Article Armies

REGULATORY T CELLS(Treg) By Stephen Jones

Early development and differentiation of nascent T cells that migrate from bone marrow to become mature, na�ve T cells, which are capable of responding to antigen takes place inside the thymus. Around 1010 TCR (T cell receptor) variations are generated in developing T lymphocyte clones through a random process of somatic cell gene reorganization. During this process, often T-cells recognizing self-antigens are generated. Due to the ability of these self-reactive T-cells to elicit an autoimmune attack, they are permanently removed by the thymus through negative selection and clonal deletion. But, some of them manage to escape the thymic defenses and harbor themselves in the peripheral lymphoid organs. In periphery, T lymphocytes undergo further differentiation into effectors of various immune functions. One of many immunotolerance mechanisms that immune system has developed to distinguish between self and non-self antigens is regulatory T cells or Tregs. These cells are recently characterized specialized T-cell subsets that actively suppress a variety of immune responses. Researchers have broadly classified Tregs into natural and adaptive Tregs. Natural Tregs are CD4+CD25+ T-cells that originate in the thymus and play a significant role in immune homeostasis and protection against autoimmunity. Adaptive Tregs are non-regulatory CD4+ T-cells that have up-regulated CD25 expression during pathological and inflammatory conditions such as cancers and infections. Although the principal immunosuppressive mechanism of Tregs remains elusive, several in vivo experimental models have indicated that Tregs secrete large amounts of immunosuppressants including IL-9, IL-10 and TGF-β upon activation. These lymphokines are capable of inhibiting activation of Th1, Th2 cells and CTLs required for cell-mediated immunity, inflammation and antibody production. Certain recent experimental data and results even indicate that IL-2-IL-2R signaling is vital for development, maintenance, survival, expansion and suppressive activity of Tregs. Increased expression of certain other characteristic markers including CTLA-4, glucocorticoid-inducible tumor necrosis factor receptor (GITR) and OX40 has been identified on Tregs whose function inside these cells is still not clear. The TCRs displayed on Tregs are capable of recognizing and interacting with any peptide-MHC class II ligand having certain range of avidity. But, the contribution of TCR signaling and role of TCR-ligand interactions towards regulatory T-cell development needs to be determined. Several elegant experiment using transgenic mice and retrovirus mediate over expression studies, researchers have identified FoxP3, a transcription factor, to be a specific molecular marker essential for the development and function of Tregs. The primary evidence regarding the involvement of FoxP3 in the development of Tregs was provided by the experiments of Sakaguchi et al, (ref ?) in patients suffering from IPEX, a rare and fatal human autoimmune disorder. In these patients, mutated FoxP3 gene causes improper development of Tregs resulting in hyperactivation of T-cells reactive to self-antigens. Recently, experiments have clearly shown that retroviral mediated introduction of FoxP3 into conventional CD4+ T-cells converts them into regulatory T-cells. The emergence of regulatory T-cells and role of FoxP3 as a critical player in the negative control of a of various normal and pathological immune responses holds great promise for the development of novel therapies useful for the treatment of autoimmune diseases in humans. However, there are several questions that remain to be answered including the basic biology of the Tregs, various ligands responsible for thymic selection of these cells, the exact function of FoxP3 in relation with various markers present on Tregs and most importantly, the mechanisms by which Tregs exert their suppressive effects. A better understanding of manipulating FoxP3 and Tregs would enable us to harness the tremendous therapeutic potential in various clinical situations including Type I diabetes, Multiple sclerosis, GVHD, rheumatoid arthritis, allergy, and cancers. For more information about Regulator T-cells(Treg) visit : http://imgenex.com/Regulatory_cell.php.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Regulator T-cells(Treg).

Akt Family: Antibodies from Imgenex By Stephen Jones

Akt family of serine/threonine-directed kinases regulates a diverse array of biological processes, including cellular survival, proliferation, glucose homeostasis, and vascular tone and are important molecules in mammalian cellular signaling. The three widely expressed isoforms of PKB (PKB , PKB� and PKB ; also known as Akt1, Akt2 and Akt3, respectively) are each composed of an N-terminal PtdIns(3,4,5)P3- and PtdIns(3,4)P2-binding PH domain and a C-terminal kinase catalytic domain. Stimulation by numerous growth factors, cytokines, hormones and neurotransmitters can activate PKB/Akt in a phosphoinositide 3-kinase-dependent manner. Through receptor tyrosine kinases, these stimuli cause phosphoinositide 3-kinase activation, and generation of the membrane phospholipid PtdIns(3,4,5)P3. PtdIns(3,4,5)P3 then recruits PKB/Akt to the membrane, where it becomes phosphorylated (for PKB/Akt1) by upstream kinases, phosphoinositide-dependent kinase 1. Following the activation of PI 3-kinase, PKB isoforms are recruited from the cytosol to the plasma membrane through their interaction with PtdIns(3,4,5)P3 and/or PtdIns(3,4)P2 where they are thought to undergo a conformational change and become activated by phosphorylation of two residues. PKB can promote cell survival by inhibiting proteins that mediate apoptosis. Phosphorylation of BAD by PKB (and other AGC kinases) enables it to interact with 14-3-3 proteins, which prevents it from binding to Bcl-XL and thereby suppresses apoptosis. It directly phosphorylate and inhibit the caspase proteasesm, key executioners of apoptosis. PKBbeta, an essential gene for the maintenance of normal glucose homeostasis and is likely to represent a critical intermediate in the insulin signal transduction pathway. PKB activation might inhibit apoptosis by promoting the increased expression of survival molecules or the degradation of pro-apoptotic molecules. PKB also phosphorylates and activates endothelial nitric oxide synthase, thereby promoting angiogenesis (formation of new blood vessels). Inhibition of GSK3 following its phosphorylation by PKB has also been suggested to play a role in inhibiting apoptosis in neuronal cells. Thus it plays a key role in cancer progression by stimulating cell proliferation and inhibiting apoptosis, which suggests it, likely to be a hot drug target for the treatment of cancer, diabetes and stroke. For more information about �Akt Family� visit: http://www.imgenex.com/search_result.php?txtSearch=aktIMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Akt Family.

ATM (Ataxia Telangiectasia Mutated) Antibodies from Imgenex By Stephen Jones

ATM, the gene product mutated in the cancer susceptibility syndrome ataxia�telangiectasia, is related to proteins involved in DNA repair and cell-cycle control. It encodes a nuclear 350 kDa phosphoprotein containing a carboxy terminus phosphatidylinositol 3-kinase (Pl-3 kinase) catalytic domain shared by members of a superfamily of large eukaryotic proteins involved in intracellular signaling, DNA-damage induced cell cycle checkpoints, DNA repair and recombination. It was discovered as mutated proteins in patients with ataxia-telagiectasia (A-T), a severe genetic disorder characterized by cerebellar degeneration, neuromotor dysfunction, chromosomal instability, immune system defects, cancer predisposition, and acute sensitivity to ionizing radiations. In undamaged cells it is present as a dimer or oligomer molecule in which the kinase domain is silent because associated with the FAT region of another ATM monomer. Following DSB formation, it rapidly autophosphorylates on residue Serine 1981, and the inactive ATM dimers are converted (dissociated) into active ATM monomers. Active phosphorylated ATM molecules interact and phosphorylate downstream proteins that affect one or more of the cell cycle checkpoints. Some of the known substrates are the p53 protein and its ubiquitin ligase, MDM2; the Nbs1 protein; the Brca1 protein, which interacts with other repair proteins; the checkpoint kinase 2, Chk2; the Rad17 protein and the chromatin remodeling protein SMC1. Phylogenetic analyses reveal that the ATM protein is most closely related to several very large proteins that define a subgroup of the PI 3-kinase family which include the Schizosaccharomyces pombe Rad3 protein and its probable Saccharomyces cerevisiae homologue, Mec1p/Esr1p. Other proteins in the ATM family are S. cerevisiae Tor1p and Tor2p and their mammalian counterpart FRAP, which function, at least in part, by controlling progression through the G1 phase of the cell cycle. The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide and also assists cells in recognizing damaged or broken strands of DNA. It has been suggested that it acts as a lipid kinase, and feeds the phosphorylated lipids into signaling pathways to regulate cell-cycle progression or the activity of DNA-repair components. It regulates NF-κB activity and control the transcription of many genes that play important roles in the development and function of the immune system. In the DNA-damage response pathway, it acts upstream of p53 to induce cell cycle arrest at the G1/S and G2/M boundaries and a slowing of the S-phase. Signalling by ATM involves interactions with and phosphorylation of critical molecules, including the mitotic checkpoints Chk1 and Chk2. Apart from its role in ataxia telangiectasia (AT), ATM gene mutations have also been found in T-cell prolymphocytic leukaemia patients with no family history of AT and in non-Hodgkin�s lymphomas. For more information about �ATM (Ataxia Telangiectasia Mutated)� visit : http://www.imgenex.com/antibody_details.php?catalog=IMG-80237IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about ATM (Ataxia Telangiectasia Mutated).

Fundamental Immunology, Basic Immunology and Allergy Immunology By Stephen Jones

Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade our systems and cause disease. The immune system is made up of a network of cells, tissues, and organs that work together to protect the body. The immune system is the body�s natural defence in combating organisms. The immune system usually have two lines of defence: the innate immune system representing a non-specific (no memory) response to antigen (substance to which the body regards as foreign or potentially harmful) and the adaptive immune system, which displays a high degree of memory and specificity. The innate system represents the first line of defence to an intruding pathogen and includes various cells like the natural killer (NK) cells, mast cells dendritic cells and phagocytes. Besides there are molecules like complement, acute phase proteins (APP) and interferons (IFNs) which work in concert with the cells of the innate immune system and which foster close functional links with their adaptive counterpart. The adaptive immune system is further divided into humoral and cellular components. Cell-mediated immunity, also known as delayed-type hypersensitivity (DTH) or Type IV Hypersensitivity, is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. The humoral immune response (HIR) is the aspect of immunity that is mediated by secreted antibodies, produced in the cells of the B lymphocyte lineage (B cell). When activated by foreign antigen, B cells undergo proliferation and mature into antibody secreting plasma cells which posses the ability to secrete soluble proteins (antibodies). Antibodies which are classified into five different types (known as isotypes), namely IgM, IgG, IgA, IgE and IgD, have two roles to play - the first is to bind antigen and the second is to interact with host tissues and effector systems in order to ensure removal of the antigen. Thus the immune system generally is protective, however the same immunologic mechanisms that defend the host at times may result in severe damage to tissues and, occasionally, may cause death. Conceptualizing the natural antigen- antibody development & interaction, Imgenex Corp. develops and commercializes novel reagents for the scientific study of human biology and disease and for the production of new diagnostic assays and potential therapies of such diseases. These novel reagents include antibodies, gene and protein expression systems, and arrays of various cells and tissues for use in studies of functional genomics. Areas of biological interest at IMGENEX include cancer, apoptosis (programmed cell death), molecular signaling pathways, cellular aging, and metabolic and infectious diseases. For more information about immunology visit : http://imgenex.com/Immunology.phpIMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about immunology.

Search Engine Placement: Highlight The Presence of Your Site in SERPs By Auroin

Research reveals that about 80% of people looking for products or services on the Internet start by searching through one of the major search engines. Millions of internet users are found within the U.S. alone and over one billion internet users worldwide. Without a high search engine placement, those seeking to buy your products won't find them and will turn to your competitors. Your products and services are sought after by your potential customers everyday. It is vital for your website to have a better search engine placement for your specific keyword to drive the visitors to your website. Knowing how your customers are searching for your products and services, and being found at the top of Google, Yahoo and MSN for those exact search terms are crucial. Search engine placement is a science of modification of a website using both on-page as well as off-page search engine optimization methods so that a site gets a higher search engine placement. The Search engine placement techniques are composed of the following: � Analyzing your existing WebPages � Analyzing the keywords compared to various search engine databases. � Optimizing or creating new pages that include contents related to your key phrases. � Submitting your pages to the major search engines. � Monitoring and reporting on your position on each search engine. Every day, web surfers search for information on products and services. Throughout the day, these consumers enter millions of queries at major search engines. Web sites that lack regular optimization tend to get buried in search engine result pages where consumers rarely look. Even if you have a great web site, without a high search engine ranking, hardly anyone will find it. Optimizing a web site on a regular basis increases its chances of appearing at the top of the search engine listings when a user makes a query. Search engine placement can be a very tough job. It involves continuous efforts of optimizing content, submitting web sites and analyzing search engine rankings. If optimization is done correctly, your web site may just capture a top spot in the rankings. If things go wrong however, it may drown in a sea full of millions of other web sites. A reliable optimization service will save you from the above anxiety. If you possess an online business and you don�t find noticeable boost in sales then it might be because your website does not have the right search engine placement. If you are planning on making some extra cash make sure that your website is fully optimized so that people can find you on search engines. You will be pleased for having worked on this one!For More Information regarding Search Engine Placement Please Visit http://www.auroin.com/seo-articles/search-engine-placement.htm

Transcriptional Factors And Regulators By Stephen Jones

All the cellular processes in living cells such as growth, development, morphogenesis and cellular differentiation are a product of gene expression programs involving complicated transcriptional regulation of several genes. This process of transcriptional regulation is tightly controlled and coordinated by proteins called transcriptional regulators. These transcriptional regulators and factors are DNA-binding proteins that bind to the promoter or enhancer sequences on the DNA and facilitate either transcriptional repression or activation. There are three principal types of transcription factors. These include basal transcription factors, upstream transcription factors and inducible transcription factors. The basic structure of every transcriptional factor mainly contains a DNA-binding domain and an activator domain. DNA-binding motifs found in transcription factors include zinc-finger, helix-loop-helix, helix-turn-helix, leucine zipper and high-mobility groups, based on which transcription factors are classified. The activator domain of these transcription factors interacts with components of transcription machinery such as RNA polymerases and associated transcription regulators. Regulation of transcriptional factors is a complex mechanism that ensures exact spatio-temporal expression of genes. In response to a specific cellular stimulus, these trans-regulatory factors are activated in a sequential manner. Upon activation, these factors recruit transcriptional co-regulators such as histones that function as co-activators or co- repressors and aid in modifying chromatin structure. Altered activation of these regulators is often associated with various pathologies such as chronic disorders and malignancies. Recent studies are concentrating on developing improved disease treatment strategies through identification of different transcription factor-binding patterns and blocking them. There are several families of trans-regulatory factors that control critical cellular signaling cascades involved in cell proliferation, survival, lineage development and cellular differentiation. These include Rel/NF-kB family, AP-1 family, STAT family of transcription factors, homeodomain proteins, DNA-binding proteins, POU transcription factors, nuclear hormone receptor family, p53 family and E2F family.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA.Find out more information about Transcriptional Factors .

Data Validation through Tissue Analysis By Stephen Jones

IMGENEX History-Array� tissue array slides are a simple, powerful, inexpensive, yet highly efficient method for expression analysis or localization studies of molecular targets at the DNA, RNA or protein level. The existing body of literature using Western blot analysis has been primarily defined with data from tumor, immortal, and primary cells growing in vitro. Collectively, results obtained over decades have been integral to the dogma that up- and down-regulation of proteins can be leveraged as Biomarkers of normal development, homeostasis, and disease. However, in contrast to tissues which are composed of multiple cell types, cell lines growing in culture which theoretically consist of clonal populations. Thus, validation or modification of western blot parameters collectively established from decades of cell line data in tissue lysates is key for Biomarker discovery. IMGENEX can provide you with normal post mortem, cancerous, diseased, and normal adjacent clinical specimens matching your requirements. Custom collection protocols are welcomed. Specimens are available as frozen or formalin-fixed, paraffin-embedded tissue blocks, and include clinical case and detailed pathology reports, as well as final diagnosis and staging. Learn more about this service by visiting our website, or downloading our Tissue Procurement literature. Related Products * Tissue Arrays * Single Tissue Slides * Tissue & Cell Lysates * Extraction/ Fractionation Kits * INSTA-Blot Ready2use WB MembranesIMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA.Find out more information about Tissue Arrays.

NF-kB Activation: Elucidating Upstream Events By Stephen Jones

NF-kB (Nuclear Factor-KappaB) is a heterodimeric protein composed of different combinations of members of the Rel family of transcription factors. The Rel/NF-kB family of transcription factors are involved mainly in stress-induced, immune, and inflammatory responses. The classical pathway for activation of NF-kB, a key transcriptional regulator of the immune system, is controlled by the IKK complex. Activated IKK phosphorylates IkB which is ubiquitinated and rapidly degraded, allowing NF-kB to translocate from the cytoplasm to the nucleus where it activates gene transcription. However, the mechanisms regarding IKK activation have been elusive. Now CARMA1, Bcl-10, and MALT1 are helping to fill in the blanks of IKK activation. These proteins are downstream of the T cell receptor (TCR) and upstream of the IKK complex (Fig. 1). Antigen-TCR signaling in the adaptive immune system leads to PKC-q activation and formation of an oligomerization-ubiquitination (Ub)-phosphorylation (P) pathway leading to activated IKK. Oligomerization-Ub-P pathways have also been found to mediate NF-kB activation through TLR (Toll-like receptor) signaling; suggesting these emerging IKK activation pathways may play key roles in regulating both adaptive and innate immunity. IMGENEX offers a complete line of antibodies, inhibitors, ELISA assays, and RNAi kits to complement your NF-kB & TLR signaling studies. Visit our IMGENEX to learn how we can help you accelerate your research.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation,San Diego, USA. Find out more information about NF-kB.

GPR83: A Novel Treg Expressed Cell Surface Marker By Stephen Jones

GPR83 is a member of the Orphan-A G-Protein coupled receptor family, and has anunknown ligand. It has been previously reported in various regions of the brain, within a subset of T-lymphocytes, and by RT-PCR at low levels in heart, kidney, liver, and otherorgans. As research continues to unravel the molecular basis of regulatory T cells (Treg), FOXP3 has emerged as a key player in orchestrating development and function of natural Treg. Two recent publications identified GPR83 as specifically upregulated in fresh and activated CD4+ CD25+ Treg cells. Both groups performed gene expression profiling on Treg, and other T cells to identify differentially regulated genes. Sugimoto et al. performed additional mRNA and protein expression analysis based on the results of their micro array analysis using RT-PCR as well as FACS analysis of GPR83 using anti-GPR83 antibody. These recent findings suggest that GPR83 may be useful as a specific and stable cell surface marker with modulatory properties, and a key molecule for further characterizing the molecular basis of Tregs. IMGENEX proudly offers this Flow and IHC positive GPR83 antibody (IMG-71561), as well as other GPR83, FOXP3, and CD marker antibodies for your Treg research. Key Publication Findings �GPR83 is upregulated in both murine and human Treg � Gene analysis, mRNA, and protein expression show that GPR83 is upregulated in FOXP3+ cells � GPR83 is expressed in both fresh and activated Treg � GPR83 appears to be FOXP3 dependent, although Hansen et al. suggests that induction of FOXP3+ Treg by GPR83 occurs in vivo, suggesting a more complex relationship � GPR83 is found in both Thymus and Spleen/LN CD4 and CD25 cells � Foxp3 retroviral transduced CD25- CD4+ cells induces GPR83 expression at much higher levels than mock-transduced cells � Suggests a possible ligand that binds to GPR83 in vivo which confers to these cells suppressive activity.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about GPR83 & FOXP3 Treg.

QuikChIP Chromatin Immunoprecipitation Kits By Stephen Jones

IMGENEX QuikChIP Certified Antibodies The Basics... The principle of the ChIP assay is simple: selective enrichment of a chromatin fraction containing a specific target. However, the process can be technically challenging. It is with these challenges in mind that IMGENEX developed the QuikChIP Kit for chromatin immunoprecipitation. QuikChIP includes optimized ready-to-use buffers and inhibitory reagents, as well as a comprehensive technical manual. * Quick & simple * Optimized ready-to-use buffers & protocol * Useful for Histone and non-histone proteins Reagents for 25 ChIP assays and sheared Chromatin preparations ............................................................................... QuikChIP Certified Antibodies IMGENEX offers a growing number of antibodies that have been validated for use in ChIP assays and we are continually testing and validating new products for use in ChIP. Below is a list of our currently available QuikChIP Certified Antibodies. Be sure to check our website often as we are releasing new antibodies every week! Sheared Chromatin IMGENEX QuikChIP� Sheared Chromatin is ready-to-use, sheared, cross-linked chromatin prepared from mammalian cell extracts. This novel product enables researchers to carry out ChIP assays in the absence of cell culture facilities or sonication equipment. It is also useful as a sheared, cross-linked chromatin positive control, alongside your own cell extracts. Conditions for cell culture, DNA-protein cross-linking, and the sonication shearing process have been optimized for each human and mouse cell type.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation,San Diego, USA. Find out more information about Chromatin Immunoprecipitation.

Apoptosis Programmed Cell Death By Stephen Jones

Apoptosisis regulated by death domain (DD) and/or caspase recruitment domain (CARD) containing molecules and a caspase family of proteases. A novel CARD domain containing protein was recently identified and designated ARC for apoptosis repressor with CARD (1). For more details read out the article: Coined in the 1960's,apoptosis is derived from the Greek word apopiptein which means to fall off from. Apoptosis can be induced by a number of stimuli including UV damage, irradiation, drug treatment, or tumor necrosis factor. Once induced, apoptosis can, in turn, act through a number of different cell death signaling pathways. The number of apoptosis and 'programmed cell death' related kits and reagents available to the market have increased significantly over the last few years. This is in large part the result of increasing evidence implicating the role of apoptosis in a number of significantly relevant disease processes including certain autoimmune diseases, transplantation rejection, and neurodegenerative diseases. IMGENEX offers over 200 Apoptosis related antibodies, as well as ELISA kits, caspase inhibitors, active caspase detection kits, apoptosis detection kits, and mitochondrial permeability detection kits.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Apoptosis.

GPCRs: Exploring New Paradigms By Stephen Jones

As one of the largest and most diverse protein families in nature, the G-protein coupled receptor (GPCR) superfamily play important roles in a variety of biological and pathological processes such as development and proliferation, neuromodulation, angiogenesis, metabolic disorders, inflammation, and viral infection. Not surprisingly, it is one of the most targeted protein families in pharmaceutical research today (Schlyer 2006). All members of this superfamily share a similar seven transmembrane domain, but are grouped on the basis of shared sequence motifs into the following broad classes: Class A Rhodopsin-like Class B Secretin-like Class C Metabotropic glutamate/pheromone Class D Fungal pheromone Class E cAMP receptors Frizzled/Smoothened Vomeronasal receptors Putative/unclassified The pharmaceutical industry has focused on development of modulators to this protein family, but GPCRs also represent an attractive target as biomarkers. Recent studies have implicated endothelin receptors, chemokine receptors and lysophosphatidic acid receptors in tumorgenesis and metastasis, and a recent in silico analysis found a number of GPCRs that were up-regulated in various cancers which suggests not only targets of therapeutic value, but of diagnostic and prognostic value as well. A summary of these up-regulated receptors is below. Lung cancer Edg2, P2Y purinoceptor 6, PAR-2, PAR-3, GPR68 Breast cancer CCR1, CXCR-4, PAR-2 Prostate cancer Beta 2 adrenergic receptor, CXCR-3, CXCR-4, GPR68 Melanoma Edg6, PAR-2, mGluR1 Gastric cancer CXCR-4, P2Y purinoceptor 5 Lymphoma Beta 2 adrenergic receptor, Edg1, CCR7 While research continues, it is evident that GPCRs are critical in countless biological functions--and disfunctions. While the emphasis is on their role in drug development, it is becoming increasingly clear that G-protein coupled receptors will play a critical role as indicators of disease with diagnostic and prognostic potential. IMGENEX carries over 900 IHC, WB, and flow validated GPCR antibodies. View our complete GPCRs antibody list grouped by class and family. Also see our complete list of Tissue Microarray slides--perfect for GPCR localization.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation,San Diego, USA. Find out more information about GPCRs.

Epigenetic and Signal Transduction Reagents By Stephen Jones

IMGENEX offers over 90 Chromatin, DNA Methylation & Repair, and DNA Fragmentation-related antibodies, many of which have been cited in numerous peer-reviewed journals. These antibodies have been used to study transcriptional silencing, identify DNA-protein interactions, and characterize the sequence of molecular binding events. Surging interest in understanding the mechanisms of epigenetics is attracting researchers worldwide from a wide variety of scientific disciplines. Epigenetics is the study of the heritable changes in gene function that occur without changes in DNA sequence. It is becoming increasingly apparent that an epigenetic phenomenon is integral to both normal and aberrant gene regulation. Histone proteins are thought to be the major carriers of epigenetic information. Histones form the nucleosomal complexes that make up the eukaryotic chromatin, which packages and organizes DNA in the nucleus. The nucleosome, the basic repeating subunit of chromatin, is composed of DNA coiled around an octamer of two molecules, each with four core histone proteins: H2A, H2B, H3 and H4. Each core histone is composed of a structured, three-helix domain called the "histone fold" and two unstructured tails. The N-terminal histone tails extend outward from the DNA to interact with the nuclear environment where they are the targets of multiple, diverse signaling pathways. Signal transduction pathways impinging on the N-terminal histone tails result in a number of post-translational modifications including acetylation, phosphorylation, poly(ADP-ribosylation), ubiquitination and methylation. These modifications play critical roles in regulating chromatin structure and gene expression.IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation,San Diego, USA. Find out more information about Epigenetics.

Science and The Law of Attraction By

If the Law of Attraction is to explain how everything that we have comes into our lives; if The Secret is to explain how we come to our state of wealth, our state of health and our state of happiness, then some further questions need to be answered. Many people accept that the Law of Attraction and The Secret can be used to gain whatever wealth a person desires. Many believe that money, jobs, houses, cars and any other item of material wealth will materialize if the tenets of The Secret are followed. The big names associated with The Secret who appear to have used its principles to gain their success add credibility to the concept. The developments in Quantum Physics assist in steering our reliance on modern physics for explaining happenings in the universe to other plausible explanations. Since knowledge is not static and the arena of physics has been developing so quickly, the explanations offered by Quantum Physics merit exploring. The recent discovery of silica on Mars, proving the once existence of water on that planet, could be explained as a mere accident. But the knowledge and energies of the Universe could also be used as an explanation. After all those years of exploration, it took a ceased wheel to drag in the soil to uncover the silica and prove the water theory. Could that mechanical failure and ensuing discovery be explained by The Secret and the Law of Attraction? Could it be explained as the Universe, through its energies, knowing what the scientists so badly wanted and fulfilling their wishes? Is the discovery a manifestation of the wants and desires of the scientists and people who were willing to spend millions (billions?) on the project and spend countless hours monitoring and evaluating the data from the spacecraft? Is it a case of wanting something so badly that the Universe gives it to you? Is it a case of the Universe modifying our inadequate technology by something so simple as a broken wheel to ensure our efforts and wishes are met? Far fetched ideas? Maybe. Maybe not. Had that one incident not occurred, the mission would have probably ended without providing the evidence of water having existed on Mars. It seems that at some level it is plausible that The Secret and the Law of Attraction do apply to such discoveries. How about past scientific discoveries? How many came at a time when the world needed a great discovery or when a change in thinking was needed to send science in a new direction. By accident Sir Alexander Fleming discovered penicillin in 1928. That discovery of the first antibiotics transformed the practice of medicine. Methods of mass production were established by American companies and by D Day in 1945 enough of the antibiotic was available to treat all the bacterial infections incurred by the troops. Was this discovery really an accident? Fleming just happened to notice the effect mold growing on one of his slides had on the bacteria he had placed there. He just happened to notice this as he was cleaning his lab. Was it really an accidental discovery or did the deep desire of scientists to find an effective means of combating infections lead the Universe to provide the circumstances for the discovery. The Secret would support this latter hypothesis. Another such discovery was Frederick Banting�s discovery of insulin. It was his deep-seated belief and his vision that allowed him to convince the University of Toronto physiology department head to give him laboratory space and an assistant. This discovery has saved millions of lives; over 15 million people today have diabetes who, in all likelihood, would have died were it not for insulin. This discovery also revolutionized the practice of medicine. Did the energies of the Universe conspire to ensure the discovery? Did the Universe play a role in having the department head give against his beliefs after having actually scoffed at Banting�s ideas? The Secret and the Law of Attraction would agree on the intervention of the Universe. So would many past and present scientists and philosophers. What the Power is I cannot say All I know is That it exists. Alexander Graham Bell It is matter of personal belief as to what extent you accept that The Secret And the Law of Attraction have been instrumental in the big scientific discoveries over time. But to know if you see merit in the theory, you need to be aware of the principles in and behind The Secret. Once you know those principles, then you can make an informed decision. I believe there is merit in The Secret. I am convinced that it explains a lot of things that I see happen - both good things and things that are not so good. I believe that it explains to a great degree the prevalence of some illnesses in our society and the devastating medical conditions that some people and families find themselves in. But I see areas where I have difficulty accepting that the Law of Attraction or The Secret produced the results. The next article will address one of those areas.Working with people in a medical setting who span the spectrum from happiness to despair, the author has come to appreciate how people create their own reality. The author believes this creation occurs at all levels, including scientific discoveries. More information is found at Secret of Attraction.