ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig’s disease, is a devastating neurodegenerative disorder, which is characterized by the selective degeneration of upper and lower motor neurons, the large nerve cells connecting the brain to the spinal cord and from the spinal cord to muscles, which control muscle movement. The loss of motor neurons leads to progressive atrophy of skeletal muscles. ALS is a relentless disease that manifests as progressive decline in muscular function resulting in eventual paralysis, speech deficits and, ultimately, death due to respiratory failure in the majority of ALS patients within 2 to 5 years of clinical onset. In spite of its notoriety, the mechanisms underlying ALS remain obscure and therapies with long-term[..]

The translocation of proteins from one compartment to another is an essential feature of cellular life. The proper functioning of extracytoplasmic proteins requires their export to, and productive folding in, the correct cellular compartment.  Gram-negative bacteria secrete a wide range of proteins whose function includes biogenesis of organelles, such as Pili and flagella; nutrient acquisition; virulence; and efflux of drugs and other toxins. Export of these proteins to the bacterial surface involves transport across the IM (Inner Membrane), Periplasm, and OM (Outer Membrane) of the cell envelope. All proteins in Escherichia coli are initially synthesized in the cytoplasm then follow a pathway that depends upon their ultimate cellular destination. Many proteins[..]

Teeth develop as ectodermal appendages in vertebrate embryos, and their early development resembles morphologically as well as molecularly other organs such as Hairs and Glands. Interactions between the Ectoderm and underlying Mesenchyme constitute a central mechanism regulating the morphogenesis of all these organs. Central features of Tooth morphogenesis are the formation of the Epithelial Placode, the budding of the Epithelium, the condensation of Mesenchyme around the bud, and the folding and growth of the Epithelium generating the shape of the Tooth Crown. The mineralized structures characteristic for Teeth, which is, Dentin and Enamel, are formed by specialized cells, the Odontoblasts and Ameloblasts differentiating from the Mesenchyme and Epithelium,[..]

The cell membranes do not simply serve as barriers to separate the inside of the cell from the outside or to delineate different intracellular compartments. These membranes also serve as a platform for cell signaling by allowing specific sets of proteins to interact. Phospholipids are major structural constituents of the cell membranes. In the cell membranes of neurons, the two most prevalent Phospholipids include PC (Phosphatidylcholine) and PS (Phosphatidylserine). When cell membranes are stimulated by cell signaling activity, enzymes (called Phospholipases) free lipid messengers from these reservoirs. The lipid messengers then regulate and interact with other signaling cascades to contribute to the development, differentiation, function protection, and repair of the[..]

Cellular Lipid homeostasis in mammalian cells is regulated through the end-product feedback regulation of Lipid synthesis by a family of membrane-bound transcription factors designated SREBPs (Sterol Regulatory Element–Binding Proteins) that control the flux of cellular metabolites into the major Lipid pathways. The mammalian cell continuously adjusts its Sterol content by regulating levels of key Sterol synthetic enzymes and levels of Lipoprotein receptors that mediate uptake of Cholesterol-laden particles. Control is brought about by SREBPs, which monitor the Sterol-regulated transcription and directly activate the expression of more than 30 relevant genes dedicated to the synthesis and uptake of Cholesterol, Fatty Acids, Triglycerides, and Phospholipids, as well[..]

As research into tumour immunology continues at an incredible pace, a considerable amount of work is aimed at exploring the mechanisms that underlie the immunological recognition and elimination of cancer and the downstream consequences of these processes. The capacity of the immune system for recognition is not limited solely to the classic models of self versus pathogen or self versus non-self but encompasses the more-subtle differences that exist between self and transformed self. This conclusion provides the argument for reconsidering the largely discarded hypothesis of cancer immunosurveillance. Immune system attempts to constrain tumour growth, but sometimes tumour cells might escape or attenuate this immune pressure, similar to the way in which these cells[..]

Cell-fate decisions are controlled typically by conserved receptors that interact with co-evolved ligands. Therefore, the lineage-specific differentiation of immature CD4+CD8+ T cells into CD4+ or CD8+ mature T cells is unusual in that it is regulated by clonally expressed, somatically generated T-cell receptors (TCRs) of unpredictable fine specificity. Each mature T cell generally retains expression of the co-receptor molecule (CD4 or CD8) that has an MHC-binding property that matches that of its TCR. Two models were proposed initially to explain this remarkable outcome--'instruction' of lineage choice by initial signalling events or 'selection' after a stochastic fate decision that limits further development to cells with coordinated TCR and co-receptor[..]

MDSCs (Myeloid-Derived Suppressor Cells) are recently been recognized as critical mediators of tumor progression in numerous solid tumours through their inhibition of tumor-specific immune responses. These cells are increased in numerous pathologic conditions, including infections, inflammatory diseases, graft-versus-host disease, traumatic stress, and neoplastic diseases. MDSCs inhibit not only activation of T cells by anti-CD3 and super antigen, but also antigen-specific CD4+ and CD8+ T-cell responses. The mechanisms of MDSC immunosuppression are diverse, it includes up-regulation of ROS (Reactive Oxygen Species), NO (Nitric Oxide), and L-Arginine metabolism. It also facilitates tumour-induced immune suppression and tumour progression by inducing the[..]

Immune cells in the tumour microenvironment not only fail to mount an effective anti-tumour immune response, but also interact intimately with the transformed cells to promote oncogenesis actively.  STAT (Signal Transducer and Activator of Transcription) proteins act as a mediator of cytokine receptor signaling. This protein plays a role in transmitting the signals of growth factor receptors and is both cytoplasmic signaling molecules and nuclear transcription factors that activate diverse genes. In normal cells, STAT activation is transient and tightly regulated. While STAT3 (Signal Transducer and Activator of Transcription 3)   acts as a point of convergence for numerous oncogenic signalling pathways, and constitutively remain active both in tumour[..]

The immune system has three primary roles in the prevention of tumors. First, the immune system can protect the host from virus-induced tumors by eliminating or suppressing viral infections. Second, the timely elimination of pathogens and prompt resolution of inflammation can prevent the establishment of an inflammatory environment conducive to tumorigenesis. Third, the immune system can specifically identify and eliminate tumor cells on the basis of their expression of tumor-specific antigens or molecules induced by cellular stress. The evolution of the cancer immunoediting concept from the older and perhaps more controversial ‘cancer immunosurveillance’ hypothesis has helped interpret the predictive and prognostic significance of immune infiltrates into[..]

Cancer immunotherapy attempts to exploit the exquisite power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is clearly capable of recognizing and eliminating tumour cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for immunotherapy is to use advances in cellular and molecular immunology to develop strategies that effectively and safely augment antitumour responses. By contrast, the immune system has evolved strategies, largely in response to infections, to efficiently search for and specifically destroy diseased targets. Advances in cellular and molecular immunology have provides enormous insights in[..]

Tumour cells characteristically provides their own growth signals, and ignore growth-inhibitory signals, avoid cell death, replicate without limits, sustain angiogenesis, and invade tissues through basement membranes and capillary walls. Whereas cancer immunosurveillance predicts that the immune system can recognize precursors of cancer and, in most cases, destroy these precursors before they become clinically apparent. But sometimes tumour cells use to escape these innate and adaptive immune responses by immunoselection (that is, selection of non-immunogenic tumour-cell variants, a process that is also known as immunoediting) or by immunosubversion (that is, active suppression of the immune response) and heads towards a difficult situation which is refer as cancer.[..]