CTLA4 (CD152) is a member of a class of cell surface molecules capable of terminating early events in the receptor-mediated signaling cascade. It is a 41–43 kDa,type 1 transmembrane glycoprotein of the immunoglobin superfamily having 223 amino acids in length. The extracellular architecture of CTLA4 is characterized by a single IgV-like domain containing the B7- 1 (CD80)/B7-2 (CD86) ligand-binding site. Expression of CTLA4 is dependent both on TCR stimulation by the antigens and CD28-B7 engagement. The costimulatory CTLA4 pathway, attenuates or downregulates T cell activation and CTLA4 is designed to remove body cells displaying "foreign" epitope, such as virus-infected cells, cells containing intracellular bacteria, and cancer cells with mutant surface proteins. The[..]

The MAPK (Mitogen-Activated Protein Kinase) cascades play a pivotal role in many aspects of cellular functions, and are evolutionarily conserved from yeast to mammals. In Saccharomyces. cerevisiae, there are five MAP kinase signal transduction pathways that regulate mating, filamentous growth, high osmolarity response, maintenance of cellular integrity, and ascospore formation. The best-defined yeast MAPK pathway in S. cerevisae is involved in the mating of haploid cells. Yeast may exist either as haploid or diploid cells. The haploid cells have two sexual phenotypes characterized by the expression of a set of genes involved in mating that are not expressed in diploids. The mating response to generate diploids is stimulated by the release of small peptide mating[..]

Vegetative yeast cells respond to environmental cues by activating signal transduction pathways that enable them to mount the appropriate physiological response. Each of the cues is dealt with by distinct signaling mechanisms to cause the appropriate response to a given stimulus. In the budding yeast Saccharomyces cerevisae, there are at least five MAP kinase (Mitogen-Activated Protein Kinase) cascades. MAPK cascades are conserved signaling modules that regulate responses to diverse extracellular stimuli, developmental cues and environmental stresses. A MAPK is phosphorylated and activated by a MAPKK (MAPK Kinase), which is activated by an upstream protein kinase, MAPKK kinase. Each pathway is initiated by a distinct upstream regulator and individual MEKK-MEK-MAPK[..]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens.It is characterized by chronic inflammation and synovial hyperplasia that eventually lead to cartilage and bone destruction. Synovial fibroblasts are mesenchymal cells recognized as a key cell population in RA due to their hyperproliferative and hypersensitive properties in the inflammatory milieu and hyperproduction of both inflammatory cytokines and matrix-degrading enzymes.Macrophages are major components in the inflammatory cascade and are also important mediators of joint destruction in RA. Large numbers of macrophages are present in synovial tissue and[..]

Extracellular environmental changes cause different types of stress in all the organisms and can seriously affect the viability of the cells. All cells have signaling pathways required to transmit the stress signals from outside and to develop the response and gene expression changes required to adapt and survive. Cell Integrity Pathway signaling is activated persistently in response to elevated temperatures, Hypo-osmotic shock, mating pheromone etc. The cell integrity pathway  has  sensors that detect changes in the cell wall or membrane caused by different stresses and transmit the stimulus to the MAPK (Mitogen-Activated Protein Kinases) cascade. MAPK cascades generally leads to a change of the cell's size or shape and is also important for processes[..]

The CTLs (Cytotoxic T Lymphocytes), also known as killer T-Cells are produced during cell-mediated immunity designed to remove body cells displaying "foreign" epitope, such as virus-infected cells, cells containing intracellular bacteria, and cancer cells with mutant surface proteins. The CTLs are able to kill these cells by inducing a programmed cell death known as apoptosis (Ref.1).CTLs only respond to foreign antigen when it is presented bound to the MHC-I (Major Histocompatibility Complex Class-I) expressed on the surface of all cells. The CTLs contain granules composed of proteoglycans to which chemokines are complexed. These granules hold pore-forming proteins called perforins and proteolytic enzymes called granzymes in a protected state. When the TCR (T-Cell[..]

Photoreceptors and circadian clocks are univesal mechanisms for sensing and responding to the light environment. In addition to regulating daily activities, photoreceptors and circadian clocks are also involved in the seasonal regulation of processes such as flowering. Circadian rhythms govern many plant processes, including movements of organs such as leaves and petals, stomata opening, stem elongation, sensitivity to light of floral induction, metabolic processes such as respiration and photosynthesis and expression of a large number of different genes. In plants, phototransduction not only sets the phase, but also affects the amplitude and period of circadian rhythms. Members of the phytochrome family of plant photoreceptors, which can exist in two photochemically[..]

Circadian clocks are internal timekeepers that utilize environmental signals to induce cellular events to occur at the most favourable time of day. Circadian clocks in animals, plants, fungi and bacteria have similar characteristic properties and molecular architecture. They have a periodicity of approximately 24 hours, persist in constant conditions and can be reset by environmental time cues such as light and temperature. Although the length of the circadian period is temperature compensated, temperature shifts reset the phase of the oscillator. (Ref.1). Neurospora crassa (N. crassa) a filamentous fungus classified under the Phylum Ascomycota is commonly found in its vegetative state growing as a mycelium of haploid hyphae. The tubular hyphae forms incomplete[..]

The unicellular cyanobacterium Synechococcus elongatus is an obligate photoautotroph and the simplest model organism in circadian biology. Circadian rhythms, regulated by a 24-h biological clock, enable the coordination of biological activity over the course of the day and facilitate adaptation to daily environmental changes in diverse organisms. Unlike the circadian oscillators found in eukaryotic systems, which employ a transcription–translation feedback loop(TTFL), the cyanobacterial core oscillator functions posttranslationally The S. elongatus core oscillator is a posttranslational oscillator (PTO), encoded by transcription factors kaiA, kaiB, and kaiC which regulate the global patterns of gene expression, the timing of cell division and compaction[..]

Apoptosis, necroptosis, and pyroptosis are the three major ways of PCD(programed cell death) following virus infection. Among them, apoptosis is the most extensively investigated PCD during viral infection. Apoptosis elicited by virus infection has both negative and positive influence on viral replication.Apoptosis is triggered by two distinct signaling pathways, namely the intrinsic and extrinsic pathways(Ref.1).The intrinsic apoptotic pathway is elicited by a wide range of intracellular stress conditions, including cytokine deprivation, DNA damage, oxidative stress, cytosolic Ca2+ overload and endoplasmic reticulum stress whereas the extrinsic apoptotic pathway is activated by extracellular stress stimulation that is sensed and triggered through activation of death[..]

Our bones get more brittle with increasing age, and to add insult to injury, the most effective therapy for another problem that is associated with getting older, rheumatoid arthritis, often adds to the problem by causing bone resorption. The Glucocorticoid steroids, are the best available anti-inflammatories, and are used widely in the treatment of arthritis, as well as other inflammatory conditions such as dermatitis and autoimmune diseases. The Glucocorticoids, secreted by the Adrenal Cortex are powerful anti-inflammatory compounds due to their ability to inhibit all stages of the inflammatory response, from redness to wound healing to cell proliferation (Ref.1). They are powerful anti-inflammatory compounds that have the ability to inhibit all stages of the[..]

Cell cycle arrest in response to DNA damage is an important mechanism for maintaining genomic integrity. This cell cycle arrest provides time for DNA repair to prevent replication or segregation of damaged DNA. Induction of growth arrest by DNA damage occurs mainly through the activation of checkpoint pathways that delay cell cycle progression at G1, S, and G2 (Ref.1 and 2).In vertebrate cells, the commitment to complete a round of mitotic division takes place during the initial phase of the cell cycle (G1), at a stage called the restriction (R) point, preceding the onset of DNA synthesis (S-phase).The primary G1/S cell cycle checkpoint controls the commitment of eukaryotic cells to transition through the G1 phase to enter into the DNA synthesis S phase. Two cell cycle[..]