A bacterium undergoing sporulation will first replicate its DNA ,The replicated DNA as well as a small amount of cytoplasm is segregated at one end of the cell,The plasmid membrane of the bacterium then grows inwards to eventually separate replicated DNA and the surrounding cytoplasm from the rest of the cells. water diffuses from this small segregated portion into the surrounding cell and then new endospore develops a thick protein coat once the formation of the endospore is complete the original cell wall dissolves and parent cell dies. the endospore is released from the dead parent cell
Probiotics are dietary supplements and live microorganisms containing potentially beneficial bacteria or yeasts. According to the currently adopted definition by FAO/WHO, probiotics are: ‘Live microorganisms which when administered in adequate amounts confer a health benefit on the host’.
Lactic acid bacteria (LAB) are the most common type of microbes used. LAB have been used in the food industry for many years, because they are able to convert sugars (including lactose) and other carbohydrates into lactic acid. This not only provides the characteristic sour taste of fermented dairy foods such as yogurt, but also by lowering the pH may create fewer opportunities for spoilage organisms to grow, hence creating possible health benefits on preventing gastrointestinal infections.Strains of the genera Lactobacillus and Bifidobacterium, are the most widely used probiotic bacteria.
Probiotic bacterial cultures are intended to assist the body's naturally occurring gut flora, an ecology of microbes, to re-establish themselves. They are sometimes recommended by doctors, and, more frequently, by nutritionists, after a course of antibiotics, or as part of the treatment for gut related candidiasis. In these cases, the bacteria that work well with our bodies (see symbiosis) may decrease in number, an event which allows harmful competitors to thrive, to the detriment of our health. Claims are made that probiotics strengthen the immune system to combat allergies, excessive alcohol intake, stress, exposure to toxic substances, and other diseases.
Maintenance of a healthy gut flora is, however, dependent on many factors, especially the quality of food intake.
The official name of BMPR2 gene is bone morphogenetic protein receptor, type II (serine/threonine kinase).The BMPR2 gene provides instructions for making a protein called bone morphogenetic protein receptor. Bone morphogenetic protein receptor, type II spans the cell membrane, so that one end of the protein is on the outer surface of the cell and the other end remains inside the cell. This arrangement allows the protein to receive and transmit signals that help the cell respond to its environment by growing and dividing (cell proliferation) or by undergoing controlled cell death (apoptosis). This balance of cell proliferation and cell death regulates the number of cells in tissues.
Function:
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs
Location:
BMPR gene is present in human chromosome 2 and its coded from region 202,949,916 to 203,140,719 with 13 exons, the cytogenetic location 2q33-q34
Disease
Mutations in this gene have been associated with primary pulmonary hypertension, both familial and fenfluramine-associated, and with pulmonary venoocclusive disease.Researchers have identified more than 140 BMPR2 mutations that cause pulmonary arterial hypertension. About half of these mutations disrupt the assembly of bone morphogenetic protein receptor, type II, reducing the amount of this protein in cells. Other mutations prevent bone morphogenetic protein receptor, type II from reaching the cell surface, or alter its structure so it cannot receive or transmit signals.
It remains unclear how BMPR2 mutations cause pulmonary arterial hypertension. Researchers suggest that a mutation in this gene promotes cell proliferation or prevents cell death, resulting in an overgrowth of cells in the smallest arteries throughout the lungs. As a result, these arteries narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, pressure increases in the pulmonary artery and in the heart chamber that pumps blood into the pulmonary artery (the right ventricle). Signs and symptoms of pulmonary arterial hypertension occur when increased pressure cannot fully overcome the elevated resistance and blood flow to the body is insufficient.
Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the immune system attacks the central nervous system, leading to demyelination. Disease onset usually occurs in young adults, and it is more common in women. It has a prevalence that ranges between 2 and 150 per 100,000. MS was first described in 1868 by Jean-Martin Charcot.
MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are wrapped in an insulating substance called myelin. In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals. The name multiple sclerosis refers to scars (scleroses – better known as plaques or lesions) in the white matter of the brain and spinal cord, which is mainly composed of myelin.Although much is known about the mechanisms involved in the disease process, the cause remains unknown. Theories include genetics or infections. Different environmental risk factors have also been found.
Multiple sclerosis (MS) is a disease that affects the central nervous system. the CNS which consist of the brain spinal cord optic nerves everything we do whether it's taking a step to solving a problem or simply breathing relies on the proper functioning of the CNS.To understand how MS may impact the CNS we must explore the disease at the cellular level .In the brain millions of nerve cells called neurons continually send and receive signals, each signal is a minute but necessary part of the intricate CNS orchestrations that culminate in the actions, sensations, thoughts and emotions that comprised the human experience.Normally the path over which a nerve signal travels is protected by a type of insulation called the myelin sheath,this insulation is essential for nerve signals to reach their target.In MS the myelin sheath is eroded and the underlying wire like nerve fiber is also damaged, this leads to a breakdown in the ability of the nerve cells transmit signals. it is believed that the loss of myelin is the result of mistaken attack of immune cells.Immune cells protect the body against foreign substances such as bacteria and viruses .But in MS something goes awry.Immune cells infiltrate the brain and spinal cord seek and attack.As ongoing inflammation and tissue damage occurs nerve signals are disrupted. this causes unpredictable symptoms that can range from numbness or tingling to blindness and paralysis.These losses may be temporary or permanent
The official name of ALS2 gene is amyotrophic lateral sclerosis 2 (juvenile)..The ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. It is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.
Alsin's function in cells is unclear. It may play a role in regulating cell membrane organization and the movement of molecules inside cells. Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.
Location:
ALS2 gene is present in human chromosome 2 and ts coded from region 202,273,521 to 202,353,982 with 34 exons, the cytogenetic location 2q33.2
Disease
Mutation in the ALS2 Gene causes Amyotrophic lateral Sclerosis(ALS),infantile-onset ascending hereditary spastic paralysis ,juvenile primary lateral sclerosis.In all three disease mutations delete a single DNA building block (nucleotide), which alters the instructions for producing alsin. As a result, alsin is unstable and decays rapidly.
The official name of ALMS1 gene is Alstrom syndrome 1.The ALMS1 gene provides instructions for making a protein whose function is unknown. Researchers believe that the protein may play a role in hearing, vision, regulation of body weight, and functions of the heart, kidney, lungs, and liver. It may also affect how the pancreas regulates insulin, a hormone that helps control blood sugar levels.
The ALMS1 protein is present in most of the body's tissues, usually at low levels. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules, which are proteins that transport materials in cells and help the cell maintain its shape. The ALMS1 protein is also found at the base of cilia, which are finger-like projections that stick out from the surface of cells. Almost all cells have cilia at some stage of their life cycle. Cilia are involved in cell movement and many different chemical signaling pathways. Based on its location within cells, researchers suggest that the ALMS1 protein might be involved in the organization of microtubules, the transport of various materials, and the normal function of cilia.
Location:
ALMS1 gene is present in human chromosome 2 and ts coded from region 73,466,393 to 73,690,553 with 23 exons, the cytogenetic location 2p13
Disease
Mutation in the ALMS1 Gene causes Alström syndrome. Most of these mutations lead to the production of an abnormally small version of the ALMS1 protein that does not function properly. Researchers propose that a lack of normal ALMS1 function in the brain could lead to overeating. A loss of this protein in the pancreas may cause insulin resistance, a condition in which the body cannot use insulin properly. The combined effects of overeating and insulin resistance impair the body's ability to handle excess sugar, leading to diabetes and obesity (two common features of Alström syndrome). It is unclear how ALMS1 mutations cause the other signs and symptoms of Alström syndrome. Researchers suspect that this condition is associated with malfunctioning cilia in many of the body's tissues and organs.
The official name of AGXT gene is alanine-glyoxylate aminotransferase.The AGXT gene provides instructions for making a liver enzyme called alanine-glyoxylate aminotransferase gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes.This protein is important for several cellular activities such as ridding the cell of toxic substances and helping to break down certain fats. Peroxisomes contain several enzymes that are imported from the internal fluid of the cell (cytosol). Enzymes that are transferred into peroxisomes have a special arrangement of building blocks (amino acids) at one end of the enzyme that serves as a shipping address. In the peroxisome, alanine-glyoxylate aminotransferase converts a compound called glyoxylate to the amino acid glycine, which is later used for making enzymes and other proteins.
AGXT gene is present in human chromosome 2 and ts coded from region241456835 to 241467210 with 11 exons, the cytogenetic location 2q36-q37.
Disease
Mutation in the AGXT Gene causes type 1 primary hyperoxaluria. In some type 1 primary hyperoxaluria cases, alanine-glyoxylate aminotransferase enzyme activity is partially or entirely absent because of a mutation. As a result of this enzyme shortage, glyoxylate accumulates and is converted to a compound called oxalate instead of glycine. Oxalate, in turn, combines with calcium to form calcium oxalate, which the body cannot readily eliminate. Deposits of calcium oxalate can lead to kidney stones, kidney damage or failure, and injury to other organs, which are characteristic features of primary hyperoxaluria.
In other people with type 1 primary hyperoxaluria, the alanine-glyoxylate aminotransferase enzyme is misplaced within the cell. Misplacement occurs when certain mutations combine with a natural variation (polymorphism) in the gene. In most cases, a mutation replaces the amino acid glycine with the amino acid arginine at position 170 in the enzyme (written as Gly170Arg or G170R). This mutation occurs with a polymorphism that replaces the amino acid proline with the amino acid leucine at position 11 (written as Pro11Leu or P11L). The combined effect of the mutation and the polymorphism alters the structure of alanine-glyoxylate aminotransferase and changes the cellular shipping address of the enzyme. Instead of locating in peroxisomes, the enzyme is misdelivered to mitochondria, the energy-producing centers of cells. Even though the enzyme retains some of its activity, it cannot make contact with glyoxylate, which is located in peroxisomes. As a result, glyoxylate accumulates, leading to the signs and symptoms of primary hyperoxaluria.
Asexual reproduction is a form of reproduction where one parent is involved.A more stringent definition is agamogenesis which refers to reproduction without the fusion of gametes. Asexual reproduction is the primary form of reproduction for single-celled organisms such the archaea, bacteria, and protists. Many plants and fungi reproduce asexually as well.
Almost all bacterial cells reproduce by binary fission. As the term suggest this is process by which a single cell simply splits into two creating 2 identical copies of itself .the first step in this process is replication, At the replication stage bacteria increases in size and makes an exact duplicate of its chromosome following this bacteria begins to elongate and pinch off in the center. The two chromosomes moved to opposing sides of the cell and the cell wall grows to fill in the gap in the center. This results in two separate yet identical cells that are an exact match of the original parent cell
Maraviroc is a drug used in the treatment of HIV infection.Maraviroc is an entry inhibitor. Specifically, maraviroc blocks the chemokine receptor CCR5 which HIV uses as a co receptor to bind and enter a human helper T cell. Because HIV can also use another co receptor, CXCR4, an HIV tropism test such as a trofile assay must be performed to determine if the drug will be effective.
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 that allows the co-receptor binding this Binding triggers conformational changes in the GP 41 subunit leading to insertion of its N-terminal fusion peptide into the host cell's membrane.Fusion results release of the viral genome into the cytoplasm .the co-receptors are the members of the superfamily of G-protein coupled receptors over more than a dozen types of co-receptors have been described .But only two co-receptors such as areas of the CCR5 and CXCR4 are used by all HIV-1 strains. The co-receptors play a crucial role in HIV disease became evident when the common mutational variant of the CCR5 coding gene known as Delta 32 was discovered in 1996 This CCR5 genetic variant results in the production of nonfunctional CCR5 co receptors .The persons with two normal copies of the CCR5gene predominates in the population and are susceptible to HIV infection.The persons who inherit two copies of the CCR5 delta 32 variant from their parents known as delta 32 homozygotes of non functional CCR5 co receptors are appear to be highly resistant to HIV infection.Delta 32 homozygotes that appears not to be associated with any significant deleterious effects. Delta 32 heterozygotes inherit one copy of the CCR5 delta 32 variant from one parent in the normal form of the CCR5gene from the other parent, Delta 32 heterozygotes can become infected with HIV disease progression is significantly delayed compared to those who have two normal copies of the CCR5 gene. To be effective the co receptor antagonist must be directed at a specific co-receptor CCR5 ,THE co-receptor antagonist for example functions by binding specifically to the CCR5 co receptor molecule, The bound co-receptor is blocked from binding the viral GP 120 subunit which prevents the conformational changes on GP 41 which prevents viral particle entry and HIV particles are unable to enter the T cell cannot infected and cannot replicate. Different HIV strains vary in their ability to use the major co-receptors to achieve entry into the host cell some HIV strains easily use CCR5 co receptor summoning the CX Cr4 for a receptor while other viruses geotropic use both. In HIV-infected individual may have only the CCR5 using virus or the CXCR4 using virus or a mixture of CCR5 using CXCR4 using duo tropic viruses.In the early phase of infection the CCR5 using virus predominates in most patients in the late phase of infection HIV strains capable of using CXCR4 recptoe. Unlike reverse transcripase or protease inhibitors which went inside the infected cell to receptor ,Antagonists function on the outside of the host cell,The co-receptor antagonists are therefore classified as entry inhibitors. the mechanism of action of co-receptor antagonists differs from other antiretroviral in a very important way rather than binding to viral proteins this new class prevents viral replication by binding to human cells such as T cells and macrophages this unique mechanism has potential clinical advantages.
The official name of ABCG8 is ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2).The ABCG8 gene provides instructions for making a Sterolin-2 protein.Sterolin-1 and –2 are two ‘half’ adenosine triphosphate binding (ATP) cassette (ABC) transporters which found to be indispensable for the regulation of sterol absorption and excretion.The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions to exclude non-cholesterol sterol entry at the intestinal level, promote excretion of cholesterol and sterols into bile, and to facilitate transport of sterols back into the intestinal lumen. It is expressed in a tissue-specific manner in the liver, intestine, and gallbladder. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5.
Location:
ABCG5 gene is present in human chromosome 2 and ts coded from region 43919607 to 43959109 complement with 13 exons, the cytogenetic location 2p21.
Disease
Mutations in both alleles of either ABCG5 or ABCG8 in the human results in sitosterolemia. Sitosterolemia (also known as phytosterolemia) is a rare autosomal recessively inherited lipid metabolic disorder characterized by the presence of tendon xanthomas, premature coronary artery disease and atherosclerotic disease, hemolytic episodes, arthralgias and arthritis. The hallmark of sitosterolemia is diagnostically elevated levels of plant sterols in the plasma.
The official name of ABCG5 is ATP-binding cassette, sub-family G (WHITE), member 5.The ABCG5 gene provides instructions for making a sterolin1 protein OF ABC group proteins. Sterolin-1 and –2 are two ‘half’ adenosine triphosphate binding (ATP) cassette (ABC) transporters which found to be indispensable for the regulation of sterol absorption and excretion.
Location:
ABCG5 gene is present in human chromosome 2 and ts coded from region 43893115 to 43919462 complement with 13 exons, the cytogenetic location 2p21.
Disease
Mutations in both alleles of either ABCG5 or ABCG8 in the human results in sitosterolemia. Sitosterolemia (also known as phytosterolemia) is a rare autosomal recessively inherited lipid metabolic disorder characterized by the presence of tendon xanthomas, premature coronary artery disease and atherosclerotic disease, hemolytic episodes, arthralgias and arthritis. The hallmark of sitosterolemia is diagnostically elevated levels of plant sterols in the plasma.
Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure.
The skin normally forms a protective barrier between the body and its surrounding environment. The skin abnormalities associated with harlequin ichthyosis disrupt this barrier, making it more difficult for affected infants to control water loss, regulate their body temperature, and fight infections. Infants with harlequin ichthyosis often experience an excessive loss of fluids (dehydration) and develop life-threatening infections in the first few weeks of life. It used to be very rare for affected infants to survive the newborn period. However, with intensive medical support and improved treatment, people with this disorder now have a better chance of living into childhood and adolescence.
Harlequin ichthyosis is very rare; its exact incidence is unknown.
Genes are related to harlequin ichthyosis
Mutations in the ABCA12 gene cause harlequin ichthyosis. The ABCA12 gene provides instructions for making a protein that is essential for the normal development of skin cells. This protein plays a major role in the transport of fats (lipids) in the outermost layer of skin (the epidermis). Some mutations in the ABCA12 gene prevent the cell from making any ABCA12 protein. Other mutations lead to the production of an abnormally small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein disrupts the normal development of the epidermis, resulting in the hard, thick scales characteristic of harlequin ichthyosis.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Treatment Information about harlequin ichthyosis:
Gene Review: Autosomal Recessive Congenital Ichthyosis
The official name of ABCA12 is ATP-binding cassette, sub-family A (ABC1), member 12.The USH2A gene provides instructions for making a protein called ATP-binding cassette (ABC) transporter. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants.
Location:
USH2A gene is present in human chromosome 2 and ts coded from region 215504511 to 215711396 complement with 53 exons, the cytogenetic location 2q34.
Disease
Mutations iin the ABCA12 gene have been identified in people with harlequin ichthyosis. Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure.ABCA12 gene mutations probably lead to an absence of ABCA12 protein or the production of an extremely small version of the protein that cannot transport lipids properly. A lack of lipid transport causes numerous problems with the development of the epidermis before and after birth. Specifically, it prevents the skin from forming an effective barrier against fluid loss (dehydration) and infections, and leads to the formation of hard, thick scales characteristic of harlequin ichthyosis.
The below Video is in very disturbing.I added this video only to show how cruel this disorder is.
Deoxyribonucleic acid (DNA) is a nucleic acid molecule consisting of long chains of polymerized (deoxyribo) nucleotides. In double-stranded DNA the two strands are held together by hydrogen bonds between complementary nucleotide base pairs.
DNA was discovered in 1869 by Johann Friedrich Miescher, a Swiss biochemist working in Tubigen, Germany, The first extracts that Miescher made from human white blood cells were crude mixtures of DNA and chromosomal proteins. Next year he prepared a pure sample of nucleic acid from Salomon sperm, The chemical test showed that DNA is acidic and rich in phosphorus, and also suggested that the individual molecules are very large, although it was not until the 1930s when biophysical techniques are applied to DNA that huge lengths of polymeric chains were fully appreciated.
The basic building block of nucleic acids is the nucleotide. This has three components:
a nitrogenous base;
a sugar;
and a phosphate.
The nitrogenous base is a purine or pyrimidine ring. The base is linked to position 1 on a pentose sugar by a glycosidic bond from N1 of pyrimidines or N9 of purines. To avoid ambiguity between the numbering systems of the heterocyclic rings and the sugar, positions on the pentose are given a prime ().
Nucleic acids are named for the type of sugar; DNA has 2–deoxyribose, whereas RNA has ribose. The difference is that the sugar in RNA has an OH group at the 2 position of the pentose ring. The sugar can be linked by its 5 or 3 position to a phosphate group.
A nucleic acid consists of a long chain of nucleotides. the backbone of the polynucleotide chain consists of an alternating series of pentose (sugar) and phosphate residues. This is constructed by linking the 5 position of one pentose ring to the 3 position of the next pentose ring via a phosphate group. So the sugar-phosphate backbone is said to consist of 5–3 phosphodiester linkages. The nitrogenous bases "stick out" from the backbone.
Each nucleic acid contains 4 types of base. The same two purines, adenine and guanine, are present in both DNA and RNA. The two pyrimidines in DNA are cytosine and thymine; in RNA uracil is found instead of thymine. The only difference between uracil and thymine is the presence of a methyl substituent at position C5. The bases are usually referred to by their initial letters. DNA contains A, G, C, T, while RNA contains A, G, C, U.
The terminal nucleotide at one end of the chain has a free 5 group; the terminal nucleotide at the other end has a free 3 group. It is conventional to write nucleic acid sequences in the 5→3 direction—that is, from the 5 terminus at the left to the 3 terminus at the right.
The replication process is initiated at particular points within the DNA, known as "origins", which are targeted by proteins that separate the two strands and initiate DNA synthesis.Origins contain DNA sequences recognized by replication initiator proteins (eg. dnaA in E coli' and the Origin Recognition Complex in yeast). These initiator proteins recruit other proteins to separate the two strands and initiate replication forks.
Initiator proteins recruit other proteins to separate the DNA strands at the origin, forming a bubble. Origins tend to be "AT-rich" (rich in adenine and thymine bases) to assist this process because A-T base pairs have two hydrogen bonds (rather than the three formed in a C-G pair)—strands rich in these nucleotides are generally easier to separate. Once strands are separated, RNA primers are created on the template strands and DNA polymerase extends these to create newly synthesized DNA.
As DNA synthesis continues, the original DNA strands continue to unwind on each side of the bubble, forming replication forks. In bacteria, which have a single origin of replication on their circular chromosome, this process eventually creates a "theta structure" (resembling the Greek letter theta: θ). In contrast, eukaryotes have longer linear chromosomes and initiate replication at multiple origins within these.
The replication fork
The replication fork is a structure which forms when DNA is being replicated. It is created through the action of helicase, which breaks the hydrogen bonds holding the two DNA strands together. The resulting structure has two branching "prongs", each one made up of a single strand of DNA.
Leading strand synthesis
In DNA replication, the leading strand is defined as the new DNA strand at the replication fork that is synthesized in the 5'→3' direction in a continuous manner. When the enzyme helicase unwinds DNA, two single stranded regions of DNA (the "replication fork") form. On the leading strand DNA polymerase III is able to synthesize DNA using the free 3' OH group donated by a single RNA primer and continuous synthesis occurs in the direction in which the replication fork is moving.
Lagging strand synthesis
The lagging strand is the DNA strand at the opposite side of the replication fork from the leading strand, running in the 3' to 5' direction. Because DNA polymerase cannot synthesize in the 3'→5' direction, the lagging strand is synthesized in short segments known as Okazaki fragments. Along the lagging strand's template, primase builds RNA primers in short bursts. DNA polymerases are then able to use the free 3' OH groups on the RNA primers to synthesize DNA in the 5'→3' direction. The RNA fragments are then removed (different mechanisms are used in eukaryotes and prokaryotes) and new deoxyribonucleotides are added to fill the gaps where the RNA was present. DNA ligase then joins the deoxyribonucleotides together, completing the synthesis of the lagging strand.
Text source:
Endometrium is the inside lining of the uterus,Endometrial Biopsy is the removal of the sample of the tissue from the endometrium for testing ,A biopsy may be done for examine the cells are where cancer or precancerous cells,to determine the cause of irregular bleeding or to investigate fertility problems,this procedure also used find infection and monitor medication effectiveness
The patient will be asked to undress and lie on the table with her feet in the stirrups for a pelvic examination. She may or may not be given localized anesthesia.
A speculum will be inserted into the vagina to spread the walls of the vagina apart to expose the cervix.The cervix will then be cleansed with an antiseptic solution.
A tenaculum, a type of forceps, will hold the cervix steady for the biopsy.
A pipelle, a thin tube also called a catheter, will be inserted into the uterus. A smaller tube (internal piston) inside the pipelle will be withdrawn to create suction. The pipelle be will rotated and moved in and out to collect small pieces of endometrial tissue. Cramping may occur.
The removed tissue will be placed in a preservative.
The tissue will be sent to a laboratory, where it will be processed and tested. It will then be read microscopically by a pathologist who will determine the diagnosis
Heralded as the future of medicine, personalized medicines seem to be the answer for making therapeutics more likely to be highly effective and safer. Join Deanna Kroetz of UCSF's School of Pharmacy and learn about macromolecular therapeutics, their promise, their limitations.
Pharmacogenetics is the study or clinical testing of genetic variation that gives rise to differing response to drugs.Much of current clinical interest is at the level of pharmacogenetics, involving variation in genes involved in, drug metabolism with a particular emphasis on improving drug safety. The wider use of pharmacogenetic testing is viewed by many as an outstanding opportunity to improve prescribing safety and efficacy. Driving this trend are the 106,000 deaths and 2.2 Million serious events caused by adverse drug reactions in the US each year (Lazarou 1998). As such ADRs are responsible for 5-7% of hospital admissions in the US and Europe, lead to the withdrawal of 4% of new medicines and cost society an amount equal to the costs of drug treatment (Ingelman-Sundberg 2005). Comparisons of the list of drugs most commonly implicated in adverse drug reactions with the list of metabolizing enzymes with known polymorphisms found that drugs commonly involved in adverse drug reactions were also those that were metabolized by enzymes with known polymorphisms
Blood pressure or BP is the pressure exerted by the flow of blood on the walls of the arteries; it is determined by the force and amount blood pumped by the heart and by diameter of the arteries. it consist of the two components systolic pressure and diastolic pressure, these are normally 120/80 mgof mercury respectively, when the blood pressure exceed these value it leads to a condition called high blood pressure or hypertension, there are two types of hypertension primary hypertension and secondary hypertension, primary hypertension is without specific identifiable cause, secondary hypertension is elevated blood pressure that results from underlying identifiable often correctable cause, only about 5 to10 % hypertension cases are thought to result from secondary causes, the most common causes of the secondary hypertension are kidney disease ,adrenal gland disease, narrowing of the aorta and sleep apnea, Hypertension common symptoms are Headache,Dizziness,Blurred vision, and in severe cases confusion and coma are possible. Small portable instruments called a sphygmomanometer usually measure Blood pressure, It consist of an air pump, pressure gauge and rubber cuff. The instrument measures the blood pressure in units called millimeter of mercury (mmhg). A blood pressure reading of 120/80mmHg is considered normal, where as the blood pressure of 140/90mmHg or higher is considered High Blood pressure or Hypertension
Most of the secondary mechanisms associated with hypertension are generally fully understood, and are outlined at secondary hypertension. However, those associated with essential (primary) hypertension are far less understood. What is known is that cardiac output is raised early in the disease course, with total peripheral resistance (TPR) normal; over time cardiac output drops to normal levels but TPR is increased. Three theories have been proposed to explain this:
Inability of the kidneys to excrete sodium, resulting in natriuretic factors such as Atrial Natriuretic Factor being secreted to promote salt excretion with the side-effect of raising total peripheral resistance.
An overactive renin / angiotensin system leads to vasoconstriction and retention of sodium and water. The increase in blood volume leads to hypertension.
An overactive sympathetic nervous system, leading to increased stress responses.
It is also known that hypertension is highly heritable and polygenic (caused by more than one gene) and a few candidate genes have been postulated in the etiology of this condition.
Prevention:
Prevention of hypertension only goes as far as the cause; one can adjust lifestyle related causes but genetics, race, age and gender are outside the realm of change.
Modifiable factors include diet, weight-loss, exercise and stress management.
Low-sodium and low-fat diets can reduce cardiovascular risks and keep arteries clear of plaque and blood volume at normal levels.
Losing even 10% of body weight can have fantastic benefits towards health, including reversal or prevention of HTN, dropping systolic pressures several points.
Exercise maintains a healthy heart, thus healthy cardiac contractions and functions. The heart is a muscle too, working out the cardiac muscles makes the heart beat more efficiently, thus pumping blood around the body more effectively.
Stressors can negatively affect blood pressure by activating the sympathetic nervous system, thus fight or flight responses which increase heartrate and blood pressure. Chronic stress can lead to regular and frequent activation of the system and repeated high blood pressure.
Effective management of stress can reduce this particular risk.
The official name of USH2A gene is Usher syndrome 2A (autosomal recessive, mild)..The USH2A gene provides instructions for making anan enzyme called usherin. Usherin is an important component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Usherin is found in the inner ear and the part of the eye that detects light and color (the retina). Although the function of usherin has not been well established, studies suggest that this protein is part of a larger protein complex that plays an important role in inner ear and retinal development. In these locations, the protein complex may also be involved in the function of synapses, which are junctions between nerve cells where cell-to-cell communication occurs.
Location:
USH2A gene is present in human chromosome 1 and ts coded from region 213,862,858 to 214,663,360 complement with 71 exons, the cytogenetic location 1q41.
Disease
Mutations in USH2A gene causes a form of Usher syndrome type IIA,Usher syndrome is a condition characterized by hearing loss or deafness and progressive vision loss. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate.Mutations change single protein building blocks (amino acids) in the usherin protein. In some cases, these mutations lead to the production of an abnormally short version of the protein or prevent the cell from making any functional usherin. Other mutations insert or delete small amounts of DNA in the USH2A gene, which probably impairs the normal function of usherin. Researchers have not determined how a missing or altered usherin protein leads to the signs and symptoms of Usher syndrome.The most common mutation in the USH2A gene is found in about 25 percent of people with Usher syndrome type IIA, particularly those from Europe, the United States, South Africa, and China. This mutation deletes a specific DNA building block, a guanine (G) nucleotide, at position 2299 in the USH2A gene (written as 2299delG). Individuals with this change, or with similar mutations in the USH2A gene, develop moderate to severe hearing loss and retinitis pigmentosa, a disorder that results in loss of vision.
The official name of UROD gene is uroporphyrinogen decarboxylase.The UROD gene provides instructions for making anan enzyme called uroporphyrinogen decarboxylase. Uroporphyrinogen III decarboxylase (UroD) is a homodimeric enzyme which catalyzes the fifth step in heme biosynthesis: the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III.Three additional enzymes modify this product before it becomes heme. The heme molecule is then incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.
Location:
UROD gene is present in human chromosome 1 and ts coded from region 45250417 to 45253928 with 10 exons, the cytogenetic location 1p34.
Disease
Mutations in UROD gene causes a form of porphyria called porphyria cutanea tarda and hepatoerythropoietic porphyria,In porphyria cutanea tarda the mutations occur in one of the two copies of the UROD gene in each cell, which usually reduces the activity of uroporphyrinogen decarboxylase by 50 percent throughout the body.As a result, byproducts of heme production called porphyrins build up in the body, particularly in the liver. This buildup, in combination with nongenetic factors (such as alcohol, smoking, certain hormones, excess iron, and viral infections), causes this type of porphyria.
In hepatoerythropoietic porphyria Most of the mutations are unique in this type of porphyria and have not been found in porphyria cutanea tarda. Mutations that cause hepatoerythropoietic porphyria occur in both copies of the UROD gene in each cell, which reduces the activity of uroporphyrinogen decarboxylase to less than 10 percent of normal. Extremely low levels of this enzyme prevent sufficient amounts of heme from being produced. As a result, byproducts of heme production called porphyrins build up in the body, causing this type of porphyria.
Natural selection is the process by which favorable heritable traits become more common in sucessiove genrations of a population of reproducing organisms,and unfavorable heritable traits become less common, due to differntial reproduction of genotypes,Natural selection acts on the phenotype, or the observable characteristics of an organism, such that individuals with favorable phenotypes are more likely to survive and reproduce than those with less favorable phenotypes. The phenotype's genetic basis, genotype associated with the favorable phenotype, will increase in frequency over the following generations. Over time, this process may result in adaptations that specialize organisms for particular ecological niches and may eventually result in the emergence of new species. In other words, natural selection is the mechanism by which evolution may take place in a population of a specific organism.The term was introduced by Charles Darwin in his groundbreaking 1859 book The Origin of Species in which natural selection was described by analogy to artificial selection, a process by which animals with traits considered desirable by human breeders are systematically favored for reproduction. The concept of natural selection was originally developed in the absence of a valid theory of inheritance; at the time of Darwin's writing, nothing was known of modern genetics. Although Gregor Mendel, the father of modern genetics, was a contemporary of Darwin's, his work would lie in obscurity until the early 20th century. The union of traditional Darwinian evolution with subsequent discoveries in classical and molecular genetics is termed the modern evolutionary synthesis. Although other mechanisms of molecular evolution, such as the neutral theory advanced by Motoo Kimura, have been identified as important causes of genetic diversity, natural selection remains the single primary explanation for adaptive evolution.
This lecture was conducted by Dr.Bisola 0 0jikutu MD M.P.H Director of the Office of International Programs Division of AIDS, Harvard Medical School,She working has a infectious disease specialist ,concentrating on AIDs disease.She talks about HIV Drugs and HIV Evolution (how HIV got resistant against hiv drugs) and various anti-retroviral drugs, such as AZT,Protease inhibitor and HAART and its mechanism ,which had been used to prevent HIV infection. She also tells how Hiv became resistant to these drugs and concludes with latest HIV drug MARAVIROC and how it might prevent HIV infection
Most people who are infected with Hiv virus will develop AIDS, The Disease is caused by decrease in Helper T cells count and increase in viral level. Once they develop Aids the Patient will have opportunistic infection. And eventually leads to death.To stop the disease the viral replication should stopped.
Aids infection was first noticed in 1981 and virus was Cultured 1983 .In 1985 commercial test done to detect Hiv antibody, After 6 years medication for HIV is found,The Medication was called AZT (azidothymidine), so what is AZT .
AZT
AZT is a similar analog of thiamine, which is building block of DNA.Difference between AZT and thymine is that AZT has azide side chain rather than hydroxyl chain of thyimidine.
History of AZT
Back in 1960s AZT was synthesized for treating cancer, but it Was unable to prevent cancer, so it was put is shelf, and When HIV came researchers thought "y don't we try this drug for treating HIV”.
Mode of Action of AZT
Generally HIV RNA reverse transcribed to a growing strand DNA, During reverse transcription nucleotides bind to this Growing strand of DNA,When AZT comes in, it looks like a nucleotide ,and binds to the hydroxyl group, But it has azide side chain which blocks further extension of the chain because of this other nucleotides cannot bind to it.
AZT Clinical trial
In Phase 1 AZT clinical trial, they had given AZT to HIV patients for six weeks, they found significant increase of T-helper cells in patient. In phase 2 trials AZT was compared to placebo(a inactive drug that generally used for comparison) In this patients with AZT had low proportion of opportunistic infection than people who had taken placebo.The striking thing in trial is mortality rate, In treatment group who took AZT 1 in 145 people died,but in placebo group 16 out of 137 people died. After 7 months researchers halted the Trial and unblinded it(now patients and researchers now know which drug they are taking) and because of the striking result everybody started to have AZT .The problem with drug was there was increase in Viral level after 22 weeks, that is HIV got resisted to this drug after 22 weeks.
AZT Resistance
The reason behind the HIV got resistant against AZT is that ,when HIV RNA is reverse transcribed to the growing DNA strand,Reverse trascriptase makes lot of errors,so in patients blood we can see lot mutant HIV Virus,so when AZT is given to patients it lowers the amount virus in the blood, But the virus is still replicates it doesn't lowers enough,When you keepon giving the drug ,under the selective pressure HIV virus starts developing more resistant virus.
Protease Enzyme
When HIV buds from the cell, it is not in the matured form,protease enzyme cleves the this unmatured protein in several places so the unmaturatured protein undergoes confirmation changes to make matured HIV virus
Mode of Action of Protease inhibitor
When protease inhibitor enters into cell , The inhibitor bind to the active site in protease enzyme,because of this protease enzymes is unable to cleave the proteins,which inturn result on-maturation of HIV virus
HAART therapy:
Two drugs won't for very long in preventing HIV, So if u give three dugs (2 of AZT type+1 protease inhibitor) we can see sustained decrease in HIV virus in blood and increase in T-helper cells level
CCR5
Researcher found that Certain people are not affected by HIV though they had repeated exposure to HIV virus. One hypothesis researchers told These people would have some genetic mutation in immune system, which stops HIV to entering into the cells. Researchers found that these people had small CCR5 receptor (chemokine co-receptor) in T-helper cells, which makes HIV not able to enter the cell. This makes to good drug target,If we able to inhibit CCR5 receptor then HIV virus will be unable to enter the cell.
Semi conservative replication is a normal process of DNA synthesis, in which the two original strands of the molecule separate, and each acts as a template on which a new complementary strand is laid down.
The genetic information in a bacterial cell is stored in the form of a double stranded covalently closed circle of DNA; Replication begins at a specific site called the origin. The origin replicates and then DNA replication proceeds in two directions, the two original strands shown as solid lines serve as the templates for synthesis of new strands, shown as dotted line, this refereed to as semi conservative replication
Synaptic transmission is the process whereby one neuron (nerve cell) communicates with other neurons or effectors, such as a muscle cell, at a synapse. A typical neuron has a cell body (soma), branching processes specialized to receive incoming signals (dendrites), and a single process (axon) that carries electrical signals away from the neuron toward other neurons or effectors. Electrical signals carried by axons are action potentials. Axons often have thousands of terminal branches, each ending as a bulbous enlargement, the synaptic knob or synaptic terminal. At the synaptic knob, the action potential is converted into a chemical message which, in turn, interacts with the recipient neuron or effector. This process is synaptic transmission.
Information has to travel from one neuron to next, it must be transferred across synaptic cleft, neuro transmitters are chemical messengers that bridge the gap formed by synapes, neurotransmitters are stored in synaptic vesicles at the end of axons. As the action potential reaches the terminal end of the axon, calcium influx through the calcium channels causes these vesicles to fuse with pre-synaptic membrane, the vesicles then dump their contents which are neuro transmitters into the synaptic cleft, the neuro transmitters then diffuse with the post synaptic membrane and bind to specific receptors, however neuro transmitters only act for the brief time, their action is terminated by reuptake pumps that force neurotransmitters back into axon terminal or sometimes by enzymatic degradation in the synaptic cleft ,this removes the neurotransmitters from the synaptic cleft and terminates its effect on post synaptic membrane. Animation showing neurotransmission across the synaptic cleft.
Th Origin species was published in year 1859 by Charles Darwin ,It introduced the theory that populations evolve over the course of generations through a process of natural selection,Darwin's book was the culmination of evidence he had accumulated on the voyage of the Beagle in the 1830s and expanded through continuing investigations and experiments after his return.
Darwin's theory is based on key observations and inferences drawn from them:
Species have great fertility. They have more offspring than can grow to adulthood.
Populations remain roughly the same size, with small changes.
Food resources are limited, but are relatively stable over time.
An implicit struggle for survival ensues.
In sexually reproducing species, generally no two individuals are identical.
Some of these variations directly impact the ability of an individual to survive in a given environment.
Much of this variation is inheritable.
Individuals less suited to the environment are less likely to survive and less likely to reproduce, while individuals more suited to the environment are more likely to survive and more likely to reproduce.
The individuals that survive are most likely to leave their inheritable traits to future generations.
This slowly effected process results in populations that adapt to the environment over time, and ultimately, after interminable generations, these variations accumulate to form new varieties, and ultimately, new species.
Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Although raised intraocular pressure is a significant risk factor for developing glaucoma, there is no set threshold for intraocular pressure that causes glaucoma. One person may develop nerve damage at a relatively low pressure, while another person may have high eye pressure for years and yet never develop damage. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness.
Glaucoma has been nicknamed the "sneaky thief of sight" because the loss of visual field often occurs gradually over a long time and may only be recognized when it is already quite advanced. Once lost, this damaged visual field can never be recovered. Worldwide, it is the second leading cause of blindness. Glaucoma affects one in two hundred people aged fifty and younger, and one in ten over the age of eighty.
The major risk factor for most glaucomas and focus of modeling and treatment is increased intraocular pressure. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary body of the eye and its drainage through the trabecular meshwork. Aqueous humor flows from the ciliary bodies into the posterior chamber, bounded posteriorly by the lens and the zonule of Zinn and anteriorly by the iris. It then flows through the pupil of the iris into the anterior chamber, bounded posteriorly by the iris and anteriorly by the cornea. From here the trabecular meshwork drains aqueous humor via Schlemm's canal into scleral plexuses and general blood circulation. In open angle glaucoma there is reduced flow through the trabecular meshwork; in angle closure glaucoma, the iris is pushed forward against the trabecular meshwork, blocking fluid from escaping.
The inconsistent relationship of glaucomatous optic neuropathy with ocular hypertension has provoked hypotheses and studies on anatomic structure, eye development, nerve compression trauma, optic nerve blood flow, excitatory neurotransmitter, trophic factor, retinal ganglion cell/axon degeneration, glial support cell, immune, and aging mechanisms of neuron loss.
Column chromatography in chemistry is a method used to purify individual chemical compounds from mixtures of compounds. It is often used for preparative applications on scales from micrograms up to kilograms.
The classical preparative chromatography column is a glass tube with a diameter from 5 to 50 mm and a height of 50 cm to 1 m with a tap at the bottom. A slurry is prepared of the eluent with the stationary phase powder and then carefully poured into the column. Care must be taken to avoid air bubbles. A solution of the organic material is pipetted on top of the stationary phase. This layer is usually topped with a small layer of sand or with cotton or glass wool to protect the shape of the organic layer from the velocity of newly added eluant. Eluant is slowly passed through the column to advance the organic material. Often a spherical eluent reservoir or an eluent-filled and stoppered separating funnel is put on top of the column.
Subscribe in a reader Steps involved: During chromatography support or matrix is placed in the column,the support is equilibrated with the buffer which is generally identical to buffer in which the sample is dissolved
and sample is applied to the column,in most chromotograhy protocols the protein of interest along with the protein impurities in the sample find to the matrix,the impuritis are washed away by the buffer ,which usually the same buffer which is used in equilibration,then sample is then eluded and collected by washed with appropriate buffer,if teh single buffer is used the process is reffered to as isocratic separation,if multiple buffers are used its is called has gradient,the support is then washed by regeneration buffer that prepares th column for further use and storage with exception of gel filteration ,this basic protocal is used
Anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicyclomine. Generally speaking, it reduces the effects mediated by acetylcholine on acetylcholine receptors in neurons through competitive inhibition. The effect is therefore reversible.
By blocking parasympatc neruo transmittor acetocholine ,anti-cholorinergic drugs promote bronchoconstrictiction,the vagus nerve along the airways release acetylcholine which binds with muscarinic receptors in the smooth muscle and airway sub mucosal glands,by blocking acetylcholine anticholiergics contradict bronchoconstriction
National Symposium on HIV/AIDS Prevention & Transmission 2007, you will hear from experts from universities throughout the US and from South Africa, updating us on their latest research and findings. Join Eliezer Masliah, MD, University of California, San Diego, as he presents on Changing Aspects of the Neuropathogenesis of HIV in the HAART Era.
Diagnostic pelvic laproscopy is used to examine the internal organs of pelvis in an effort to identify the specific problem,he may advised to undergo diagnostic laproscpy for example if u have Pelvic pain or mass,an abnormal accumulation of fluid or difficulty in becoming pregnant. Laparoscopy is usually performed under general anesthesia; however it can be performed with other types of anesthesia that permit the patient to remain awake.
The typical pelvic laparoscopy involves a small (1/2" to 3/4") incision in the belly button or lower abdomen. The abdominal cavity is filled with carbon dioxide. Carbon dioxide causes the abdomen to swell which lifts the abdominal wall away from the internal organs, so the doctor has more room to work.
Next, a laparoscope (a one-half inch fiber-optic rod with a light source and video camera) is inserted through the belly button. The video camera permits the surgeon to see inside the abdominal area on video monitors located in the operating room.
Depending on the reason for the laparoscopy, the physician may perform surgery through the laparoscope by inserting various instruments into the laparoscope while using the video monitor as a guide. The video camera also allows the surgeon to take pictures of any problem areas he discovers.
