and measurements of two properties, charge and mass, of the resulting particles, the ratio of which is deduced by passing the particles through electric and magnetic fields in a mass spectrometer. The design of a mass spectrometer has three essential modules: an ion source, which transforms the molecules in a sample into ionized fragments; a mass analyzer, which sorts the ions by their masses by applying electric and magnetic fields; and a detector, which measures the value of some indicator quantity and thus provides data for calculating the abundances each ion fragment present. The technique has both qualitative and quantitative uses, such as identifying unknown compounds, determining the isotopic composition of elements in a compound, determining the structure of a compound by observing its fragmentation, quantifying the amount of a compound in a sample using carefully designed methods (e.g., by comparison with known quantities of heavy isotopes), studying the fundamentals of gas phase ion chemistry (the chemistry of ions and neutrals in vacuum), and determining other physical, chemical, or biological properties of compounds.

The word spectrograph has been used since 1884 as an "International Scientific Vocabulary". The linguistic roots, a combination and removal of bound morphemes and free morphemes, are closely related to the terms spectr-um and phot-ograph-ic plate. In fact, early spectrometry devices that measured the mass-to-charge ratio of ions were called mass spectrographs because they were instruments that recorded a spectrum of mass values on a photographic plate. A mass spectroscope is similar to a mass spectrograph except that the beam of ions is directed onto a phosphor screen.A mass spectroscope configuration was used in early instruments when it was desired that the effects of adjustments be quickly observed. Once the instrument was properly adjusted, a photographic plate was inserted and exposed. The term mass spectroscope continued to be used even though the direct illumination of a phosphor screen was replaced by indirect measurements with an oscilloscope.The use of the term mass spectroscopy is now discouraged due to the possibility of confusion with light spectroscopy. Mass spectrometry is often abbreviated as mass-spec or simply as MS. Thomson has also noted that a mass spectroscope is similar to a mass spectrograph except that the beam of ions is directed onto a phosphor screen. The suffix -scope here denotes the direct viewing of the spectra (range) of masses.

Simplified example

The following example describes the operation of a spectrometer mass analyzer, which is of the sector type. Consider a sample of sodium chloride (table salt). In the ion source, the sample is vaporized (turned into gas) and ionized (transformed into electrically charged particles) into sodium (Na+) and chloride (Cl-) ions. Sodium atoms and ions are monoisotopic, with a mass of about 23 amu. Chloride atoms and ions come in two isotopes with masses of approximately 35 amu (at a natural abundance of about 75 percent) and approximately 37 amu (at a natural abundance of about 25 percent). The analyzer part of the spectrometer contains electric and magnetic fields, which exert forces on ions traveling through these fields. The speed of a charged particle may be increased or decreased while passing through the electric field, and its direction may be altered by the magnetic field. The magnitude of the deflection of the moving ion's trajectory depends on its mass-to-charge ratio. By Newton's second law of motion, lighter ions get deflected by the magnetic force more than heavier ions. The streams of sorted ions pass from the analyzer to the detector, which records the relative abundance of each ion type. This information is used to determine the chemical element composition of the original sample (i.e. that both sodium and chlorine are present in the sample) and the isotopic composition of its constituents (the ratio of 35Cl to 37Cl).

Fourier transform ion cyclotron resonance

Fourier transform mass spectrometry, or more precisely Fourier transform ion cyclotron resonance MS, measures mass by detecting the image current produced by ions cyclotroning in the presence of a magnetic field. Instead of measuring the deflection of ions with a detector such as an electron multiplier, the ions are injected into a Penning trap (a static electric/magnetic ion trap) where they effectively form part of a circuit. Detectors at fixed positions in space measure the electrical signal of ions which pass near them over time, producing a periodic signal. Since the frequency of an ion's cycling is determined by its mass to charge ratio, this can be deconvoluted by performing a Fourier transform on the signal. FTMS has the advantage of high sensitivity (since each ion is "counted" more than once) and much higher resolution and thus precision.

Ion cyclotron resonance (ICR) is an older mass analysis technique similar to FTMS except that ions are detected with a traditional detector. Ions trapped in a Penning trap are excited by an RF electric field until they impact the wall of the trap, where the detector is located. Ions of different mass are resolved according to impact time.

Very similar nonmagnetic FTMS has been performed, where ions are electrostatically trapped in an orbit around a central, spindle shaped electrode. The electrode confines the ions so that they both orbit around the central electrode and oscillate back and forth along the central electrode's long axis. This oscillation generates an image current in the detector plates which is recorded by the instrument. The frequencies of these image currents depend on the mass to charge ratios of the ions. Mass spectra are obtained by Fourier transformation of the recorded image currents.

Gene Switch Animation

2012-01-02T08:54:00.002+05:30

Regulatory "switches" are found upstream from a gene. Regulatory molecules bind to the switches and recruit RNA polymerase to bind to the gene's promoter region, increasing the transcription of the gene into messenger RNA.

A situation in which a cell or organism stops expressing one gene orgene group and switches to expressing a different gene or group of genes.

ADHD Causes & Treatments

2012-01-02T08:47:00.000+05:30

Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral disorder. ADHD is characterized by inattention, hyperactivity and impulsive behavior. This informative video animation shows possible causes and treatments.

ADHD stands for attention deficit hyperactivity disorder. ADHD used to be known as attention deficit disorder, or ADD. In 1994, it was renamed ADHD. The term ADD is sometimes still used, though, to describe a type of ADHD that doesn't involve hyperactivity.

Subscribe in a reader

ADHD is a medical condition that affects how well someone can sit still, focus, and pay attention. People with ADHD have differences in the parts of their brains that control attention and activity. This means that they may have trouble focusing on certain tasks and subjects, or they may seem "wired," act impulsively, and get into trouble.

Symptoms and Signs of ADHD

Although ADHD begins in childhood, sometimes it's not diagnosed until a person is a teen — and occasionally not even until someone reaches adulthood.

Because ADHD is a broad category covering different things — attention, activity, and impulsivity — it can show up in different ways in different people. Some of the signs of ADHD are when someone:

has difficulty paying attention or staying focused on a task or activity
has problems finishing assignments at school or home and jumps from one activity to another
has trouble focusing on instructions and difficulty following through
loses or forgets things such as homework
is easily distracted, even when doing something fun
has problems paying close attention to details or makes careless mistakes
has trouble organizing tasks and activities
has difficulty waiting one's turn
interrupts or intrudes on other people
blurts out answers before questions have been completed
fidgets with hands or feet or squirms about when seated
feels restless
talks excessively and has trouble engaging in activities quietly

Of course, it's normal for everyone to zone out in a boring class, jump into a conversation, or leave their homework on the kitchen table once in a while. But people with ADHD have so much trouble staying focused and controlling their behavior that it affects their emotions and how well they do in school or other areas of their lives. In fact, ADHD is often viewed as a learning disorder because it can interfere so much with a person's ability to study and learn.

Sometimes the symptoms of ADHD become less severe as a person grows older. For example, experts believe that the hyperactivity part of the disorder can diminish with age, although the problems with organization and attention often remain. Although some people may "grow out of" their symptoms, more than half of all kids who have ADHD will continue to show signs of the condition as young adults.

What Causes ADHD?
Doctors and researchers still aren't exactly sure why some people have ADHD. Research shows that ADHD is probably genetic and that it may be inherited in some cases. Scientists are also exploring other things that may be associated with ADHD: For example, ADHD may be more prevalent in kids who are born prematurely. It is also more common in guys than it is in girls.

Doctors do know that ADHD is caused by changes in brain chemicals called neurotransmitters (pronounced: nur-oh-trans-mih-terz). These chemicals help send messages between nerve cells in the brain. The neurotransmitter dopamine (pronounced: doe-puh-meen), for example, stimulates the brain's attention centers. So a person with low amounts of this chemical may show symptoms of ADHD.

How Is ADHD Treated?
Because there's no cure for ADHD, doctors treat people by helping them to manage the symptoms most effectively. Because some people have more trouble with the attention side of the disorder and others have more problems with the activity side, doctors tailor their treatment to the person's symptoms. So different people with ADHD may have different treatments.

Doctors usually follow a multimodal (pronounced: mul-tee-moe-dul) approach to ADHD treatment. This means that they use several different treatment methods for one patient, such as medication, family and individual counseling, and changes at school to address particular learning styles.

Certain medicines can help people with ADHD by improving their focus and attention and reducing the impulsiveness and hyperactivity associated with ADHD. People with ADHD used to have to take medicine several times a day, but now there are some that can be taken at home once a day in the morning. Scientists are constantly working to develop new medications to treat ADHD.

You can discuss treatment options with your doctor, but always follow the doctor's instructions about medication dosages. If you have been taking medicine for ADHD since you were a kid, your doctor will probably adjust your medication for changes in your symptoms as you get older.

Family counseling helps treat ADHD because it keeps parents informed and also shows them ways they can work with their kids to help. It also helps to improve communication within the family and to solve problems that come up between teens and their parents at home. Individual counseling helps teens with ADHD to better understand their behavior and to learn coping skills. Sometimes lots of teens with ADHD work together in group therapy, which helps them work on coping skills and getting along better with others, if that's been a problem.

Schools are also involved in helping students with ADHD — most will develop a plan that's right for each teen and make changes that allow learning in ways that work best for them.

People with ADHD may also have other problems, such as depression, anxiety, or learning disabilities like dyslexia, that require treatment. They also may be at greater risk for smoking and using drugs, especially if the ADHD is not appropriately treated. That's why proper diagnosis and treatment are critical.

If You or Someone You Know Has ADHD
Most teens with ADHD are diagnosed as kids, but some people aren't diagnosed until they're in their teens or even older. It's normal to feel overwhelmed, scared, or even angry if you've been diagnosed with ADHD. That's one thing counseling can help with. Talking about those feelings and dealing with them often makes the process much easier.

If you have ADHD, you may not be aware that you're behaving in a way that's different from others; you're just doing what comes naturally. This can sometimes cause problems with people who don't understand or know about your condition. For example, you might speak your mind to someone only to get the feeling that you've shocked or offended that person. You may not understand why people get mad at you.

Learning all you can about your condition can be a huge help. The more you understand, the more involved you can be in your own treatment. Here are some of the things you might try to help with school and relationships:

Drugs : One Size Does Not Fit All -Lecture

2012-01-02T08:45:00.000+05:30

There are a number of causes for variation in drug response across the population, but differences in genetics are an important factor. Russ Altman, Professor & Chair of Bioengineering and Professor of Genetics and Medicine, discusses how variations in genetics can alter the "typical" response as well as touch upon the ethical issues with the use of this knowledge.Russ Altman for the Stanford University

Subscribe in a reader

Russ Altman started his education in Harvard university his work was primary in biochemistry and molecular biology,he came to Stanford and received his phd in Medical Information Science and MD in Stanford medical school

He was the president of International Society for Computational Biology (2000-2001) ,In Stanford he is professor of Genetics ,Bioengineering ,Medicine and computer science and He is the chairman of Bioengineering department.

In this lecture Dr.Russ Altman speaks about variation drug response,Human genome ,Pharmacology

This lecture will very useful for those who are interested in Drug designing,Bioinformatics students.

Endocrine System Animation

2012-01-02T08:43:00.001+05:30

The endocrine system is an integrated system of small organs that involve the release of extracellular signaling molecules known as hormones. The endocrine system is instrumental in regulating metabolism, growth, development and puberty, tissue function, and also plays a part in determining mood.The field of medicine that deals with disorders of endocrine glands is endocrinology, a branch of the wider field of internal medicine.

Function

Subscribe in a reader

The Endocrine system is an information signal system much like the nervous system. However, the nervous system uses nerves to conduct information, whereas the endocrine system mainly uses blood vessels as information channels. Glands located in many regions of the body release into the bloodstream specific chemical messengers called hormones. Hormones regulate the many and varied functions of an organism, e.g., mood, growth and development, tissue function, and metabolism, as well as sending messages and acting on them.

Genetic Code Lecture

2012-01-02T08:38:00.000+05:30

The genetic code is the set of rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins (amino acid sequences) by living cells. Specifically, the code defines a mapping between tri-nucleotide sequences called codons, and amino acids; every triplet of nucleotides in a nucleic acid sequence specifies a single amino acid. Because the vast majority of genes are encoded with exactly the same code (see #RNA codon table), this particular code is often referred to as the canonical or standard genetic code, or simply the genetic code, though in fact there are many variant codes; thus, the canonical genetic code is not universal. For example, in humans, protein synthesis in mitochondria relies on a genetic code that varies from the canonical code.

Subscribe in a reader

It is important to know that not all genetic information is stored as the genetic code. All organisms' DNA contain regulatory sequences, intergenic segments, chromosomal structural areas, which can contribute greatly to phenotype but operate using a distinct sets of rules which may or may not be as straightforward as the well-defined codon-to-amino acid paradigm which underlies the genetic code.

Cracking the genetic code

After the structure of DNA was deciphered by James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin, serious efforts to understand the nature of the encoding of proteins began. George Gamov postulated that a three-letter code must be employed to encode the 20 different amino acids used by living cells to encode proteins (because 3 is the smallest n such that 4n is at least 20). The fact that codons did consist of three DNA bases was first demonstrated in the Crick, Brenner et al. experiment.

The first elucidation of a codon was done by Marshall Nirenberg and Heinrich J. Matthaei in 1961 at the National Institutes of Health.They used a cell-free system to translate a poly-uracil RNA sequence (or UUUUU... in biochemical terms) and discovered that the polypeptide they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced from this poly-phenylalanine that the codon UUU specified the amino-acid phenylalanine.Extending this work, Nirenberg and his coworkers were able to determine the nucleotide makeup of each codon. In order to determine the order of the sequence, trinucleotides were bound to ribosomes and radioactively labeled aminoacyl-tRNA was used to determine which amino acid corresponded to the codon. Nirenberg's group was able to determine the sequences of 54 out of 64 codons. Subsequent work by Har Gobind Khorana identified the rest of the code, and shortly thereafter Robert W. Holley determined the structure of transfer RNA, the adapter molecule that facilitates translation. This work was based upon earlier studies by Severo Ochoa, who received the Nobel prize in 1959 for his work on the enzymology of RNA synthesis. In 1968, Khorana, Holley and Nirenberg also received the Nobel Prize in Physiology or Medicine for their work.

Nanotechnology Takes Off - KQED QUEST

2012-01-02T08:26:00.000+05:30

From Lawrence Berkeley National Labs to Silicon Valley, researchers are manipulating particles at the atomic level, ushering in potential cures for cancer, clothes that don't stain, and solar panels as thick as a sheet of paper.

Venus Fly trap

2012-01-02T08:24:00.000+05:30

Venus Flytrap, Dionaea muscipula, is a carnivorous plant that catches and digests animal prey (mostly insects and arachnids). The trapping structure is formed by the terminal portion of each of the plant's leaves. The plant's common name refers to Venus, the Roman goddess of love, whereas the genus name refers to Dione. Dionaea is a monotypic genus closely related to the waterwheel plant and sundews.

The Venus Flytrap is a small herb, forming a rosette of four to seven leaves, which arise from a short subterranean stem that is actually a bulb-like rhizome. Each leaf reaches a maximum size of about three to ten centimeters, depending on the time of year; longer leaves with robust traps are usually formed after flowering. Flytraps that have more than 7 leaves are colonies formed by rosettes that have divided beneath the ground.

The leaf blade is divided into two regions: a flat, heart shaped photosynthetic capable petiole, and a pair of terminal lobes hinged at the midrib, forming the trap which is the true leaf. The upper surface of these lobes contains red anthocyanin pigments and its edges secrete mucilage. The lobes exhibit rapid plant movements, snapping shut when stimulated by prey. The trapping mechanism is tripped when prey items stumble against one of the three hair-like trichomes that are found on the upper surface of each of the lobes. The trapping mechanism is so specialized that it can distinguish between living prey and non-prey stimuli such as falling raindrops; two trigger hairs must be touched in succession or one hair touched twice,whereupon the lobes of the trap will snap shut in about 0.1 seconds.The edges of the lobes are fringed by stiff hair-like protrusions or cilia, which mesh together and prevent large prey items from escaping. (These protrusions, and the trigger hairs, are probably homologous with the tentacles found in this plant’s close relatives, the sundews.) The holes in the meshwork allow small prey to escape, presumably because the benefit that would be obtained from them would be less than the cost of digesting them. If the prey is too small and escapes, the trap will reopen within 12 hours. If the prey moves around in the trap, it tightens and digestion begins more quickly.

Speed of closing can vary depending on the amount of humidity, light, size of prey, and general growing conditions. The speed with which traps close can be used as an indicator of a plant's general health. Venus Flytraps are not as humidity dependent as are some other carnivorous plants, such as Nepenthes, Cephalotus, most Heliamphora, and some Drosera.

The Venus Flytrap exhibits variations in petiole shape and length and whether the leaf lies flat on the ground or extends up at an angle of about 40-60 degrees. The four major forms are: 'typica', the most common, with broad decumbent petioles; 'erecta', with leaves at a 45 degree angle; 'linearis', with narrow petioles and leaves at 45 degrees; and 'filiformis', with extremely narrow or linear petioles. Except for 'filiformis', all of these can be stages in leaf production of any plant depending on season (decumbent in summer versus short versus semi-erect in spring), length of photoperiod (long petioles in spring versus short in summer), and intensity of light (wide petioles in low light intensity versus narrow in brighter light).

Mechanism of trapping

The Venus Flytrap is one of a very small group of plants that are capable of rapid movement, such as Mimosa, the Telegraph plant, sundews and bladderworts.

The mechanism by which the trap snaps shut involves a complex interaction between elasticity, turgor and growth. In the open, untripped state, the lobes are convex (bent outwards), but in the closed state, the lobes are concave (forming a cavity). It is the rapid flipping of this bistable state that closes the trap, but the mechanism by which this occurs is still poorly understood. When the trigger hairs are stimulated, an action potential (mostly involving calcium ions — see calcium in biology) is generated, which propagates across the lobes and stimulates cells in the lobes and in the midrib between them. Exactly what this stimulation does is still debated: cells in the outer layers of the lobes and midrib may rapidly secrete protons into their cell walls, loosening them and allowing them to swell rapidly by osmosis and acid growth; alternatively, cells in the inner layers of the lobes and midrib may rapidly secrete other ions, allowing water to follow by osmosis, and the cells to collapse. Both, either or neither of these mechanisms may play a role.

If the prey is unable to escape, it will continue to stimulate the inner surface of the lobes, and this causes a further growth response that forces the edges of the lobes together, eventually sealing the trap hermetically and forming a 'stomach' in which digestion occurs. Digestion is catalysed by enzymes secreted by glands in the lobes. Digestion takes about ten days, after which the prey is reduced to a husk of chitin. The trap then reopens, and is ready for reuse, even though the trap rarely catches more than three insects in its lifetime.

Habitat

The Venus Flytrap is found in nitrogen-poor environments, such as bogs and wet savannahs, and survives in wet sandy and peaty soils. Although it has been successfully transplanted and grown in many locales around the world, it is found natively only in North and South Carolina in the United States, specifically within a 100 mile radius of Wilmington, North Carolina.One such place is North Carolina's Green Swamp. There also appears to be a naturalized species of Venus Flytraps in northern Florida as well as populations in the New Jersey Pine Barrens. According to anecdotal evidence, a well-known horticulturist dropped thousands of seeds in Florida in hopes of spreading this plant. The nutritional poverty of the soil is the reason that the plant relies on such elaborate traps: insect prey provide the nitrogen for protein formation that the soil cannot. The Venus Flytrap is not a tropical plant and can tolerate mild winters. In fact, Venus Flytraps that do not go through a period of winter dormancy will weaken and die after a period of time.

DNA Polymerase and other factors

2012-01-02T08:22:00.003+05:30

DNA polymerase is an enzyme that assists in DNA replication. Such enzymes catalyze the polymerization of deoxyribonucleotides alongside a DNA strand, which they "read" and use as a template. The newly-polymerized molecule is complementary to the template strand and identical to the template's partner strand.

DNA polymerase is considered to be a holoenzyme since it requires a magnesium ion as a co-factor to function properly. In the absence of the magnesium ion, it is referred to as an apoenzyme.

DNA-Polymerase initiates DNA replication by binding to a piece of single-stranded DNA.

Function

DNA polymerase can add free nucleotides to only the 3’ end of the newly-forming strand. This results in elongation of the new strand in a 5'-3' direction. No known DNA polymerase is able to begin a new chain (de novo). DNA polymerase can add a nucleotide onto only a preexisting 3'-OH group, and, therefore, needs a primer at which it can add the first nucleotide. Primers consist of RNA and DNA bases with the first two bases always being RNA, and are synthesized by another enzyme called primase. An enzyme known as a helicase is required to unwind DNA from a double-strand structure to a single-strand structure to facilitate replication of each strand consistent with the semiconservative model of DNA replication.

Error correction is a property of some, but not all, DNA polymerases. This process corrects mistakes in newly-synthesized DNA. When an incorrect base pair is recognized, DNA polymerase reverses its direction by one base pair of DNA. The 3'->5' exonuclease activity of the enzyme allows the incorrect base pair to be excised (this activity is known as proofreading). Following base excision, the polymerase can re-insert the correct base and replication can continue.

Variation across species

DNA polymerases have highly-conserved structure, which means that their overall catalytic subunits vary, on a whole, very little from species to species. Conserved structures usually indicate important, irreplicable functions of the cell, the maintenance of which provides evolutionary advantages.

Some viruses also encode special DNA polymerases that may selectively replicate viral DNA through a variety of mechanisms. Retroviruses encode an unusual DNA polymerase called reverse transcriptase, which is an RNA-dependent DNA polymerase (RdDp). It polymerizes DNA from a template of RNA.

DNA polymerase families

Based on sequence homology, DNA polymerases can be further subdivided into seven different families: A, B, C, D, X, Y, and RT.

Family A

Family A polymerases contain both replicative and repair polymerases. Replicative members from this family include the extensively-studied T7 DNA polymerase, as well as the eukaryotic mitochondrial DNA Polymerase γ. Among the repair polymerases are E. coli DNA pol I, Thermus aquaticus pol I, and Bacillus stearothermophilus pol I. These repair polymerases are involved in excision repair and processing of Okazaki fragments generated during lagging strand synthesis.

Family B

Family B polymerases mostly contain replicative polymerases and include the major eukaryotic DNA polymerases α, δ, ε, (see Greek letters used in mathematics) and also DNA polymerase ζ. Family B also includes DNA polymerases encoded by some bacteria and bacteriophages, of which the best-characterized are from T4, Phi29, and RB69 bacteriophages. These enzymes are involved in both leading and lagging strand synthesis. A hallmark of the B family of polymerases is remarkable accuracy during replication; and many have strong 3'-5' exonuclease activity (except DNA polymerase α and ζ, which have no proofreading activity).

Family C

Family C polymerases are the primary bacterial chromosomal replicative enzymes. DNA Polymerase III alpha subunit from E. coli possesses no known nuclease activity. A separate subunit, the epsilon subunit, possesses the 3'-5' exonuclease activity used for editing during chromosomal replication.

Family D

Family D polymerases are still not very well characterized. All known examples are found in the Euryarchaeota subdomain of Archaea and are thought to be replicative polymerases.

Families X

Family X contains the well-known eukaryotic polymerase pol β, as well as other eukaryotic polymerases such as pol σ, pol λ, pol μ, and terminal deoxynucleotidyl transferase (TdT). Pol β is required for short-patch base excision repair, a DNA repair pathway that is essential for repairing abasic sites. Pol λ and Pol μ are involved in non-homologous end-joining, a mechanism for rejoining DNA double-strand breaks. TdT is expressed only in lymphoid tissue, and adds "n nucleotides" to double-strand breaks formed during V(D)J recombination to promote immunological diversity. The yeast Saccharomyces cerevisiae has only one Pol X polymerase, Pol4, which is involved in non-homologous end-joining.

Families Y

The Y-family polymerases differ from others in having a low fidelity on undamaged templates and in their ability to replicate through damaged DNA. Members of this family are hence called translesion synthesis (TLS) polymerases. Depending on the lesion, TLS polymerases can bypass the damage in an error-free or error-prone fashion, the latter resulting in elevated mutagenesis. Xeroderma pigmentosum variant (XPV) patients for instance have mutations in the gene encoding Pol η (eta), which is error-free for UV-lesions. In XPV patients, alternative error-prone polymerases, e.g., Polζ (zeta) (polymerase ζ is a B Family polymerase), are thought to be involved in mistakes that result in the cancer predisposition of these patients. Other members in humans are Pol ι (iota), Pol κ (kappa), and Rev1 (terminal deoxycytidyl transferase). In E.coli, two TLS polymerases, Pol IV (DINB) and PolV (UmuD'2C), are known.

Family RT

The reverse transcriptase family contains examples from both retroviruses and eukaryotic polymerases. The eukaryotic polymerases are usually restricted to telomerases. These polymerases use an RNA template to synthesize the DNA strand.

Prokaryotic DNA polymerases Bacteria have 5 known DNA polymerases:

Pol I: implicated in DNA repair; has both 5'->3'(Polymerase) activity and 3'->5' (Proofreading) exonuclease activity.
Pol II: involved in replication of damaged DNA; has 3'->5' exonuclease activity.
Pol III: the main polymerase in bacteria (elongates in DNA replication); has 3'->5' exonuclease proofreading ability.
Pol IV: a Y-family DNA polymerase.
Pol V: a Y-family DNA polymerase; participates in bypassing DNA damage.

Eukaryotic DNA polymerases Eukaryotes have at least 15 DNA Polymerases:

Pol α (synonyms are DNA primase, RNA polymerase): acts as a primase (synthesizing an RNA primer), and then as a DNA Pol elongating that primer with DNA nucleotides. After around 20 nucleotides elongation is taken over by Pol δ (on the lagging strand) and ε (on the leading strand).
Pol β: Implicated in repairing DNA, in base excision repair and gap-filling synthesis.
Pol γ: Replicates mitochondrial DNA.
Pol δ: Highly processive and has proofreading 3'->5' exonuclease activity. Thought to be the main polymerase involved in lagging strand synthesis, though there is still debate about its role.
Pol ε: Also highly processive and has proofreading 3'->5' exonuclease activity. Highly related to pol δ, and thought to be the main polymerase involved in leading strand synthesis, though there is again still debate about its role.
η, ι, κ, and Rev1 are Y-family DNA polymerases and Pol ζ is a B-family DNA polymerase. These polymerases are involved in the bypass of DNA damage.
There are also other eukaryotic polymerases known, which are not as well characterized: θ, λ, φ, σ, and μ. There are also others, but the nomenclature has become quite jumbled.

None of the eukariotic polymerases can remove primers (5'->3' exonuclease activity); that function is carried out by other enzymes. Only the polymerases that deal with the elongation (γ, δ and ε) have proofreading ability (3'->5' exonuclease). nuclease is a great advocate for DNA replication.

Lymphatic System Animation

2012-01-02T08:21:00.000+05:30

The lymphatic system in vertebrates is a network of conduits that carry a clear fluid called lymph. It also includes the lymphoid tissue that the lymph travels through. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated with the digestive system such as the tonsils. The system also includes all the structures dedicated to the circulation and production of lymphocytes, which includes the spleen, thymus, bone marrow and the lymphoid tissue associated with the digestive system. The lymphatic system as we know it today, was first described independently by Rudbeck and Bartholin.

The dissolved constituents of the blood do not directly come in contact with the cells and tissues in the body, but first enter the interstitial fluid, and then the cells of the body. Lymph is the fluid that is formed when interstitial fluid enters the conduits of the lymphatic system. The lymph is not pumped through the body like blood, it is moved mostly by the contractions of skeletal muscles.

The lymphatic system has three interrelated functions. It is responsible for the removal of interstitial fluid from tissues. It absorbs and transports fatty acids and fats as chyle to the circulatory system. The last function of the lymphatic system is the production of immune cells, such as lymphocytes, including antibody producing plasma cells and monocytes.

The study of lymphatic drainage of various organs is important in treatment and diagnosis of cancer. The lymphatic system, because of its physical proximity to many tissues of the body, is responsible for carrying cancerous cells between the various parts of the body in a process called metastasis. The intervening lymph nodes can trap the cancer cells. If they are not successful in destroying the cancer cells the nodes may become sites of secondary tumors.

Diseases and other problems of the lymphatic system can cause swelling and other symptoms. Problems with the system can impair the body's ability to fight infections.

Organization

The lymphatic system can be broadly divided into the conducting system and the lymphoid tissue.

The conducting system carries the lymph and consists of tubular vessels that include the lymph capillaries, the lymph vessels and the right and the thoracic ducts.

The lymphoid tissue is primarily involved in immune responses, and consists of lymphocytes and other white blood cells enmeshed in connective tissue through which the lymph passes. Regions of the lymphoid tissue that are densely packed with lymphocytes are known as lymphoid follicles. Lymphoid tissue can either be structurally well organized as lymph nodes or may consist of loosely organized lymphoid follicles known as the mucosa-associated lymphoid tissue.

Formation of lymph

Blood supplies nutrients, and important metabolites to the tissues, and collects back the waste products that they produce, which requires exchange of respective constituents between the blood and tissues. However, this exchange is not direct, and is effected through an intermediary called interstitial fluid or tissue fluid that the blood forms. Interstitial fluid (ISF) is the fluid that occupies the spaces between the cells and acts as their immediate environment. The composition of ISF keeps on changing depending upon what substances are removed or added by blood and the cells in the vicinity. Water and solutes can freely pass (diffuse) between the ISF and blood, and thus both are in dynamic equilibrium with each other; exchange between the two fluids occurs across the walls of small blood vessels called capillaries.

ISF forms at the arterial (coming from the heart) end of the capillaries because of higher pressure of blood, and most of it returns to its venous ends and venules; the rest (10—20%) enters the lymph capillaries as lymph. Thus, lymph when formed is a watery clear liquid with the same composition as the ISF. However, as it flows through the lymph nodes it comes in contact with blood, and tends to accumulate more cells (particularly, lymphocytes) and proteins.

Lymphatic circulation

Tubular vessels transport back lymph to the blood ultimately replacing the volume lost from the blood during the formation of the interstitial fluid. These channels are the lymphatic channels or simply called lymphatics.

General structure of Lymphatics

The general structure of lymphatics is based on that of blood vessels. There is an inner lining of single flattened cells composed of a type of epithelium that is called endothelium, and the cells are called endothelial cells. This layer functions to mechanically transport fluid and since the basement membrane on which it rests is discontinuous, it is quite leaky. The next layer is that of smooth muscles that are arranged in a circular fashion around the endothelium, which by shortening (contracting) or relaxing alter the diameter (caliber) or the lumen. The outermost layer is the adventitia that consists of fibrous tissue. The general structure described here is seen only in larger lymphatics; smaller lymphatics have fewer layers. The smallest vessels (lymphatic or lymph capillaries) lack both the muscular layer and the outer adventitia. As they proceed forward and in their course are joined by other capillaries, they grow larger and first take on an adventitia, and then smooth muscles.

The whole lymphatic conducting system broadly consists of two types of channels—the initial lymphatics, the prelymphatics or lymph capillaries that specialize in collection of the lymph from the ISF, and the larger lymph vessels that propel the lymph forward.

Unlike the cardiovascular system, the lymphatic system is not closed and has no central pump. Lymph movement occurs despite low pressure due to peristalsis (propulsion of the lymph due to alternate contraction and relaxation of smooth muscle), valves, and compression during contraction of adjacent skeletal muscle and arterial pulsation.

Lymph capillaries

The lymphatic circulation begins with blind ending (closed at one end) highly permeable superficial lymph capillaries, formed by endothelial cells with button-like junctions between them that allow fluid to pass through them when the interstitial pressure is sufficiently high. These button-like junctions consist of protein filaments like platelet endothelial cell adhesion molecule-1 or (PECAM-1). A valve system in place here does not allow the absorbed lymph to leak back into the ISF. There is another system of semilunar (semi=half; lunar=related to the Moon) valves that does not allow back-flow of lymph along the lumen of the vessel. Lymph capillaries have many interconnections (anastomosis) between them, and form a very fine network.

Rhythmic contraction of the vessel walls through movements may also help draw fluid into the smallest lymphatic vessels, capillaries. If tissue fluid builds up the tissue will swell; this is called edema. As the circular path through the body's system continues, the fluid is then transported to progressively larger lymphatic vessels culminating in the right lymphatic duct (for lymph from the right upper body) and the thoracic duct (for the rest of the body); both ducts drain into the circulatory system at the right and left subclavian veins. The system collaborates with white blood cells in lymph nodes to protect the body from being infected by cancer cells, fungi, viruses or bacteria. This is known as a secondary circulatory system.

Lymph vessels

The lymph capillaries drain the lymph to larger contractile lymphatics, which have valves as well as smooth muscle walls. These are called the collecting lymphatics. As the collecting lymph vessel accumulates lymph from more and more lymph capillaries in its course, it become larger and is called the afferent lymph vessel as it enters a lymph node. Here the lymph percolates through the lymph node tissue and is removed by the efferent lymph vessel. An efferent lymph vessel my directly drain into one of the (right or thoracic) lymph ducts, or may empty another lymph node as its afferent lymph vessel. Both the lymph ducts return the lymph to the blood stream by emptying into the subclavian veins

The functional unit of a lymph vessel is known as a lymphangion that is the segment between two valves. Since, it is contractile, depending upon ratio of its length:radius, it can act like a contractile chamber propelling the fluid ahead, or as a resistance vessel tending to stop the lymph in its place.

Transposons

2012-01-02T08:19:00.000+05:30

Transposons are sequences of DNA that can move around to different positions within the genome of a single cell, a process called transposition. In the process, they can cause mutations and change the amount of DNA in the genome. Transposons were also once called "jumping genes", and are examples of mobile genetic elements. Discovered by Barbara McClintock early in her career, the discovery earned her a Nobel prize in 1983. There are a variety of mobile genetic elements, and they can be grouped based on their mechanism of transposition. Class I mobile genetic elements, or retrotransposons, move in the genome by being transcribed to RNA and then back to DNA by reverse transcriptase, while class II mobile genetic elements move directly from one position to another within the genome using a transposase to "cut and paste" them within the genome. Transposons are very useful to researchers as a means to alter DNA inside of a living organism. Transposons make up a large fraction of genome sizes which is evident through the C-values of eukaryotic species.

Types of transpositions

Transposons are classified into two classes based on their mechanism of transposition. 10% of the human genome is made up of transposons.

Class I: Retrotranspositions

Retrotransposons work by copying themselves and pasting copies back into the genome in multiple places. Initially retrotransposons copy themselves to RNA (transcription) but, in addition to being transcribed, the RNA is copied into DNA by a reverse transcriptase (often coded by the transposon itself) and inserted back into the genome.

Retrotransposons behave very similarly to retroviruses, such as HIV, giving a clue to the evolutionary origins of such viruses.

There are three main classes of retrotransposons:

Viral: encode reverse transcriptase (to reverse transcribe RNA into DNA), have long terminal repeats (LTRs), similar to retroviruses
LINEs: encode reverse transcriptase, lack LTRs, transcribed by RNA polymerase II
Nonviral superfamily: do not code for reverse transcriptase, transcribed by RNA polymerase III

Retroviruses as transposable elements

Retroviruses were first identified 80 years ago as agents involved in the onset of cancer. More recently the AIDS epidemic has been shown to be due to the HIV retrovirus. In the early 1970s it was discovered that retroviruses had the ability to replicate their RNA genomes via conversion into DNA which became stably integrated in the DNA of the host cell. It is only comparatively recently that retroviruses have been recognized as particularly specialized forms of eukaryotic transposons. In effect they are transposons which move via RNA intermediates that usually can leave the host cells and infect other cells. The integrated DNA form (provirus) of the retrovirus bears a marked similarity to a transposon.

Class II: DNA transposons

The major difference of class II transposons from retrotransposons is that their transposition mechanism does not involve an RNA intermediate. Class II transposons usually move by a mechanism analogous to cut and paste, rather than copy and paste, using the transposase enzyme. Different types of transposase work in different ways. Some can bind to any part of the DNA molecule, and the target site can therefore be anywhere, while others bind to specific sequences. Transposase makes a staggered cut at the target site producing sticky ends, cuts out the transposon and ligates it into the target site. A DNA polymerase fills in the resulting gaps from the sticky ends and DNA ligase closes the sugar-phosphate backbone. This results in target site duplication and the insertion sites of DNA transposons may be identified by short direct repeats (a staggered cut in the target DNA filled by DNA polymerase) followed by inverted repeats (which are important for the transposon excision by transposase).

Not all DNA transposons transpose through cut and paste mechanism. In some cases a replicative transposition is observed in which transposon replicates itself to a new target site.

The transposons which only move by cut and paste may duplicate themselves if the transposition happens during S phase of the cell cycle when the "donor" site has already been replicated, but the "target" site has not.

Both classes of transposon may lose their ability to synthesise reverse transcriptase or transposase through mutation, yet continue to jump through the genome because other transposons are still producing the necessary enzyme.

The transposition cycle of retroviruses has other similarities to prokaryotic transposons, which suggest a distant familial relationship between these two types of transposon. Crucial intermediates in retrovirus transposition are extrachromosomal DNA molecules. These are generated by copying the RNA of the virus particle into DNA by a retrovirus-encoded polymerase called reverse transcriptase. The extra chromosomal linear DNA is the direct precursor of the integrated element and the insertion mechanism bears a strong similarity to "cut and paste" transposition.

Examples

The first transposons were discovered in maize (Zea mays), (corn species) by Barbara McClintock in 1948, for which she was awarded a Nobel Prize in 1983. She noticed insertions, deletions, and translocations, caused by these transposons. These changes in the genome could, for example, lead to a change in the color of corn kernels. About 50% of the total genome of maize consists of transposons. The Ac/Ds system McClintock described are class II transposons.
One family of transposons in the fruit fly Drosophila melanogaster are called P elements. They seem to have first appeared in the species only in the middle of the twentieth century. Within 50 years, they have spread through every population of the species. Gerald Rubin and Allan Spradling pioneered technology to use artificial P elements to insert genes into Drosophila by injecting the embryo.
Transposons in bacteria usually carry an additional gene for function other than transposition---often for antibiotic resistance. In bacteria, transposons can jump from chromosomal DNA to plasmid DNA and back, allowing for the transfer and permanent addition of genes such as those encoding antibiotic resistance (multi-antibiotic resistant bacterial strains can be generated in this way). Bacterial transposons of this type belong to the Tn family. When the transposable elements lack additional genes, they are known as insertion sequences.
The most common form of transposon in humans is the Alu sequence. The Alu sequence is approximately 300 bases long and can be found between 300,000 and a million times in the human genome.
Mu phage transposition is the best known example of replicative transposition. Its transposition mechanism is somewhat similar to a homologous recombination.

Transposons causing diseases

Transposons are mutagens. They can damage the genome of their host cell in different ways:

A transposon or a retroposon that inserts itself into a functional gene will most likely disable that gene.
After a transposon leaves a gene, the resulting gap will probably not be repaired correctly.
Multiple copies of the same sequence, such as Alu sequences can hinder precise chromosomal pairing during mitosis and meiosis, resulting in unequal crossovers, one of the main reasons for chromosome duplication.

Diseases that are often caused by transposons include hemophilia A and B, severe combined immunodeficiency, porphyria, predisposition to cancer, and Duchenne muscular dystrophy.

Additionally, many transposons contain promoters which drive transcription of their own transposase. These promoters can cause aberrant expression of linked genes, causing disease or mutant phenotypes. Evolution of transposons

The evolution of transposons and their effect on genome evolution is currently a dynamic field of study.

Transposons are found in all major branches of life. They may or may not have originated in the last universal common ancestor, or arisen independently multiple times, or perhaps arisen once and then spread to other kingdoms by horizontal gene transfer. While transposons may confer some benefits on their hosts, they are generally considered to be selfish DNA parasites that live within the genome of cellular organisms. In this way, they are similar to viruses. Viruses and transposons also share features in their genome structure and biochemical abilities, leading to speculation that they share a common ancestor.

Since excessive transposon activity can destroy a genome, many organisms seem to have developed mechanisms to reduce transposition to a manageable level. Bacteria may undergo high rates of gene deletion as part of a mechanism to remove transposons and viruses from their genomes while eukaryotic organisms may have developed the RNA interference (RNAi) mechanism as a way of reducing transposon activity. In the nematode Caenorhabditis elegans, some genes required for RNAi also reduce transposon activity.

Transposons may have been co-opted by the vertebrate immune system as a means of producing antibody diversity. The V(D)J recombination system operates by a mechanism similar to that of transposons.

Evidence exists that transposable elements may act as mutators in bacteria.

Applications

Transposons were first discovered in the plant maize (Zea mays, corn species), which is named dissociator (Ds). Likewise, the first transposon to be molecularly isolated was from a plant (Snapdragon). Appropriately, transposons have been an especially useful tool in plant molecular biology. Researchers use transposons as a means of mutagenesis. In this context, a transposon jumps into a gene and produces a mutation. The presence of the transposon provides a straightforward means of identifying the mutant allele, relative to chemical mutagenesis methods.

Sometimes the insertion of a transposon into a gene can disrupt that gene's function in a reversible manner; transposase mediated excision of the transposon restores gene function. This produces plants in which neighboring cells have different genotypes. This feature allows researchers to distinguish between genes that must be present inside of a cell in order to function (cell-autonomous) and genes that produce observable effects in cells other than those where the gene is expressed.

Egg fertilization

2012-01-02T08:17:00.000+05:30

Fertilization (also known as conception, fecundation and syngamy), is fusion of gametes to produce a new organism of the same species. In animals, the process involves a sperm fusing with an ovum, which eventually leads to the development of an embryo. Depending on the animal species, the process can occur within the body of the female in internal fertilization, or outside in the case of external fertilization.

The entire process of development of new individuals is called procreation, the act of species reproduction.

Subscribe in a reader

The term conception commonly refers to fertilization, but is sometimes defined as implantation or even "the point at which human life begins", and is thus a subject of semantic arguments about the beginning of pregnancy, within the abortion debate. Gastrulation is the point in development when the implanted blastocyst develops three germ layers, the endoderm, the exoderm and the mesoderm. It is at this point that the genetic code of the father becomes fully involved in the development of the embryo. Until this point in development, twinning is possible. Additionally, interspecies hybrids survive only until gastrulation, and have no chance of development afterward. However this stance is not entirely warranted since human developmental biology literature refers to the "conceptus" and the medical literature refers to the "products of conception" as the post-implantation embryo and its surrounding membranes. The term "conception" is not usually used in scientific literature because of its variable definition and connotation.

Vitaxin

2012-01-01T07:37:00.003+05:30

Vitaxin is a humanized monoclonal antibody against the vascular integrin avb3[1]. It is shown to be a promising angiogenesis inhibitor used in the treatment of some forms of cancer. At this time Vitaxin is in Phase II trial which is where the dose has already been proven safe in Phase I, and has been ramped up to test therapeutic levels in human participants. It is currently in clinical trials as a treatment for colorectal cancer.

Gastroesophageal reflux disease(GERD)

2011-12-31T08:10:00.000+05:30

Gastroesophageal reflux disease (American English and Canadian English) or Gastro-oesophageal reflux disease (British English, Hiberno-English, Australian English, New Zealand English, South African English) and abbreviated to either GERD or GORD is defined as chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus.

This is commonly due to transient or permanent changes in the barrier between the esophagus and the stomach. This can be due to incompetence of the cardia, transient cardia relaxation, impaired expulsion of gastric reflux from the esophagus, or a hiatus hernia.

Subscribe in a reader

Symptoms
Adults

Heartburn is the major symptom of acid in the esophagus, characterized by burning discomfort behind the breastbone (sternum). Findings in GERD include esophagitis (reflux esophagitis) — inflammatory changes in the esophageal lining (mucosa) —, strictures, difficulty swallowing (dysphagia), and chronic chest pain. Patients may have only one of those symptoms. Typical GERD symptoms include cough, hoarseness, voice changes, chronic ear ache, burning chest pains, nausea or sinusitis. GERD complications include stricture formation, Barrett's esophagus, esophageal spasms, esophageal ulcers, and possibly even lead to esophageal cancer, especially in adults over 60 years old.

Occasional heartburn is common but does not necessarily mean one has GERD. Patients with heartburn symptoms more than once a week are at risk of developing GERD. A hiatal hernia is usually asymptomatic, but the presence of a hiatal hernia is a risk factor for developing GERD.

Children

GERD may be difficult to detect in infants and children. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems. Inconsolable crying, failure to gain adequate weight, refusing food, bad breath, and belching or burping are also common. Children may have one symptom or many — no single symptom is universal in all children with GERD.

It is estimated that of the approximately 4 million babies born in the U.S. each year, up to 35% of them may have difficulties with reflux in the first few months of their life. Most of those children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition.

Babies' immature digestive systems are usually the cause, and most infants stop having acid reflux by the time they reach their first birthday. Some children do not outgrow acid reflux, however, and continue to have it into their teen years. Children who have had heartburn that does not seem to go away, or any other GERD symptoms for a while, should talk to their parents and visit their doctor.

Diagnosis

A detailed history taking is vital to the diagnosis. Useful investigations may include barium swallow X-rays, esophageal manometry, 24-hour esophageal pH monitoring and Esophagogastroduodenoscopy (EGD). In general, an EGD is done when the patient does not respond well to treatment, or has alarm symptoms including: dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate once-in-a-lifetime endoscopy for patients with longstanding GERD, to evaluate the possible presence of Barrett's esophagus, a precursor lesion for esophageal adenocarcinoma.

Esophagogastroduodenoscopy (EGD) (a form of endoscopy) involves insertion of a thin scope through the mouth and throat into the esophagus and stomach (often while the patient is sedated) in order to assess the internal surfaces of the esophagus, stomach, and duodenum.

Biopsies can be performed during gastroscopy and these may show:

Edema and basal hyperplasia (non-specific inflammatory changes)
Lymphocytic inflammation (non-specific)
Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
Eosinophilic inflammation (usually due to reflux)
Goblet cell intestinal metaplasia or Barretts esophagus.
Elongation of the papillae
Thinning of the squamous cell layer
Dysplasia or pre-cancer.
Carcinoma.

Reflux changes may be non-erosive in nature, leading to the entity non-erosive reflux disease.

What is Gout

2011-12-31T07:48:00.001+05:30

Gout is caused by buildup of uric acid,Uric acid crystalls travel and accumulate in the joints,in specially in feet and legs causing pain in the legs,crystals of monosodium urate or uric acid are deposited on the articular cartilage of joints, tendons and surrounding tissues. These crystals cause inflammation and pain, both severe. If unchecked, the crystals form tophi, which can cause significant tissue damage. Gout results from a combination of elevated concentrations of uric acid and overall acidity in the bloodstream. In isolation, neither elevated uric acid (hyperuricemia) nor acidity is normally sufficient to cause gout.

Subscribe in a reader Signs and symptoms

Gout is characterized by excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected joint. This occurs commonly in men in their toes but can appear in other parts of the body and affects women as well. Low-grade fever may also be present. The patient usually suffers from two sources of pain. The crystals inside the joint cause intense pain whenever the affected area is moved. The inflammation of the tissues around the joint also causes the skin to be swollen, tender and sore if it is even slightly touched. For example, a blanket or even the lightest sheet draping over the affected area could cause extreme pain.

Gout usually attacks the big toe (approximately 75 percent of first attacks); however, it also can affect other joints such as the ankle, heel, instep, knee, wrist, elbow, fingers, and spine. In some cases, the condition may appear in the joints of small toes that have become immobile due to impact injury earlier in life, causing poor blood circulation that leads to gout.

Hernia Repair animation

2011-12-31T07:39:00.001+05:30

It is generally advisable to repair hernias in a timely fashion, in order to prevent complications such as organ dysfunction, gangrene, and multiple organ dysfunction syndrome. Most abdominal hernias can be surgically repaired, and recovery rarely requires long-term changes in lifestyle. Uncomplicated hernias are principally repaired by pushing back, or "reducing", the herniated tissue, and then mending the weakness in muscle tissue (an operation called herniorrhaphy). If complications have occurred, the surgeon will check the viability of the herniated organ, and resect it if necessary. Modern muscle reinforcement techniques involve synthetic materials (a mesh prosthesis) that avoid over-stretching of already weakened tissue (as in older, but still useful methods). The mesh is placed over the defect, and sometimes staples are used to keep the mesh in place. Evidence suggests that this method has the lowest percentage of recurrences and the fastest recovery period. Increasingly, some repairs are performed through laparoscopes.

Subscribe in a reader

Many patients are managed through day surgery centers, and are able to return to work within a week or two, while heavy activities are prohibited for a longer period. Patients who have their hernias repaired with mesh often recover in a number of days. Surgical complications have been estimated to be up to 10%, but most of them can be easily addressed. They include surgical site infections, nerve and blood vessel injuries, injury to nearby organs, and hernia recurrence.

Generally, the use of external devices to maintain reduction of the hernia without repairing the underlying defect (such as hernia trusses, trunks, belts, etc.), is not advised. Exceptions are uncomplicated incisional hernias that arise shortly after the operation (should only be operated after a few months), or inoperable patients.

It is essential that the hernia not be further irritated by carrying out strenuous labour.

What is Cell Cycle Proteins

2011-12-29T10:44:00.002+05:30

Sequential activation of members of the cyclin-dependent protein kinase (CDK) family promotes the correct timing and ordering of events required for cell growth and cell division . In addition to driving progress through the cell cycle, CDKs are also the downstream targets of checkpoint pathways. These checkpoints act to ensure that critical cell cycle events have been successfully completed before the cell progresses into the next cell cycle stage. They are composed of a surveillance system that detects when a particular cell cycle event has not been correctly executed and a signal transduction pathway whose ultimate target can be a CDK.
Monomeric CDKs are inactive and require both association with a positive regulatory subunit, called a cyclin, and phosphorylation on a conserved threonine residue that lies within the activation loop for full activity. Both the CDK and cyclin families have multiple members, but only CDKs 1, 2, 4 and 6, when bound to their cognate cyclins, appear to have major roles in controlling cell cycle progression. These CDK/cyclin complexes are then additionally controlled by mechanisms that include inhibitory phosphorylation, protein association, subcellular localisation and targeted destruction of regulatory proteins.

Major Histocompatibility Complex

2011-12-28T08:19:00.001+05:30

Necrosis VS Apoptosis

2011-12-28T08:16:00.001+05:30

Extrinsic and Intrinsic pathway for Apoptosis

2011-12-28T08:11:00.002+05:30

Overview of the Extrinsic and Intrinsic pathway for Apoptosis

AVM Embolization

2011-12-16T09:03:00.000+05:30

Arteriovenous malformations are abnormal clusters of blood vessels which can be seen in any part of the human body. They are congenital in nature. In he brain ,AVM's may have no symptoms at all and the abnormality may be picked during a brain scan for another reason. However, one the commonest presentations is with a bleed in the brain resulting in paralysis or unconsciousness . Another form of presentation can be seizures . Its also known that AVM,s can at time's result in frequent head aches termed "vascular headaches". When detected, AVMs are ideally treated to prevent bleeding in future.

Gleevec

2011-12-16T09:01:00.001+05:30

Oxyhemoglobin dissociation curve

2011-12-16T08:55:00.000+05:30

The oxygen–haemoglobin dissociation curve (or oxygen–hemoglobin dissociation curve) plots the proportion of haemoglobin in its saturated form on the vertical axis against the prevailing oxygen tension on the horizontal axis. The oxyhaemoglobin dissociation curve is an important tool for understanding how our blood carries and releases oxygen. Specifically, the oxyhaemoglobin dissociation curve relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2), and is determined by what is called "haemoglobin's affinity for oxygen"; that is, how readily haemoglobin acquires and releases oxygen molecules into the fluid that surrounds it.

Bilirubin Metabolism

2011-12-16T08:48:00.000+05:30

Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal heme catabolism. Heme is formed from hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile, and its levels are elevated in certain diseases. It is responsible for the yellow color of bruises and the yellow discoloration in jaundice.

Function:

Bilirubin is created by the activity of biliverdin reductase on biliverdin. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin, has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.

Metabolism

Erythrocytes (red blood cells) generated in the bone marrow are disposed of in the spleen when they get old or damaged. This releases hemoglobin, which is broken down to heme, as the globin parts are turned into amino acids. The heme is then turned into unconjugated bilirubin in the macrophages of the spleen. This unconjugated bilirubin is not soluble in water. It is then bound to albumin and sent to the liver.

In the liver it is conjugated with glucuronic acid, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to urobilinogen, which is further metabolized to stercobilinogen, and finally oxidised to stercobilin. This stercobilin gives feces its brown color. Some of the urobilinogen is reabsorbed and excreted in the urine along with an oxidized form, urobilin.

Normally, a tiny amount of bilirubin is excreted in the urine, accounting for the light yellow color. If the liver’s function is impaired or when biliary drainage is blocked, some of the conjugated bilirubin leaks out of the hepatocytes and appears in the urine, turning it dark amber. The presence of this conjugated bilirubin in the urine can be clinically analyzed, and is reported as an increase in urine bilirubin. However, in disorders involving hemolytic anemia, an increased number of red blood cells are broken down, causing an increase in the amount of unconjugated bilirubin in the blood. As stated above, the unconjugated bilirubin is not water soluble, and thus one will not see an increase in bilirubin in the urine. Because there is no problem with the liver or bile systems, this excess unconjugated bilirubin will go through all of the normal processing mechanisms that occur (e.g., conjugation, excretion in bile, metabolism to urobilinogen, reabsorption) and will show up as an increase in urine urobilinogen. This difference between increased urine bilirubin and increased urine urobilinogen helps to distinguish between various disorders in those systems.

TCOYD Diabetes-Pregnancy II

2011-12-16T08:42:00.000+05:30

Steven Edelman, MD and perinatal specialist Thomas Moore, MD, discuss gestational diabetes including the causes, therapies, and recommendations for keeping mother and baby healthy throughout the pregnancy and delivery.

Mechanism of Capsaicin Pain Relief

2011-12-16T08:33:00.001+05:30

The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (VR1). First cloned in 1997, VR1 is an ion channel-type receptor. VR1, which can also be stimulated with heat and physical abrasion, permits cations to pass through the cell membrane and into the cell when activated. The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.

The VR1 ion channel has subsequently been shown to be a member of the superfamily of TRP ion channels, and as such is now referred to as TRPV1. There are a number of different TRP ion channels that have been shown to be sensitive to different ranges of temperature and probably are responsible for our range of temperature sensation. Thus, capsaicin does not actually cause a chemical burn, or indeed any direct tissue damage at all, when chili peppers are the source of exposure. The inflammation resulting from exposure to Capsaicin is believed to be the result of the body's reaction to nerve excitement. For example, the mode of action of capsaicin in inducing bronchoconstriction is thought to involve stimulation of C fibres culminating in the release of neuropeptides. Basically, the body inflames tissues as if it has undergone a burn or abrasion and the resulting inflammation can cause tissue damage in cases of extreme exposure, as is the case for many substances that trick the body into inflaming itself.