Long-Term Potentiation LTP

Long-term potentiation (LTP) is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength,LTP is widely considered one of the major cellular mechanisms that underlies learning and memory.

LTP shares many features with long-term memory, making it an attractive candidate for a cellular mechanism of learning. For example, LTP and long-term memory are triggered rapidly, each depends upon the synthesis of new proteins, each has properties of associativity, and each can last for many months. LTP may account for many types of learning, from the relatively simple classical conditioning present in all animals, to the more complex, higher-level cognition observed in humans.

At a cellular level, LTP enhances synaptic transmission. It improves the ability of two neurons, one presynaptic and the other postsynaptic, to communicate with one another across a synapse. The precise molecular mechanisms for this enhancement of transmission have not been fully established, in part because LTP is governed by multiple mechanisms that vary by species and brain region. In the most well understood form of LTP, enhanced communication is predominantly carried out by improving the postsynaptic cell's sensitivity to signals received from the presynaptic cell. These signals, in the form of neurotransmitter molecules, are received by neurotransmitter receptors present on the surface of the postsynaptic cell. LTP improves the postsynaptic cell's sensitivity to neurotransmitter in large part by increasing the activity of existing receptors and by increasing the number of receptors on the postsynaptic cell surface.

LTP was discovered in the rabbit hippocampus by Terje Lømo in 1966 and has remained a popular subject of research since. Many modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between LTP and behavioral learning. Still others try to develop methods, pharmacologic or otherwise, of enhancing LTP to improve learning and memory. LTP is also a subject of clinical research, for example, in the areas of Alzheimer's disease and addiction medicine.

Molecular Collapse of Evolution

NEWWET LIMB REGENRATION

Oxygen Transport

ParM and Plasmid Segregation

DNA segregation by ParM - ParM binds to DNA-binding proteins, called ParR (orange proteins) around which segments of genomic DNA are coiled. Sister plasmid segregation is achieved through bidirectional insertional polymerization of the ParM filaments.

Passenger Proteins

Phagocytosis Video

Precipitor - Affinity Magnetic High Throughput Immunopreciptor

Abnova's Precipitor™ system is automated magnetic bead platform for high throughput precipitation and purification of proteins. Combining 96 deep well plate with affinity conjugated magnetic beads, Precipitor™ easily handles 16 different assays simultaneously by transferring beads from one well to the next for mixing, binding, washing, and elution reactions via the robotic action of parallel magnetic rods. It simplifies the routine yet labor intensive process, and addresses the needs of rigorous proteomic screening and biomarker discovery applications such as immunoprecipitaton (IP, ChIP, RIP), recombinant protein purification, and protein-protein interaction. Precipitor™ delivers reproducible and consistent results by obviating the drawbacks of manual operation. Its integrated onscreen display allows easy change of parameters tailored to your experiment. Moreover, you can select from large scope of available antibodies reagents to accelerate your research!

Photon - 96 well Chemiluminescence Reader

Pronucleus microinjection Video

Radiation of DNA and Response of Different Cells to Radiation.

Rap5 protein and endosome fusion under microscope

Replication of HCV

RNAi Transfection Video

Role of Tubulins on Forming ER network

Signal Recognition Particle Video

Size Analogies of Bacteria and Viruses

Specific (Adaptive) Immunity Humoral and Cell Mediated

Spirogyra Cell Colonies Video

Spire mechanism Video

Stem Cells Heart cells Grown from Mouse Stem Cells Video

Stereoclia and Hair cells

Stereocilia are apical modifications of the cell, which are distinct from cilia and microvilli, but closely related to the latter.Though their name is more similar to cilia, they are actually more closely related to microvilli, and some sources consider them to be a variant of microvilli rather than their own distinct type of structure. It is a long projection of cell membrane, similar in structure to microvillus

Mammalian Molecular Clock Model

 Molecular Clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation. The molecular data used for such calculations is usually nucleotide sequences for DNA or amino acid sequences for proteins. It is sometimes called a gene clock or evolutionary clock.

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Angiogenic Switch and VEGF

Tuberculosis Video

Tumor Vasculature Video

Visualization of the Nuclear Import and Nuclear Export

AZT Mechanism of Antiviral Activity Video

Asymmetric division Video

Apoptosis Video

Adhesion junctions at epithelial cells

Acetyl CoA enzyme

Triskelion ( clathrin)

The triskelion shape of the clathrin molecule enables it to form the polyhedral protein network that covers clathrin-coated pits and vesicles. Domains within the clathrin heavy chain that are responsible for maintaining triskelion shape and function were identified and localized. Sequences that mediate trimerization are distal to the carboxyl terminus and are adjacent to a domain that mediates both light chain binding and clathrin assembly. Structural modeling predicts that within this domain, the region of heavy chain-light chain interaction is a bundle of three or four alpha helices.

Sandwich ELISA Isotype detection

Sandwich ELISA is performed to measure the amount and serological class of antibodies made by an immunized animal or present in the serum of patients. Anti-immunoglobulin antibodies is used as the specific and sensitive agents of detection.

Zirconocene beta-Hydride Transfer with HOMO Isosurface Video

HIV-Mode of action of NNRTIs

NNRTIs are a class of anti-HIV drugs. When one NNRTI is used in combination with other anti-HIV drugs – usually a total of 3 drugs – then this combination therapy can block the replication of HIV in a person's blood.

NNRTIs, sometimes referred to as "Non-Nucleoside Analogues" – or "non-nukes" for short – prevent healthy T-cells in the body from becoming infected with HIV.

When HIV infects a cell in a person's body, it copies it's own genetic code into the cell's DNA. In this way, the cell is then "programmed" to create new copies of HIV. HIV's genetic material is in the form of RNA. In order for it to infect T-cells, it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.

NNRTIs attach themselves to reverse transcriptase and prevent the enzyme from converting RNA to DNA. In turn, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell, and prevents the cell from producing new virus.

DNA Gel Preparation

Morphine

Morphine (INN) (pronounced /ˈmɔrfiːn/) (MS Contin, MSIR, Avinza, Kadian, Oramorph, Roxanol, Kapanol) is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was discovered in 1804 by Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more widely used after the invention of the hypodermic needle in 1857.

Morphine is the most abundant alkaloid found in opium, the dried sap (latex) derived from shallowly slicing the unripe seedpods of the opium, or common or edible, poppy, Papaver somniferum. Morphine was the first active principle purified from a plant source and is one of at least 50 alkaloids of several different types present in opium, Poppy Straw Concentrate, and other poppy derivatives. Morphine is generally 8 to 17 per cent of the dry weight of opium, although specially-bred cultivars reach 26 per cent or produce little morphine at all, under 1 per cent, perhaps down to 0.04 per cent. The latter varieties, including the 'Przemko' and 'Norman' cultivars of the opium poppy, are used to produce two other alkaloids, thebaine and oripavine, which are used in the manufacture of semi-synthetic and synthetic opioids like oxycodone and etorphine and some other types of drugs. Morphine can be found in low to intermediate concentrations in the Iranian poppy (P. bracteatum), although this poppy is most often used for codeine and thebaine production. Higher, industrially useful concentrations of morphine are found in the oriental poppy (P. orientale). Lower concentrations may be found in a handful of other species in the poppy family, as well as in some species of hops and mulberry trees. Morphine is produced most predominantly early in the life cycle of the plant. Past the optimum point for extraction, various processes in the plant produce codeine, thebaine, and in some cases low quantities of hydromorphone, dihydromorphine, dihydrocodeine, tetrahydrothebaine, and hydrocodone. The human body also produces small amounts of morphine and metabolises it into a number of other active opiates.

In clinical medicine, morphine is regarded as the gold standard, or benchmark, of analgesics used to relieve severe or agonizing pain and suffering. Like other opioids, e.g. oxycodone (OxyContin, Percocet, Percodan), hydromorphone (Dilaudid, Palladone), and diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain. Morphine has a high potential for addiction; tolerance and psychological dependence develop rapidly, although physical addiction may take several months to develop.

Stem Cells: Programming and Personalized Medicine

Rudolf Jaenisch is one of the founders of transgenic science (gene transfer to create mouse models of human disease). His lab has produced mouse models leading to new understanding of cancers and various neurological diseases.

He received his doctorate in medicine from the University of Munich in 1967. He came to the Whitehead from the University of Hamburg in Germany, where he was head of the Department of Tumor Virology at the Heinrich Pette Institute.

Jaenisch received the 2002 Robert Koch Prize for Excellence in Scientific Achievement. In 2003, he was awarded the Charles Rodolphe Brupbacher Prize for basic research in oncology and was elected a member of the National Academy of Sciences.

Jaenisch is a fellow of the American Academy of Arts and Sciences and the American Academy of Microbiology, and a member of the American Association for the Advancement of Science

Competent Cell Preparation

Antibody Array for Protein Expression Profiling

Ionic Regulation Across Cell Membranes

How Anti-depressants Work

Messages pass from neuron to neuron using chemical messengers called neurotransmitters. The messages can pass on information about emotions, behavior, body temperature, appetite, or many other functions. The type of information sent depends on which neurons are activated and what part of the brain is stimulated.

A message passes from a sending neuron to a receiving neuron. The neurotransmitters leave the sending neuron and enter the space between the sending and receiving neurons. This space is called the synapse. The neurotransmitters then hook up to a receptor on the receiving neuron to deliver their message.

Once neurotransmitters have sent their message, they return and can be reabsorbed by the sending neuron in a process called reuptake. Reuptake allows the messengers to be reused. Two of these neurotransmitters are serotonin and norepinephrine. Low levels of serotonin and norepinephrine in the synapse are associated with depression and sadness. Some medications used to treat depression work by increasing the amount of certain neurotransmitters that are available to carry messages.

Each type of antidepressant works on brain chemistry a little differently. All antidepressant medications influence how certain neurotransmitters, especially serotonin and norepinephrine, work in the brain.

SSRIs and tricyclic antidepressants. Antidepressants, such as selective serotonin reuptake inhibitors, or SSRIs, and tricyclic antidepressants, work by slowing or blocking the sending neuron from taking back the released serotonin. In that way, more of this chemical is available in the synapse. The more of this neurotransmitter that is available, the more likely the message is received, and depression is reduced. To learn more about how these antidepressants work, see Tricyclic Antidepressants (TCAs) and Selective Serotonin Reuptake Inhibitors (SSRIs).

Intersubjectivity and Mirror Neurons

Intersubjectivity and Mirror Neurons

Collagen

Collagen is a group of naturally occurring proteins. In nature, it is found exclusively in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content. Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc.

In muscle tissue it serves as a major component of endomysium. Collagen constitutes 1% to 2% of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles. Gelatin, which is used in food and industry, is collagen that has been irreversibly hydrolyzed.

Fatty Acids Transport

Regulation of the mitochondrial CoA Acetyl-CoA ratio

Colony-stimulating factor

Colony-stimulating factors (CSFs) are secreted glycoproteins which bind to receptor proteins on the surfaces of hemopoietic stem cells and thereby activate intracellular signaling pathways which can cause the cells to proliferate and differentiate into a specific kind of blood cell (usually white blood cells, for red blood cell formation see erythropoietin).

They may be synthesized and administered exogenously. However, such molecules can at a latter stage be detected, since they differ slightly from the endogenous ones in e.g. features of posttranslational modification.

Hemopoietic stem cells were cultured  on a so-called semi solid matrix which prevents cells from moving around, so that if a single cell starts proliferating, all of the cells derived from it will remain clustered around the spot in the matrix where the first cell was originally located, and these are referred to as "colonies." It was therefore possible to add various substances to cultures of hemopoietic stem cells and then examine which kinds of colonies (if any) were "stimulated" by them.

The substance which was found to stimulate formation of colonies of macrophages, for instance, was called macrophage colony-stimulating factor, for granulocytes, granulocyte colony-stimulating factor, and so on.

The colony-stimulating factors are soluble, in contrast to other, membrane-bound substances of the hematopoietic microenvironment. This is sometimes used as the definition of CSFs. They transduce by paracrine, endocrine or autocrine signaling.

Conformational Transitions During Protein Folding

A beautiful representation (amino acid distance matrix) of the conformational transitions which a protein undergoes during folding. The bias-exchange metadynamics simulation is described in Pietrucci & Laio, J. Chem

GCSF Protein Folding Illustration Movie

Granulocyte Colony-Stimulating Factor (G-CSF or GCSF) is a colony-stimulating factor hormone. It is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to pulse them out of the marrow into the blood. It also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.

G-CSF is also known as Colony-Stimulating Factor 3 (CSF 3).




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Biological function

G-CSF is produced by endothelium, macrophages, and a number of other immune cells. The natural human glycoprotein exists in two forms, a 174- and 180-amino-acid-long protein of molecular weight 19,600 grams per mole. The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by recombinant DNA (rDNA) technology.

Mouse granulocyte colony-stimulating factor (G-CSF) was first recognised and purified in Australia in 1983, and the human form was cloned by groups from Japan and the United States in 1986.

The G-CSF-receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates proliferation and differentiation into mature granulocytes.

Genetics

The gene for G-CSF is located on chromosome 17, locus q11.2-q12. Nagata et al. found that the GCSF gene has 4 introns, and that 2 different polypeptides are synthesized from the same gene by differential splicing of mRNA.

The 2 polypeptides differ by the presence or absence of 3 amino acids. Expression studies indicate that both have authentic GCSF activity.

It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the G-CSF factor stem-loop destabilising element.

Therapeutic use

G-CSF stimulates the production of white blood cells (WBC). In oncology and hematology, a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery from neutropenia after chemotherapy, allowing higher-intensity treatment regimens. Chemotherapy can cause myelosuppression and unacceptably low levels of white blood cells, making patients prone to infections and sepsis. However, in a Washington University School of Medicine study using mice, G-CSF is shown to lessen the density of bone tissue even while it increases the WBC count; if this is found to occur in human cases it would necessitate increased consumption of calcium and vitamins A and D, and maybe drug therapy.

G-CSF is also used to increase the number of hematopoietic stem cells in the blood of the donor before collection by leukapheresis for use in hematopoietic stem cell transplantation. It may also be given to the receiver, to compensate for conditioning regimens.

Itescu planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus SDF (stromal cell-derived factor) directly to the heart.

The recombinant human G-CSF synthesised in an E. coli expression system is called filgrastim. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim. Filgrastim (Neupogen®) and PEG-filgrastim (Neulasta®) are two commercially-available forms of rhG-CSF (recombinant human G-CSF). The PEG (polyethylene glycol) form has a much longer half-life, reducing the necessity of daily injections.

Another form of recombinant human G-CSF called lenograstim is synthesised in Chinese Hamster Ovary cells (CHO cells). As this is a mammalian cell expression system, lenograstim is indistinguishable from the 174-amino acid natural human G-CSF. No clinical or therapeutic consequences of the differences between filgrastim and lenograstim have yet been identified, but there are no formal comparative studies.