Cancer-Anti-PlGF inhibitors

The animation tell about,how Anti-PlGF inhibitors can be used prevents the cancerous growth
One of 4 persons will be diagnosed with cancer. In many cases current therapy does not provide an effective cure. Biologists know that normal cells divide in a highly regulated in strictly controlled manner and the cancerous tumors are formed when a cell becomes abnormal and divide without control.
Cells of the immune system are capable of detecting and killing these abnormal cells. But in cases of serious disease the rate of cancer cell divisions surpasses the effect of immune system and tumor continues to grow. In order to acquire the nutrients that necessary for growth tumor cells release of growth factors called PLGF that binds to receptors on nearby capillary blood vessels.

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This causes the capillary network to expand through the tumor provides increased blood supply and simulating tumor growth. Scientists have discovered that the process can be blocked by the administration of a small molecule called Anti-PLGF Antibody; the antibody binds to the PLGF growth factor thereby preventing associated with the Capillary vessels. This effectively blocks the expansion of capillary network and tumor growth is slowed because of limited blood supply. Because of the strong positive effect of Anti-PLGF antibodies the cancer killing cells of the immune system can now work faster than rate of cancer cell divisions
Cells of the immune system are capable of detecting and killing these abnormal cells. But in cases of serious disease the rate of cancer cell divisions surpasses the effect of immune system and tumor continues to grow. In order to acquire the nutrients that necessary for growth tumor cells release of growth factors called PLGF that binds to receptors on nearby capillary blood vessels, this causes the capillary network to expand through the tumor provides increased blood supply and simulating tumor growth. Scientists have discovered that the process can be blocked by the administration of a small molecule called Anti-PLGF Antibody; the antibody binds to the PLGF growth factor thereby preventing associated with the Capillary vessels. This effectively blocks the expansion of capillary network and tumor growth is slowed because of limited blood supply. Because of the strong positive effect of Anti-PLGF antibodies the cancer killing cells of the immune system can now work faster than rate of cancer cell divisions

Cellular Respiration Overview Animation

Cellular respiration is the set of the metabolic reactions and processes that take place in organisms' cells to convert biochemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. The reactions involved in respiration are catabolic reactions that involve the oxidation of one molecule and the reduction of another.
Nutrients commonly used by animal and plant cells in respiration include glucose, amino acids and fatty acids, and a common oxidizing agent (electron acceptor) is molecular oxygen (O2). Bacteria and archaea can also be lithotrophs and these organisms may respire using a broad range of inorganic molecules as electron donors and acceptors, such as sulfur, metal ions, methane or hydrogen. Organisms that use oxygen as a final electron acceptor in respiration are described as aerobic, while those that do not are referred to as anaerobic.

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The energy released in respiration is used to synthesize ATP to store this energy. The energy stored in ATP can then be used to drive processes requiring energy, including biosynthesis, locomotion or transportation of molecules across cell membranes. Because of its ubiquity in nature, ATP is also known as the "universal energy currency".
Aerobic respiration
Aerobic respiration requires oxygen in order to generate energy (ATP). It is the preferred method of pyruvate breakdown from glycolysis and requires that pyruvate enter the mitochondrion in order to be fully oxidized by the Krebs cycle. The product of this process is energy in the form of ATP (Adenosine Triphosphate), by substrate-level phosphorylation, NADH and FADH2.
The reducing potential of NADH and FADH2 is converted to more ATP through an electron transport chain with oxygen as the "terminal electron acceptor". Most of the ATP produced by aerobic cellular respiration is made by oxidative phosphorylation. This works by the energy released in the consumption of pyruvate being used to create a chemiosmotic potential by pumping protons across a membrane. This potential is then used to drive ATP synthase and produce ATP from ADP. Biology textbooks often state that 38 ATP molecules can be made per oxidised glucose molecule during cellular respiration (2 from glycolysis, 2 from the Krebs cycle, and about 34 from the electron transport system).[1] However, this maximum yield is never quite reached due to losses (leaky membranes) as well as the cost of moving pyruvate and ADP into the mitochondrial matrix and current estimates range around 29 to 30 ATP per glucose.

Aerobic metabolism is 19 times more efficient than anaerobic metabolism (which yields 2 mol ATP per 1 mol glucose). They share the initial pathway of glycolysis but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. The post glycolytic reactions take place in the mitochondria in eukaryotic cells, and in the cytoplasm in prokaryotic cells.
Glycolysis is a metabolic pathway that is found in the cytoplasm of cells in all living organisms and is anaerobic, or doesn't require oxygen. The process converts one molecule of glucose into two molecules of pyruvate, and makes energy in the form of two net molecules of ATP. Four molecules of ATP per glucose are actually produced; however, two are consumed for the preparatory phase. The initial phosphorylation of glucose is required to destabilize the molecule for cleavage into two triose sugars. During the pay-off phase of glycolysis, four phosphate groups are transferred to ADP by substrate-level phosphorylation to make four ATP, and two NADH are produced when the triose sugars are oxidized.
Oxidative decarboxylation of pyruvate
The pyruvate is oxidized to acetyl-CoA and CO2 by the Pyruvate dehydrogenase complex, a cluster of enzymes—multiple copies of each of three enzymes—located in the mitochondria of eukaryotic cells and in the cytosol of prokaryotes. In the process one molecule of NADH is formed per pyruvate oxidized, and 3 moles of ATP are formed for each mole of pyruvate. This step is also known as the link reaction, as it links glycolysis and the Krebs cycle.
Citric acid cycle
This is also called the Krebs cycle or the tricarboxylic acid cycle. When oxygen is present, acetyl-CoA is produced from the pyruvate molecules created from glycolysis. Once Acetyl CoA is formed, two processes can occur, aerobic or anaerobic respiration. When oxygen is present, the mitochondria will undergo aerobic respiration which leads to the Krebs cycle. However, if oxygen is not present, fermentation of the pyruvate molecule will occur. In the presence of oxygen, when acetyl-CoA is produced, the molecule then enters the citric acid cycle (Krebs cycle) inside the mitochondrial matrix, and gets oxidized to CO2 while at the same time reducing NAD to NADH. NADH can be used by the electron transport chain to create further ATP as part of oxidative phosphorylation. To fully oxidize the equivalent of one glucose molecule, two acetyl-CoA must be metabolized by the Krebs cycle. Two waste products, H2O and CO2, are created during this cycle.
The citric acid cycle is an 8-step process involving 8 different enzymes. Throughout the entire cycle, Acetyl CoA changes into Citrate, Isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, and finally, oxaloacetate. The net energy gain from one cycle is 3 NADH, 1 FADH, and 1 ATP. Thus, the total amount of energy yield from one whole glucose molecule (2 pyruvate molecules) is 6 NADH, 2 FADH, and 2 ATP.
Oxidative phosphorylation
In eukaryotes, oxidative phosphorylation occurs in the mitochondrial cristae. It comprises the electron transport chain that establishes a proton gradient (chemiosmotic potential) across the inner membrane by oxidizing the NADH produced from the Krebs cycle. ATP is synthesised by the ATP synthase enzyme when the chemiosmotic gradient is used to drive the phosphorylation of ADP. The electrons are finally transferred to exogenous oxygen, and with the addition of two protons, water is formed.


ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. The ELISA has been used as a diagnostic tool in medicine and plant pathology, as well as a quality control check in various industries. In simple terms, in ELISA an unknown amount of antigen is affixed to a surface, and then a specific antibody is washed over the surface so that it can bind to the antigen. This antibody is linked to an enzyme, and in the final step a substance is added that the enzyme can convert to some detectable signal. Thus in the case of fluorescence ELISA, when light of the appropriate wavelength is shone upon the sample, any antigen/antibody complexes will fluoresce so that the amount of antigen in the sample can be inferred through the magnitude of the fluorescence.
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Performing an ELISA involves at least one antibody with specificity for a particular antigen. The sample with an unknown amount of antigen is immobilized on a solid support (usually a polystyrene microtiter plate) either non-specifically (via adsorption to the surface) or specifically (via capture by another antibody specific to the same antigen, in a "sandwich" ELISA). After the antigen is immobilized the detection antibody is added, forming a complex with the antigen. The detection antibody can be covalently linked to an enzyme, or can itself be detected by a secondary antibody which is linked to an enzyme through bioconjugation. Between each step the plate is typically washed with a mild detergent solution to remove any proteins or antibodies that are not specifically bound. After the final wash step the plate is developed by adding an enzymatic substrate to produce a visible signal, which indicates the quantity of antigen in the sample. Older ELISAs utilize chromogenic substrates, though newer assays employ fluorogenic substrates enabling much higher sensitivity.
The ELISA test, or the enzyme immunoassay (EIA), was the first screening test commonly employed for HIV. It has a high sensitivity. In an ELISA test, a person's serum is diluted 400-fold and applied to a plate to which HIV antigens have been attached. If antibodies to HIV are present in the serum, they may bind to these HIV antigens. The plate is then washed to remove all other components of the serum. A specially prepared "secondary antibody" — an antibody that binds to other antibodies — is then applied to the plate, followed by another wash. This secondary antibody is chemically linked in advance to an enzyme. Thus the plate will contain enzyme in proportion to the amount of secondary antibody bound to the plate. A substrate for the enzyme is applied, and catalysis by the enzyme leads to a change in color or fluorescence. ELISA results are reported as a number; the most controversial aspect of this test is determining the "cut-off" point between a positive and negative result.
ELISA Demonstration Bookmark and Share  Subscribe in a reader Types The steps of the general, "indirect," ELISA for determining serum antibody concentrations are:
  • Apply a sample of known antigen of known concentration to a surface, often the well of a microtiter plate. The antigen is fixed to the surface to render it immobile. Simple adsorption of the protein to the plastic surface is usually sufficient. These samples of known antigen concentrations will constitute a standard curve used to calculate antigen concentrations of unknown samples. Note that the antigen itself may be an antibody.
  • A concentrated solution of non-interacting protein, such as bovine serum albumin (BSA) or casein, is added to all plate wells. This step is known as blocking, because the serum proteins block non-specific adsorption of other proteins to the plate.
  • The plate wells or other surface are then coated with serum samples of unknown antigen concentration, diluted into the same buffer used for the antigen standards. Since antigen immobilization in this step is due to non-specific adsorption, it is important for the total protein concentration to be similar to that of the antigen standards.
  • The plate is washed, and a detection antibody specific to the antigen of interest is applied to all plate wells. This antibody will only bind to immobilized antigen on the well surface, not to other serum proteins or the blocking proteins.
  • Secondary antibodies, which will bind to any remaining detection antibodies, are added to the wells. These secondary antibodies are conjugated to the substrate-specific enzyme. This step may be skipped if the detection antibody is conjugated to an enzyme.
  • Wash the plate, so that excess unbound enzyme-antibody conjugates are removed.
  • Apply a substrate which is converted by the enzyme to elicit a chromogenic or fluorogenic or electrochemical signal.
  • View/quantify the result using a spectrophotometer, spectrofluorometer, or other optical/electrochemical device.
Sandwich ELISA A less-common variant of this technique, called "sandwich" ELISA, is used to detect sample antigen. The steps are as follows:
  • Prepare a surface to which a known quantity of capture antibody is bound.
  • Block any non specific binding sites on the surface.
  • Apply the antigen-containing sample to the plate.
  • Wash the plate, so that unbound antigen is removed.
  • Apply primary antibodies that bind specifically to the antigen.
  • Apply enzyme-linked secondary antibodies which are specific to the primary antibodies.
  • Wash the plate, so that the unbound antibody-enzyme conjugates are removed.
  • Apply a chemical which is converted by the enzyme into a color or fluorescent or electrochemical signal.
  • Measure the absorbance or fluorescence or electrochemical signal (e.g., current) of the plate wells to determine the presence and quantity of antigen.
Competitive ELISA A third use of ELISA is through competitive binding. The steps for this ELISA are somewhat different than the first two examples:
  • Unlabeled antibody is incubated in the presence of its antigen.
  • These bound antibody/antigen complexes are then added to an antigen coated well.
  • The plate is washed, so that unbound antibody is removed. (The more antigen in the sample, the less antibody will be able to bind to the antigen in the well, hence "competition.")
  • The secondary antibody, specific to the primary antibody is added. This second antibody is coupled to the enzyme.
  • A substrate is added, and remaining enzymes elicit a chromogenic or fluorescent signal.
For competitive ELISA, the higher the original antigen concentration, the weaker the eventual signal.
(Note that some competitive ELISA kits include enzyme-linked antigen rather than enzyme-linked antibody. The labeled antigen competes for primary antibody binding sites with your sample antigen (unlabeled). The more antigen in the sample, the less labeled antigen is retained in the well and the weaker the signal).
ELISA Reverse method & device (ELISA-R m&d)
A newer technique uses a solid phase made up of an immunosorbent polystyrene rod with 4-12 protruding ogives. The entire device is immersed in a test tube containing the collected sample and the following steps (washing, incubation in conjugate and incubation in chromogenous) are carried out by dipping the ogives in microwells of standard microplates pre-filled with reagents.
  • The ogives can each be sensitized to a different reagent, allowing the simultaneous detection of different antibodies and different antigens for multi-target assays;
  • The sample volume can be increased to improve the test sensitivity in clinical (saliva, urine), food (bulk milk, pooled eggs) and environmental (water) samples;
  • One ogive is left unsensitized to measure the non-specific reactions of the sample;
  • The use of laboratory supplies for dispensing sample aliquots, washing solution and reagents in microwells is not required, facilitating ready-to-use lab-kits and on-site kits.

Apoptosis & Caspase 8 - PMAP

Caspases, or cysteine-aspartic acid proteases, are a family of cysteine proteases, which play essential roles in apoptosis (programmed cell death), necrosis and inflammation.
Caspases are essential in cells for apoptosis, one of the main types of programmed cell death in development and most other stages of adult life, and have been termed "executioner" proteins for their roles in the cell. Some caspases are also required in the immune system for the maturation of cytokines. Failure of apoptosis is one of the main contributions to tumour development and autoimmune diseases; this coupled with the unwanted apoptosis that occurs with ischemia or Alzheimer's disease, has boomed the interest in caspases as potential therapeutic targets since they were discovered in the mid 1990s.

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Caspase 8 is a caspase protein. It most likely acts upon caspase 3.This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined.

Protease-activated receptor

Protease-activated receptors are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets, but also on endothelial cells, myocytes and neurons.
There are 4 known protease-activated receptors or PAR's, numbered from one to four. These receptors are members of the seven transmembrane G-protein-coupled receptor superfamily, and are expressed throughout the body.

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Classification Activation
PAR's are activated by the action of serine proteases such as thrombin (acts on PAR's 1, 3 and 4) and trypsin (PAR 2). These enzymes cleave the N-terminus of the receptor, which in turn acts as a tethered ligand. In the cleaved state, part of the receptor itself acts as the agonist, causing a physiological response.
Most of the PAR family act through the actions of G-proteins i (cAMP inhibitory), 12/13 (Raf/Ras activation) and q (calcium signalling) to cause cellular actions.
Recent research has implicated these novel receptors in the inflammatory response (including arthritis), muscle growth, and bone cell differentiation and proliferation.

Laminectomy animation

Laminectomy is a spine operation to remove the portion of the vertebral bone called the lamina. There are many variations of laminectomy, in the most minimal form small skin incisions are made, back muscles are pushed aside rather than cut, and the parts of the vertebra adjacent to the lamina are left intact. The traditional form of laminectomy (conventional laminectomy) excises much more than just the lamina, the entire posterior backbone is removed, along with overlying ligaments and muscles. The usual recovery period is very different depending on which type of laminectomy has been performed: days in the minimal procedure, and weeks to months with conventional open surgery.

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the lamina is a posterior arch of the vertebral bone laying between the spinous process, which juts out in the midline, and the more lateral of each vertebra. The pair of lamina, along with the spinous process, make up the posterior wall of the bony spinal canal. Although the literal meaning of laminectomy is excision of the lamina, the operation called conventional laminectomy, which is a standard spine procedure in neurosurgery and orthopedics, removes the lamina, spinous process and overlying connective tissues and ligaments, cutting through the muscles that overlie these structures. Minimal surgery laminectomy is a tissue preserving surgery that leaves the muscles intact, spares the spinal process and takes only one or both lamina. Laminotomy is removal of a mid-portion of one lamina and may be done either with a conventional open technique, or in a minimal fashion with the use of tubular retractors and endoscopes.
A lamina is rarely, if ever, removed because it itself is diseased. Instead, removal is done to: (1) break the continuity of the rigid ring of the spinal canal to allow the soft tissues within the canal to expand (decompression), or (2) as one step in changing the contour of the vertebral column, or (3) in order to allow the surgeon access to deeper tissues inside the spinal canal. Laminectomy is also the name of a spinal operation that conventionally includes the removal of one or both lamina as well as other posterior supporting structures of the vertebral column, including ligaments and additional bone.
Conventional open laminectomy often involves excision of the posterior spinal ligament, and some or all of the spinous process, and facet joint. Removal of these structures, in the open technique, requires cutting the many muscles of the back which attach to them. Laminectomy performed as a minimal spinal surgery procedure, however, allows the bellies of muscles to be pushed aside instead of transected, and generally involves less bone removal than the open procedure.
The success rate of laminectomy depends on the specific reason for the operation, as well as proper patient selection and technical ability of the surgeon. Indications for laminectomy include (1) treatment of severe spinal stenosis by relieving pressure on the spinal cord or nerve roots, (2) access to a tumor or other mass lying in or around the spinal cord, or (3) a step in tailoring the contour of the vertebral column to correct a spinal deformity such as kyphosis. The actual bone removal may be carried out with a variety of surgical tools, including drills, rongeurs, and laser.
The recovery period after laminectomy depends on the specific operative technique; minimally invasive procedures having a significantly shorter recovery period than open surgery. Removal of substantial amounts of bone and tissue may require additional procedures to stabilize the spine, such as fusion procedures, and spinal fusion generally requires a much longer recovery period than simple laminectomy.

Hypertension in Pregnant Women

Although many pregnant women with high blood pressure have healthy babies without serious problems, high blood pressure can be dangerous for both the mother and the fetus. Women with pre-existing, or chronic, high blood pressure are more likely to have certain complications during pregnancy than those with normal blood pressure. However, some women develop high blood pressure while they are pregnant (often called gestational hypertension).

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The effects of high blood pressure range from mild to severe. High blood pressure can harm the mother's kidneys and other organs, and it can cause low birth weight and early delivery. In the most serious cases, the mother develops preeclampsia--or "toxemia of pregnancy"--which can threaten the lives of both the mother and the fetus.

Preeclampsia is a condition that typically starts after the 20th week of pregnancy and is related to increased blood pressure and protein in the mother's urine (as a result of kidney problems). Preeclampsia affects the placenta, and it can affect the mother's kidney, liver, and brain. When preeclampsia causes seizures, the condition is known as eclampsia--the second leading cause of maternal death in the U.S. Preeclampsia is also a leading cause of fetal complications, which include low birth weight, premature birth, and stillbirth.

There is no proven way to prevent preeclampsia. Most women who develop signs of preeclampsia, however, are closely monitored to lessen or avoid related problems. The only way to "cure" preeclampsia is to deliver the baby.

Circulatory Changes at Birth

Development of the cardiovascular system - … Begins to develop toward the end of the third week … Heart starts to beat at the beginning of the fourth week … The critical period of heart development is from day 20 to day 50 after fertilization. … Many critical events occur during cardiac development, and any deviation from this normal pattern can cause congenital heart defects, if development of heart doesnít occur properly. … However, we will concern ourselves with the events surrounding the circulatory changes at birth. Trace path of blood in diagram of fetal circulation (see diagram) Three shunts in the fetal circulation  1. Ductus arteriosus … protects lungs against circulatory overload … allows the right ventricle to strengthen … hi pulmonary vascular resistance, low pulmonary blood flow … carries mostly med oxygen saturated blood 2. Ductus venosus … fetal blood vessel connecting the umbilical vein to the IVC … blood flow regulated via sphincter … carries mostly hi oxygenated blood 3. Foramen ovale … shunts highly oxygenated blood from right atrium to left atrium.

DNA Damage and Protection Video

Lipoprotein Video

Lipoprotein is a biochemical assembly that contains both proteins and lipids. The lipids or their derivatives may be covalently or non-covalently bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins and toxins are lipoproteins. Examples include the high density and low density lipoproteins which enable fats to be carried in the blood stream, the transmembrane proteins of the mitochondrion and the chloroplast, and bacterial lipoproteins

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The function of lipoprotein particles is to transport lipids (fats) around the body in the aqueous blood, in which they would not normally dissolve.
All cells use and rely on fats and, for all animal cells, cholesterol as building blocks to create the multiple membranes which cells use to both control internal water content, internal water soluble elements and to organize their internal structure and protein enzymatic systems.
The protein particles have hydrophilic groups aimed outward so as to attract water molecules; this makes them soluble in the salt water based blood pool. Triglyceride-fats and cholesterol are carried internally, shielded from the water by the protein particle.
The interaction of the proteins forming the surface of the particles with (a) enzymes in the blood, (b) with each other and (c) with specific proteins on the surfaces of cells, determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.
Regarding atheroma development and progression vs. regression, the key issue has always been cholesterol transport patterns, not cholesterol concentration itself.
Transmembrane lipoproteins
The lipids are often an essential part of the complex, even if they seem to have no catalytic activity themselves. To isolate transmembrane lipoproteins from their associated membranes, detergents are often needed.
The handling of lipoproteins in the body is referred to as lipoprotein metabolism. It is divided into two pathways, exogenous and endogenous, depending in large part on whether the lipoproteins in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous).
Exogenous pathway
Epithelial cells lining the small intestine readily absorb lipids from the diet. These lipids, including triglycerides, phospholipids, and cholesterol, are assembled with apolipoprotein B-48 into chylomicrons. These nascent chylomicrons are secreted from the intestinal epithelial cells into the lymphatic circulation in a process that depends heavily on apolipoprotein B-48. As they circulate through the lymphatic vessels, nascent chylomicrons bypass the liver circulation and are drained via the thoracic duct into the bloodstream.
In the bloodstream, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent chylomicron; the chylomicron is now considered mature. Via apolipoprotein C-II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes a hydrolysis reaction that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can be absorbed in peripheral tissues, especially adipose and muscle, for energy and storage.
The hydrolyzed chylomicrons are now considered chylomicron remnants. The chylomicron remnants continue circulating until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.
Endogenous pathway
The liver is another important source of lipoproteins, principally VLDL. Triacylglycerol and cholesterol are assembled with apolipoprotein B-100 to form VLDL particles. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100.
As in chylomicron metabolism, the apolipoprotein C-II and apolipoprotein E of VLDL particles are acquired from HDL particles. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature.
Again like chylomicrons, VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase.
Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called low density lipoproteins (LDL), which contain a relatively high cholesterol content. LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 or E on the LDL particle. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.
Lipoprotein. (2008, December 14). In Wikipedia, The Free Encyclopedia. from

Cancer Stem cells Video

Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. These cells are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors.

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Existing cancer treatments were mostly developed on animal models, where therapies able to promote tumor shrinkage were deemed effective. However, animals could not provide a complete model of human disease. In particular, in mice, whose life spans do not exceed two years, tumor relapse is exceptionally difficult to study.

The efficacy of cancer treatments are, in the initial stages of testing, often measured by the amount of tumor mass they kill off. As CSCs would form a very small proportion of the tumor, this may not necessarily select for drugs that act specifically on the stem cells. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate new cells. A population of CSCs, which gave rise to it, could remain untouched and cause a relapse of the disease.

Importance of stem cells

Not only is finding the source of cancer cells necessary for successful treatments, but if current treatments of cancer do not properly destroy enough CSCs, the tumor will reappear. Including the possibility that the treatment of for instance, chemotherapy, will leave only chemotherapy-resistant CSCs, then the ensuing tumor will most likely also be resistant to chemotherapy. If the cancer tumor is detected early enough, enough of the tumor can be killed off and marginalized with traditional treatment. But as the tumor size increases, it becomes more and more difficult to remove the tumor without conferring resistance and leaving enough behind for the tumor to reappear.

Some treatments with chemotherapy, such as paclitaxel in ovarian cancer (a cancer usually discovered in late stages), may actually serve to promote certain cancer growth (55-75% relapse <2>

This is still an area of ongoing research. Logically, the smallest change (and hence the most likely mutation) to produce a cancer stem cell would be a mutation from a normal stem cell. Also, in tissues with a high rate of cell turnover (such as the skin or GI epithelium, where cancers are common), it can be argued that stem cells are the only cells that live long enough to acquire enough genetic abnormalities to become cancerous. However it is still possible that more differentiated cancer cells (in which the genome is less stable) could acquire properties of 'stemness'.

It is likely that in a tumor there are several lines of stem cells, with new ones being created and others dying off as a tumor grows and adapts to its surroundings. Hence, tumor stem cells can constitute a 'moving target', making them even harder to treat.

Implications for cancer treatment

The existence of CSCs have several implications in terms of future cancer treatment and therapies. These include disease identification, selective drug targets, prevention of metastasis, and development of new strategies in fighting cancer.

Normal somatic stem cells are naturally resistant to chemotherapeutic agents - they have various pumps (such as MDR) that pump out drugs, DNA repair proteins and they also have a slow rate of cell turnover (chemotherapeutic agents naturally target rapidly replicating cells). CSCs, if they are the mutated counterparts of normal stem cells, may also have similar functions which allows them to survive therapy. These surviving CSCs then repopulate the tumor, causing relapse. By selectively targeting CSCs, it would be possible to treat patients with aggressive, non-resectable tumors, as well as preventing the tumor from metastasizing. The hypothesis implies that if the CSCs are eliminated, the cancer would simply regress due to differentiation and cell death.

There has also been a lot of research into finding specific markers that may distinguish CSCs from the bulk of the tumor (as well as from normal stem cells), with some success.Proteomic and genomic signatures of tumors are also being investigated. Success in these area would enable faster identification of tumor subtypes as well as personalized medicine in cancer treatments by using the right combination of drugs and/or treatments to efficiently eliminate the tumor.

Cancer stem cell pathways
A normal stem cell may be transformed into a cancer stem cell through disregulation of the proliferation and differentiation pathways controlling it. Scientists working on CSCs hope to design new drugs targeting these cellular mechanisms. The first findings in this area were made using haematopoietic stem cells (HSCs) and their transformed counterparts in leukemia, the disease whose stem cell origin is most strongly established. However, these pathways appear to be shared by stem cells of all organs.


The Polycomb group transcriptional repressor Bmi-1 was discovered as a common oncogene activated in lymphoma and later shown to specifically regulate HSCs.The role of Bmi-1 has also been illustrated in neural stem cells. The pathway appears to be active in CSCs of pediatric brain tumors.


The Notch pathway has been known to developmental biologists for decades. Its role in control of stem cell proliferation has now been demonstrated for several cell types including haematopoietic, neural and mammary stem cells. Components of the Notch pathway have been proposed to act as oncogenes in mammary and other tumors.

Sonic hedgehog and Wnt

These developmental pathways are also strongly implicated as stem cell regulators. Both Sonic hedgehog(SHH) and Wnt pathways are commonly hyperactivated in tumors and are required to sustain tumor growth. However, the Gli transcription factors that are regulated by SHH take their name from gliomas, where they are commonly expressed at high levels. A degree of crosstalk exists between the two pathways and their activation commonly goes hand-in-hand. This is a trend rather than a rule. For instance, in colon cancer hedgehog signalling appears to antagonise Wnt.

Sonic hedgehog blockers are available, such as cyclopamine. There is also a new water soluble cyclopamine that may be more effective in cancer treatment. There is also DMAPT, a water soluble derivative of parthenolide that targets AML (leukemia) stem cells, and possibly other CSCs as in myeloma or prostate cancer. A clinical trial of DMAPT is to start in England in late 2007 or 2008. Furthermore, GRN163L was recently started in trials to target myeloma stem cells. If it is possible to eliminate the cancer stem cell, than a potential cure may be achieved if there are no more CSCs to repopulate a cancer.

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A New Approach to NMR-Based Protein Structure

The video, created in collaboration with Dr. Michael E. Johnson, Director of the Center for Biotechnology at the University of Illinois, Chicago, introduces a new software approach to NMR-Based protein structure determination developed at the Center for Biotechnology's Bimolecular Analysis Laboratory. The program's developers are introduced and each demonstrated the functionality and advances of the new software. The developers include; Dr. Simon Sherman, a mathematical physicist who developed the basic algorithms, Dr. Leela Kar, an NMR spectroscopist who developed the applications, and Alan Verlo, a computer visualization specialist who developed the program's visualizations.

The video introduces the new program and shows the program's functionality, it's visualizations, and explains the medical and potentially therapeutic benefits to the use of this technology.

Lower Gastrointestinal Endoscopy Animation

Sigmoidoscopy is the minimally invasive medical examination of the large intestine from the rectum through the last part of the colon. There are two types of sigmoidoscopy, flexible sigmoidoscopy, which uses a flexible endoscope, and rigid sigmoidoscopy, which uses a rigid device. Flexible sigmoidoscopy is generally the preferred procedure. A sigmoidoscopy is a very effective screening tool. A sigmoidoscopy is similar but not the same as a colonoscopy. A Sigmoidoscopy only examines up to the sigmoid, the most distal part of the colon, while colonoscopy examines the whole large bowel.

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Flexible sigmoidoscopy enables the physician to look at the inside of the large intestine from the rectum through the last part of the colon, called the sigmoid or descending colon. Physicians may use the procedure to find the cause of diarrhea, abdominal pain, or constipation. They also use it to look for benign and malignant polyps, as well as early signs of cancer in the descending colon and rectum. With flexible sigmoidoscopy, the physician can see intestinal bleeding, inflammation, abnormal growths, and ulcers in the descending colon and rectum. Flexible sigmoidoscopy is not sufficient to detect polyps or cancer in the ascending or transverse colon (two-thirds of the colon). However, although in absolute terms only a relatively small section of the large intestine can be examined using sigmoidoscopy, the sites which can be observed represent areas which are affected by diseases such as colorectal cancer most regularly, eg. the rectum.

For the procedure, the patient must lie on his or her left side on the examining table. The physician inserts a short, flexible, lit tube into the rectum and slowly guides it into the colon. The tube is called a sigmoidoscope. The scope transmits an image of the inside of the rectum and colon, so the physician can carefully examine the lining of these organs. The scope also blows air into these organs, which inflates them and helps the physician see better.

If anything unusual is in the rectum or colon, like a polyp or inflamed tissue, the physician can remove a piece of it using instruments inserted into the scope. The physician will send that piece of tissue (biopsy) to the lab for testing.

Bleeding and puncture of the colon are possible complications of sigmoidoscopy. However, such complications are uncommon.

Flexible sigmoidoscopy takes 10 to 20 minutes. During the procedure, the patient might feel pressure and slight cramping in the lower abdomen, but he or she will feel better afterward when the air leaves the colon.

From Egg to Adult and back Again: Cloning ,stem cells,and cell Replacement

Lecture is presented by Sir John Bertrand Gurdon ,In 1962, Gurdon, then at Oxford University, announced that he had used the nucleus of fully differentiated adult intestinal cells to clone South African clawed frogs (Xenopus laevis).This was the first demonstration in animals that the nucleus of a differentiated somatic cell retains the potential to develop into all cell types (ie, is totipotent) and paved the way for future somatic cell nuclear transfer experiments, including the 1996 cloning of the sheep, Dolly.

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Gurdon began cloning experiments using nonembryonic cells—specifically, cells from the intestinal lining of tadpoles. Gurdon believed that the tadpoles were old enough so that cells taken from them would be differentiated. Gurdon exposed a frog egg to ultraviolet light, which destroyed its nucleus. He then removed the nucleus from the tadpole intestinal cell and implanted it in the enucleated egg. The egg grew into a tadpole that was genetically identical to the DNA-donating tadpole. But the tadpoles cloned in Gurdon’s early experiments never survived to adulthood and scientists now believe that many of the cells used in these experiments may not have been differentiated cells after all. In later work, however, Gurdon successfully produced sexually mature adult frogs from eggs into which genetically marked nuclei had been transplanted from differentiated tadpole cells.

Gurdon’s experiments captured the attention of the scientific community and the tools and techniques he developed for nuclear transfer are still used today. The term clone (from the Greek word klōn, meaning “twig”) had already been in use since the beginning of the 20th century in reference to plants. In 1963 the British biologist J. B. S. Haldane, in describing Gurdon’s results, became one of the first to use the word clone in reference to animals.

Recent research

Gurdon's recent research has focused on analyzing inter cellular signal ling factors involved in cell differentiation, and on elucidating the mechanisms involved in reprogramming the nucleus in transplantation experiments, including demethylation of the transplanted DNA.

Honours and awards

Gurdon was made a Fellow of the Royal Society in 1971, and was knighted in 1995. In 2004, Wellcome/CR UK Institute for Cell Biology and Cancer was renamed the Gurdon Institute in his honour. He has also received numerous awards(Wolf Prize in Medicine (1989), medals and honorary degrees.

Chlamydomonas Video

Chlamydomonas is a motile single celled green alga about 10 micrometres in diameter that swims with two flagella. The species has been spelled several different ways because of different transliterations of the name from Russian: reinhardi, reinhardii and reinhardtii all refer to the same species, C. reinhardtii Dangeard.

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These algae are commonly found in soil and fresh water. They have a cell wall made of hydroxyproline-rich glycoproteins, a large cup-shaped chloroplast, a large pyrenoid, and an "eyespot" that senses light. Normal Chlamydomonas can grow on a simple medium of inorganic salts in the light, using photosynthesis to provide energy. They can also grow in total darkness using acetate as a carbon source for catabolism.

Model organism
Chlamydomonas is used as a model organism for research on fundamental questions in cell and molecular biology such as:

* How do cells move?
* How do cells respond to light?
* How do cells recognize one another?
* How do cells regulate their proteome to control flagellar length?
* How do cells respond to changes in mineral nutrition? (nitrogen, sulfur etc.)

There are many known mutants of C. reinhardtii. These mutants are useful tools for studying a variety of biological processes, including flagellar motility, photosynthesis or protein synthesis. Since Chlamydomonas species are normally haploid, the effects of mutations are seen immediately without further crosses.

In 2007, the complete nuclear genome sequence of C. reinhardtii was published.

Channelrhodopsin-2, a protein that functions as a light-gated cation channel, was originally isolated from C. reinhardtii.

Vegetative cells of the reinhardtii species are haploid with 17 small chromosomes. Under nitrogen starvation, haploid gametes develop. There are two mating types, identical in appearance and known as mt(+) and mt(-), which can fuse to form a diploid zygote. The zygote is not flagellated, and it serves as a dormant form of the species in the soil. In the light the zygote undergoes meiosis and releases four flagellated haploid cells that resume the vegetative life cycle.

Under ideal growth conditions, cells may sometimes undergo two or three rounds of mitosis before the daughter cells are released from the old cell wall into the medium. Thus, a single growth step may result in 4 or 8 daughter cells per mother cell.

The cell cycle of this unicellular green algae can be synchronized by alternating periods of light and dark. The growth phase is dependent on light, whereas, after a point designated as the transition or commitment point, processes are light-independent.

The attractiveness of the alga as a model organism has recently increased with the release of several genomic resources to the public domain. The current draft (Chlre3) of the Chlamydomonas nuclear genome sequence prepared by Joint Genome Institute of the U.S. Dept of Energy comprises 1557 scaffolds totaling 120 Mb. Roughly half of the genome is contained in 24 scaffolds all at least 1.6 Mb in length. The current assembly of the nuclear genome is available online at.

The ~15.8 Kb mitochondrial genome (database accession: NC_ 001638) is available online at the NCBI database. The complete >200 Kb chloroplast genome is available online.

In addition to genomic sequence data there is a large supply of expression sequence data available as cDNA libraries and expressed sequence tags (ESTs). Seven cDNA libraries are available online. A BAC library can be purchased from the Clemson University Genomics Institute . There are also two databases of >50 000 and >160 000 ESTs available online.

Chlamydomonas has been used to study different aspects of evolutionary biology and ecology. It is an organism of choice for many selection experiments because (1) it has a short generation time, (2) it is both a heterotroph and facultative autotroph, (3) it can reproduce both sexually and asexually, and (4) there is a wealth of genetic information already available.

Some examples (non exhaustive) of evolutionary work done with Chlamydomonas include the evolution of sexual reproduction, , the fitness effect of mutations , and the effect of adaptation to different levels of CO2.

DNA transformation techniques
Gene transformation occurs mainly by homologous recombination in the chloroplast and heterologous recombination in the nucleus. The C. reinhardtii chloroplast genome can be transformed using microprojectile particle bombardment and the nuclear genome has been transformed with both glass bead agitation and electroporation. The biolistic procedure appears to be the most efficient way of introducing DNA into the chloroplast genome. This is probably because the chloroplast occupies over half of the volume of the cell providing the microprojectile with a large target. Electroporation has been shown to be the most efficient way of introducing DNA into the nuclear genome with maximum transformation frequencies two orders of magnitude higher than obtained using glass bead method.

"Chlamydomonas reinhardtii." Wikipedia, The Free Encyclopedia. 17 Dec 2008, 01:31 UTC. 5 Jan 2009 .

Paclitaxel molecule Animation

Paclitaxel is a drug used in the treatment of cancer. It was discovered at Research Triangle Institute (RTI) in 1967 when Monroe E. Wall and Mansukh C. Wani isolated the compound from the bark of the Pacific yew tree, Taxus brevifolia, and noted its antitumor activity in a broad range of rodent tumors. By 1970, the two scientists had determined the structure of paclitaxel. Paclitaxel has since become an effective tool of doctors who treat patients with lung, ovarian, breast cancer, and advanced forms of Kaposi's sarcoma. It is sold under the tradename Taxol. Together with docetaxel, it forms the drug category of the taxanes.

Paramecium video

Paramecia are a group of unicellular ciliate protozoa, which are commonly studied as a representative of the ciliate group, and range from about 50 to 350 μm in length, Simple cilia cover the body, which allow the cell to move with a synchronous motion (like a caterpillar). There is also a deep oral groove containing inconspicuous compound oral cilia (as found in other peniculids) used to draw food inside. They generally feed on bacteria and other small cells. Osmoregulation is carried out by a pair of contractile vacuoles, which actively expel water absorbed by osmosis from their surroundings.

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Paramecia are widespread in freshwater environments, and are especially common in scums. Paramecia are attracted by acidic conditions. Certain single-celled eukaryotes, such as Paramecium, are examples for exceptions to the universality of the genetic code (translation systems where a few codons differ from the standard ones).

The paramecium approximates a prolate spheroid, rounded at the front and pointed at the back. The pellicle is a stiff but elastic membrane that gives the paramecium its definite shape. Covering the pellicle are many tiny hairs, called cilia. On the side beginning near the front end continuing down half way is the oral groove, which collects food until it is swept into the cell mouth. There is an opening near the back end called the anal pore. The contractile vacuole and its radiating canals — referred to previously for osmoregulation of the organism, are also found on the outside of a paramecium.

The paramecium contains cytoplasm, trichocysts (“thread capsules”), the gullet, food vacuoles, the macronucleus, and the micronucleus.

For the paramecium to move forward, its cilia beat on an angle, backward. This means that the paramecium moves by spiralling through the water on an invisible axis. For the paramecium to move backward, the cilia simply beat forward on an angle.
If the paramecium runs into a solid object, the cilia changes its direction and beats forward, causing the paramecium to go backward. The paramecium turns slightly and goes forward again. If it runs into the solid object again it will repeat this process until it can get past the object.

Gathering food
Paramecia feed on microorganisms like bacteria, algae, and yeasts. To gather its food, the paramecium uses its cilia to sweep the food along with some water into the cell mouth after it falls into the oral groove. The food goes through the cell mouth into the gullet, which is like the stomach. When enough food has accumulated at the gullet base, it navigates there to form a food vacuole in the cytoplasm, and travels through the cell, through the back end first. As it moves along, enzymes from the cytoplasm enter the vacuole to digest the contents, digested nutrients then going into the cytoplasm, and the vacuole shrinks. When the vacuole reaches the anal pore, it ruptures, expelling its waste contents to the exterior.

One of the most interesting known symbiotic relationships is that of Paramecium aurelia and its bacterial endosymbionts. The bacteria infect the protozoa, and they produce toxic particles that kill sensitive strains, but not killer strains. See also the Chlorella symbiosis with Paramecium bursaria.

Giant amoebas, for instance, have types of endosymbiotes, which seem to function as mitochondria in these amoebas. Another example involves protozoa bacteria that produce cellulases to assist the host protozoan with cellulose digestion (similar to those found in some in termites). This is a cell that appears at quiet ponds.

The paramecium genome has been sequenced (species: Paramecium tetraurelia), providing evidence for three whole-genome duplication.

In some ciliates, like Stylonychia and Paramecium, only UGA decoded as a stop codon, while UAG and UAA are reassigned as sense codons.

Texr resource:
Paramecium. (2008, December 18). In Wikipedia, The Free Encyclopedia. Retrieved 16:55, January 5, 2009, from

The Endocrine System Functions

The endocrine system is an information signal system much like the nervous system. However, the nervous system uses nerves to conduct information, whereas the endocrine system mainly uses blood vessels as information channels. Glands located in many regions of the body release into the bloodstream specific chemical messengers called hormones. Hormones regulate the many and varied functions of an organism, e.g., mood, growth and development, tissue function, and metabolism, as well as sending messages and acting on them.
  Subscribe in a reader Types of signaling
The typical mode of cell signaling in the endocrine system is endocrine signaling. However, there are also other modes, i.e., paracrine, autocrine, and neuroendocrine signaling. Purely neurocrine signaling between neurons, on the other hand, belongs completely to the nervous system.
A number of glands that signal each other in sequence is usually referred to as an axis, for example, the hypothalamic-pituitary-adrenal axis.
Typical endocrine glands are the pituitary, thyroid, and adrenal glands. Features of endocrine glands are, in general, their ductless nature, their vascularity, and usually the presence of intracellular vacuoles or granules storing their hormones. In contrast, exocrine glands, such as salivary glands, sweat glands, and glands within the gastrointestinal tract, tend to be much less vascular and have ducts or a hollow lumen.
Autocrine signaling
Autocrine signaling is a form of signalling in which a cell secretes a hormone, or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cell. This can be contrasted with paracrine signaling, intracrine signalling, or classical endocrine signaling.
Paracrine signaling is a form of cell signaling in which the target cell is near ("para" = near) the signal-releasing cell.
A distinction is sometimes made between paracrine and autocrine signaling. Both affect neighboring cells, but whereas autocrine signaling occurs among the same cell, paracrine signaling affects other cells. Two neurons would be an example of a paracrine signal.
Juxtacrine signaling is a type of intercellular communication which is transmitted via oligosaccharide, lipid or protein components of a cell membrane and may affect either the emitting cell or immediately adjacent cells.
It occurs between adjacent cells that possess broad patches of closely opposed plasma membrane linked by transmembrane channels known as connexons. The gap between the cells can only usually be between 2-4nm.

Small interfering RNA(siRNA) Animation

Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of 20-25 nucleotide-long double-stranded RNA molecules that play a variety of roles in biology. Most notably, siRNA is involved in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene. In addition to their role in the RNAi pathway, siRNAs also act in RNAi-related pathways, e.g., as an antiviral mechanism or in shaping the chromatin structure of a genome; the complexity of these pathways is only now being elucidated.
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siRNAs were first discovered by David Baulcombe's group in Norwich, England, as part of post-transcriptional gene silencing (PTGS) in plants. The group published their findings in Science in a paper titled "A species of small antisense RNA in posttranscriptional gene silencing in plants". Shortly thereafter, in 2001, synthetic siRNAs were shown to be able to induce RNAi in mammalian cells by Thomas Tuschl and colleagues in a paper published in Nature. This discovery led to a surge in interest in harnessing RNAi for biomedical research and drug development.
siRNAs have a well-defined structure: a short (usually 21-nt) double strand of RNA (dsRNA) with 2-nt 3' overhangs on either end:
Each strand has a 5' phosphate group and a 3' hydroxyl (-OH) group. This structure is the result of processing by dicer, an enzyme that converts either long dsRNAs or small hairpin RNAs into siRNAs.SiRNAs can also be exogenously (artificially) introduced into cells by various transfection methods to bring about the specific knockdown of a gene of interest. Essentially any gene of which the sequence is known can thus be targeted based on sequence complementarity with an appropriately tailored siRNA. This has made siRNAs an important tool for gene function and drug target validation studies in the post-genomic era.

HPV and Cervical Cancer Lecture

HPV stands for human papilloma virus. There are over 100 types of HPV. Some types produce warts on the hand, and some infect the genital area. Most seem to have no harmful effect.Some types of HPV can cause genital warts. Other types may cause changes in cells. These types are linked with cancers of the cervix, vulva, vagina, and anus. Almost 100% of cervical cancers have these types of HPV present.

Dr. Denise Galloway, Head of the Cancer Biology program at Fred Hutchinson Cancer Research Center, discusses her investigation into the natural history of HPV, a virus that has the potential to lead to cancer in HPV and Cervical Cancer: 25 Years from Discovery to Vaccine.