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.
Scope this lecture continues their discretion of mentors contribution to genetics turned and the subsequent experiments in which Mendel looked at the transmission of more than one trait, leading to an of independent assortment. The lecture summarizes in the wind us up and, linkage, and crossover, all of which result from the way chromosome and the gene located on them move during gamete formation and sexual reproduction. The lecture concludes by recapping the sources that contribute to genetic variation that is essential for evolution to occur.
Outline
I. Mendel continued his space experiment by crossing pea plants that are too phenotypic differences instead of one. From these dihybrid crosses, Mendel inferred additional properties of three transmission from the parents to offspring, properties consistent with knowledge gained later the moment of genes on chromosomes.
A. as wit flower color, seed color in pea plants depend on the single gene with two alleles: the Dominant yellow allele(Y) in the recessive gene allele(y).
B. space for example, when crossing the female pea plant with purple flowers and yellow seeds with the male pea plant with white flowers and green seats, we know that females genotype is PPYY in the male genotype is ppyy.
C.F1 individuals will have purple flower and a yellow seeds, because they are all heterozygous for both traits. As in monohybrid cross, the recessive traits disappeared in F1.
D. when F1 individuals makes gametes, do the allels from the original parents stay together or are they separated next?
If parent alleles are linked, an F1 space individual could produce only PY and py gametes;F2 would then contain only two parental phenotypes. Furthermore, these people takes would have the same 3:1 ratio as in monohybrid cross. This would mean that sets of parent alleles acted as a single alleles.
If parental alleles are not linked,F1 individuals would produce for better gamete in equal proportions:PY,py,Py,pY. A punnet Square using these gametes asserting 16 possible combinations and 9 distinctive F2 genotypes. These nine genotypes would produce 4 possible phenotypes, which would occur in 9: 3:3:1 ratio. Two of these phenotypes would not have existed in parent the generation; these so-called recombinant phenotypes.
Mendel observed 4 phenotypes in a 9:3:3:1 ratio in his F2 generation, which he correctly concluded to mean that alleles of inherited independently of each other.
E. from this conclusion, mendel formatted what is known as law of independent assortment, which simply says that Alleles off different genes segregating independently of each other during gamete formation.
II. Integral assortment of genes during meiosis is an important source of genetic variation.
During first meiotic division, homologues chromosomes line up in the cell and separated into two daughter cells. The assortment of Maternal and parent homology’s for1 chromosome has more effect on the assortment of any other chromosome.
In the genes of two different traits are on different chromosomes, they will assort independently of each other, as Mendel saw, and independent assortment produce recombinant phenotypes.
The number of unique combination of alleles on different chromosome can be very. Humans have 23 pairs of chromosomes; the possible number of assortment is 2(23) or about 8.4 million.
Independent assortment is different from mutation as a source of variation.
Mutation essentially generates new alleles-usually dysfunctional but not always.
Independent assortment does not create new alleles but, rather, new assortment of alleles.
However, both mutation and Independent assortment can change their phenotypes of successive generations.
III. if two genes occur on the same chromosome, an obvious conclusion is that they will be transmitted together as a unit during meiosis. Such genes are called linked genes.
During meiosis, however, homologue pairs of chromosomes associated so closely that they can exchange genetic material, which called crossing over. If linked gene crossover to other chromosome, they can assort independently.
Geneticists expanding on Mendel's work found that in the Everett tosses, F2 generation with linked genes would occasionally produce recombinant phenotypes, though a far fewer number than if the genes unlinked. Link genes, however, should not produce any recombinant phenotypes.
The further apart to genes on the chromosome, the more likely crossing over and recombinant phenotypes with be.
IV. Space though essentially established the sciences of genetics, Mendel’s work was ignored for about 40 years, because nothing was then known of the physical basis of mentors heritable factors and because he used advanced probability mathematics to calculate is ratio. Only when biologists began to see the pattern Mendel described did anyone realize that this work might be significant.
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
In today's lecture what I want to do is to look at a little bit of detail at how the connection between Genes and chromosomes was forged.
Chromosomes had not been described when Mendel lived and worked, it was only later with the advent of improved microscopes in the second part of the 19th century of biologists began to describe the structure of cells in some detail, and one of the things they noticed was the formation of dark bodies in the nucleus of cells that would appear just before cells divide and furthermore they notice that as cells were dividing these dark bodies would fall peculiar movement. What they were seeing were chromosomes and movements of these chromosomes in mitosis and meiosis.
The significance of the movements of these chromosomes wasn't appreciated at first but then in the early 20th century two-cell biologist independently had an insight Walter Sutton and colleague observed that the highly choreographed movements of chromosomes during meiosis reduced by half number of chromosomes that would be found in gametes. When gametes joined the total number of chromosomes would come back up to its full complement. They realize that this reduction in chromosome number in gametes formation and subsequent restoration zygote formation could explain the patterns of trait transmission that Mendel had described with his laws of segregation and independent assortment.
In 1903 Sutton and Bovary both independently publish their ideas, which become generally known as the chromosomal theory of inheritance. in that sense they provided a hypothetical mechanism whereby chromosome movements could completely explain these two fundamental principles that Mendel had suggested.
The chromosomal theory of inheritance should seem obvious to us at this point in the course because we are to know so much about DNA learn that before but it wasn't clear then that you could establish this relationship specifically it wasn't clear how during the early part of the 20th century you could prove that genes were on chromosomes and thus prove the chromosome theory of inheritance, sutten & Bovary had suggested this connection but it was just a hypothesis. Confirmation of this hypothesis actually can be attributed to one particular scientist and a remarkable lab group and also to the particular organism, the scientist was Thomas Hunt Morgan who was a embryologist studying patterns of development working at Columbia University.
Like most biologist at the time Morgan to became interested in mechanisms of inheritance that as people began to talk again about Mendel's work .Now Morgan was particularly interested as he was studying development in mutations, and he was interested in how new mutations arose in organisms. Many geneticists at the time had begun working on organisms that had more complex patterns of trait transmission than for example the garden peas Mendel worked on including for example small mammals such as guinea pigs and mice because the way that her color patterns of these mammals would be transmitted from parent to offspring sometimes corresponded to what Mendel observed that also led to a lot of interesting exceptions that these geneticists wanted to understand .so Morgan when he got interested in genetics he set out to work on the genetics of coat color in mammals but mammals are expensive.Morgan couldn't actually raise the money to do this work Morgan's inability to get funded to work on coat color in mammals was probably one of the most fortunate grants turndowns in the history of science because it led Morgan by necessity to start working on a different model organism the Fruit fly a small little fly its scientific name is Drosophila Melagoster and commonly known as Drosophila.
As it turns out Drosophila very quickly became and remains to this day the single most important model organism used in both classical and molecular studies of genetics.From Morgan's point of view there are a lot of advantages to working on fruit flies (i) first of all their cheap and (ii)Fruit flies are also very easy to raise in the laboratory . most important in one of the reasons that supplies remain such an important model organism today(iii) they have a very short generation time adult fruit flies will develop from eggs in only a matter of days and what this means is that it's possible to observe the results of genetic crosses in a very short period time you can do a lot of process he didn't have to wait for those garden peas to growup over a matter of months within a few days you know the answer.
There were some serious problems working with fruit flies that fruit flies that you collect from the wild don't have obvious phenotypic variance. if you put out your pineapple and collect fruit flies, to a first approximation they all look the same ,that is the fruit fly didn't offer traits that Morgan could use in particular establish crosses. This seems like the major problem How you going to understand the genetics of trait transmission if there are obvious traits that you can follow in her crosses. but remember that Morgan was interested in mutation so his first goal really when he started working with Drosophila was to see if and how a mutant phenotype might emerge in a natural wild population .
Morgan and his students and the legion of people who followed him studying fruit flies refer to the phenotypes of these fruit flies in particular ways. they referred to the characteristic that you would observe in a wild fruit fly as being the wild type phenotype. because wild fruit flies don't have a lot of visible variation. it means that basically all fruit flies that you collect our basically just composed of wild type phenotype for any particular characteristic you might be interested. now if they observed an unusual phenotype specifically phenotype that they thought was the mutation they call it a mutant phenotype. we have wild type and mutant phenotypes that are what we're really looking at when we look at fruit flies and the assumption here is that the mutant phenotype somehow must be the result of a mutation in allele for the gene responsible for the trait .another detail is that Morgan and the people who have followed up on fruit flies uses slightly different convention for labeling their alleles,the way it is Morgan designated or labeled essentially the kind of mutant alleles and genotypes he was working with was by him labeling the allele according to the phenotypic characteristic of the mutation of the mutant phenotype don't let me make this clear with an example of a well-known mutation in Drosophila which involved a reduction in the size of wings and these guys are just tiny little flies they have wings but one mutation occurs causes those wings do not develop properly that the wings are also small and scrunched up this mutation has been labeled the vestigial wing mutation or just simply vestigial wings we would label the allele responsible for this mutation VG. the interesting thing is that the mutation in are named after the mutant phenotype not the wild type phenotype.the mutant allele would be referred to as VG and the wild type allele for that same gene we would call VG + .
for any particular mutation that Morgan was studying we can safely assume that the typical wild type Drosophila the one that Morgan would just collect out on his pineapple is homozygous for the wild type allele if we were interested in the vestigial wing of trait if we just caught a wild type individual we would assume it's homozygous for VG + VG + that would be a phenotype for that particular trait.
we observe a mutant that mutant must have at least one mutant allele by for example in that case it's got to be at least VG + VG but actually more often than not the mutant alleles that we find in Drosophila are recessive alles. if we find mutation if we find a mutant phenotype of vestigial wing fly then we can be pretty sure that it's homozygous for the recessive mutant allele in other words it would be VG VG a genotype that particular trait.
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.
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 .
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
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.
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.
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.
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.
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.
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.
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
The official name of TSHB gene is thyroid stimulating hormone, beta.The TSHB gene provides instructions for making a protein subunit of a hormone called thyroid stimulating hormone (TSH). Thyroid stimulating hormone consists of two subunits called alpha and beta. The TSHB gene provides instructions for making the beta (B) subunit of thyroid stimulating hormone. The alpha and beta subunits are bound together to produce the active form of the hormone. A particular segment of the beta subunit, known as the buckle or seatbelt, wraps around the alpha subunit to form the functional hormone.
Thyroid stimulating hormone is made in the pituitary gland, a gland at the base of the brain. This hormone plays an important role in the growth and function of the thyroid gland, a butterfly-shaped tissue in the lower neck. It also stimulates the production of thyroid hormones, which play a critical role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). The pituitary gland monitors levels of thyroid hormones. When thyroid hormone levels are too low, the pituitary gland releases thyroid stimulating hormone into the bloodstream. Thyroid stimulating hormone, in turn, signals increased thyroid gland growth and production of thyroid hormones.
Location:
TSHB gene is present in human chromosome 1 and ts coded from region 115373938 to 115378464, the cytogenetic location 1p13
Disease
Researchers have identified several TSHB mutations that alter the size or shape of the thyroid stimulating hormone beta subunit. Many of these mutations affect the beta subunit's seatbelt region, which holds the alpha subunit in place and stabilizes the hormone's structure. Some mutations severely shorten the beta subunit, eliminating the seatbelt region partially or entirely. Other mutations change the chemical building blocks (amino acids) used to make the beta subunit. As a result, the seatbelt region cannot buckle around the alpha subunit. TSHB mutations prevent the production of functional thyroid stimulating hormone or its release (secretion) from the pituitary gland. As a result, thyroid hormone production is not stimulated, leading to low hormone levels that are characteristic of congenital hypothyroidism. Additionally, the thyroid gland is reduced in size (hypoplastic) because its growth is not stimulated.
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
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.
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.
The official name of SDHB gene is succinate dehydrogenase complex, subunit B, iron sulfur (Ip),The SDHB gene provides instructions for making a protein called succinate dehydrogenase(SDH). The succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHB subunit is connected to the SDHA subunit on the hydrophilic, catalytic end of the SDH complex. It is also connected to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane. The subunit is an iron-sulfur protein with three iron-sulfur clusters. It weighs 30 kDa.The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain.
SDHB acts as an intermediate in the basic SDH enzyme action:
1. SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2. 2. Electrons from the FADH2 are transferred to the SDHB subunit iron clusters [2Fe-2S],[4Fe-4S],[3Fe-4S]. 3. Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.This function is part of the Respiratory chain.
Sporadic and familial mutations in this gene result in paragangliomas (glomus tumors)and pheochromocytoma, and support a link between mitochondrial dysfunction and tumorigenesis.
Mutations causing disease have been seen in exons 1 through 7, but not 8. As with the SDHC and SDHD genes, SDHB is a tumor suppressor gene. Note the SDHA gene is not a tumor suppressor gene.
Tumor formation generally follows the Knudson "two hit" hypothesis. The first copy of the gene is mutated in all cells, however the second copy functions normally. When the second copy mutates in a certain cell due to a random event, Loss of Heterozygosity (LOH) occurs and the SDHB protein is no longer produced. Tumor formation then becomes possible.
Given the fundamental nature of the SDH protein in all cellular function, it is not currently understood why only paraganglionic cells are affected. However, the sensitivity of these cells to oxygen levels may play a role.
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.
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.
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.
Northern blot is a technique used in molecular biology research to study gene expression. It takes its name from its similarity to the Southern blot technique, named for biologist Edwin Southern. The major difference is that RNA, rather than DNA, is analyzed in the northern blot. Both techniques use electrophoresis and detection with a hybridization probe. The northern blot technique was developed in 1977 by James Alwine, David Kemp, and George Stark at Stanford University.
A northern blot is very similar to a Southern blot except that it is RNA rather than DNA which is extracted, run on a gel and transferred to a filter membrane. There are 3 types of RNA: tRNA (transfer RNA - active in assembly of polypeptide chains), rRNA (ribosomal RNA - part of the structure of ribosomes) and mRNA (messenger RNA - the product of DNA transcription and used for translation of a gene into a protein). It is mRNA which is isolated and hybridized in northern blots.
mRNA is extracted from the cells grown in galactose and cells grown in glucodse and purified.
The mRNA is loaded onto a gel for electrophoresis. Lane 1 has gal mRNa Lane 2 has the Glucose mRNA.
An electric current is passed through the gel and the RNA moves away from the negative electrode. The distance moved depends on the size of the RNA fragment. Since genes are different sizes the size of the mRNAs varies also. This results in a smear on a gel. Standards are used to quantitate the size. The RNA can be visualized by staining first with a fluorescent dye and then lighting with UV.
RNA is single-stranded, so it can be transferred out of the gel and onto a membrane without any further treatment. The transfer can be done electrically or by capillary action with a high salt solution.
A GAL DNA probe is incubated with the blot.the single stranded GAL DNA probe binds with immobilized GAL mRNA The blot is washed to remove non-specifically bount probe and then a development step allows visualization of the probe that is bound.
The official name of PSEN2 gene is presenilin 2 (Alzheimer disease 4),The PSEN2 gene provides instructions for making a protein called presenilin 2. Presenilin 2 helps process certain proteins that are important for transmitting biochemical signals from the cell membrane into the nucleus of the cell. In the nucleus, these signals turn on (activate) particular genes that are important for cell growth and maturation. Presenilin 2 is also involved in processing amyloid precursor protein, which is found in the brain and other tissues. Research suggests that presenilin 2 works as part of an enzyme complex that cuts amyloid precursor protein into smaller segments (peptides). One of these peptides is called soluble amyloid precursor protein (sAPP) and another is called amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells in both embryonic and adult brain tissue. Other functions of sAPP and amyloid beta peptide are under investigation.
Location: PSEN gene is present in human chromosome 1 and ts coded from region 225124896 to 225150427, the cytogenetic location 1q31-q42
Disorder: Mutations in this gene causes Alzheimer's disease 4
Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 or PSEN2) or the amyloid precursor protein (APP).Researcher have found approxiametly 11 mutaions in PSEN gene have been shown to cause type 4 Alzheimer disease.Two of the most common PSEN2 mutations that cause type 4 Alzheimer disease change one of the building blocks (amino acids) used to make presenilin 2. One mutation replaces the amino acid asparagine with the amino acid isoleucine at position 141 (written as Asn141Ile or N141I). The other mutation changes the amino acid methionine to the amino acid valine at position 239 (written as Met239Val or M239V). These mutations appear to affect the processing of amyloid precursor protein.These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor such that, they either directly regulate gamma-secretase activity, or themselves act are protease enzymes. Two alternatively spliced transcript variants encoding different isoforms of PSEN2 have been identified.
Cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light. Early in the development of age-related cataract the power of the lens may be increased, causing near-sightedness (myopia), and the gradual yellowing and opacification of the lens may reduce the perception of blue colours. Cataracts typically progress slowly to cause vision loss and are potentially blinding if untreated.
Senile cataract, occurring in the aged, is characterized by an initial opacity in the lens, subsequent swelling of the lens and final shrinkage with complete loss of transparency.
Moreover, with time the cataract cortex liquefies to form a milky white fluid in a Morgagnian cataract, which can cause severe inflammation if the lens capsule ruptures and leaks. Untreated, the cataract can cause phacomorphic glaucoma. Very advanced cataracts with weak zonules are liable to dislocation anteriorly or posteriorly. Such spontaneous posterior dislocations (akin to the historical surgical procedure of couching) in ancient times were regarded as a blessing from the heavens, because some perception of light was restored in the cataractous patients.
Causes
Cataracts develop from a variety of reasons, including long-term exposure to ultraviolet light, exposure to radiation, secondary effects of diseases such as diabetes, hypertension and advanced age, or trauma (possibly much earlier); they are usually a result of denaturation of lens protein. Genetic factors are often a cause of congenital cataracts and positive family history may also play a role in predisposing someone to cataracts at an earlier age, a phenomenon of "anticipation" in pre-senile cataracts.
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.
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.
A series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins and other cofactors in order to function properly. Because of the many chemicals that may be involved, pathways can be quite elaborate. In addition, many pathways can exist within a cell.
Organisms contain many different kinds of enzymes that catalyze a variety of different reactions. many of these reactions, such as those involved in the biosynthesis of an amino acid are carried out in a specific sequence called biochemical pathway.
In such pathways, a substrate is converted into a product by te first enzyme in the pathway and the product of the first reaction then becomes the substrate for the next reaction. The sequence of reactions continues until the final product is made.
when a biochemical pathway is functioning, the initial substrate is continually converted to the final product through the series of steps in the pathway
Bupropion is an atypical antidepressant that acts as a norepinephine and dopamine reuptake inhibitor, and nicotinic antagonist ,Initially researched and marketed as an antidepressant, bupropion was subsequently found to be effective as a smoking cessation aid.
Bupropion reduces the severity of nicotine cravings and withdrawal symptoms. After a seven-week treatment, 27% of subjects who received bupropion reported that an urge to smoke was a problem, versus 56% of those who received placebo. In the same study, 21% of the bupropion group reported mood swings, versus 32% of the placebo group. The bupropion treatment course lasts for seven to twelve weeks, with the patient halting the use of tobacco about ten days into the course. The efficacy of bupropion is similar to that of nicotine replacement therapy. Bupropion approximately doubles the chance of quitting smoking successfully after three months. One year after the treatment, the odds of sustaining smoking cessation are still 1.5 times higher in the bupropion group than in the placebo group. The combination of bupropion and nicotine appears not to further increase the cessation rate. In a direct comparison, varenicline (Chantix) showed superior efficacy: after one year, the rate of continuous abstinence was 10% for placebo, 15% for bupropion, and 23% for varenicline. Bupropion slows the weight gain that often occurs in the first weeks after quitting smoking (after seven weeks, the placebo group had an average 2.7 kg increase in weight, versus 1.5 kg for the bupropion group). With time, however, this effect becomes negligible (after 26 weeks, both groups recorded an average 4.8 kg weight gain).
Activity of Bupropionins
Bupropionis may further improve smoking cessation succesfully rate, Nicotine facilitates norpnephron and dopamine release in the central nervous system bupropion mares nicotine by inhibiting norodrenaline and dopamine reuptake a process that some researchers believe alters nicotine withdrawal symptoms. Pulmonary rehabilitation involves education and exercise aimed at improving patient’s quality of life eliminating COPD burden
Prof.Stephen Nowicki professor of Biology in Duke University tells about How Things Get Done in the Cell especially about protein studies,Proteomics is one of the important part in biotechnolgical studies,hop this lecture is useful.
