Renewed studies of chronic infection have shifted the focus from single pathogens to multi-microbial communities as culture-independent techniques reveal complex consortia of microbes associated with chronic disease. Despite a general acceptance that some chronic diseases are caused by mixed microbial communities, areas of research exploring community interactions as they relate to the alteration of virulence are still in the early stages. Members of the NIH Human Microbiome Project have been actively characterizing the microbial communities of the skin, nasal, oral, gastrointestinal, and urogenital cavities of healthy adults. Concomitantly, several independent studies have begun to characterize the oral, nasal, sinus, upper and lower respiratory microbiomes in healthy and diseased human tissue. The interactions among the members of these polymicrobial communities have not been thoroughly explored and it is clear there is a need to identify the functional interactions that drive population-level virulence if new therapeutic approaches to chronic disease are to be developed. For example, multiple studies have examined the role of quorum sensing (QS) in microbial virulence, and QS antagonists are being developed and tested as novel therapeutics. Other potential targets include the Gram-negative type III signaling system (T3SS), type IV pili, and two component regulatory systems (TCRS). Initial results from these studies indicate limited efficacy
Influenza A virus is one of the major pathogens that pose a large threat to human health worldwide and has caused pandemics. Influenza A virus is the
Endogenous small RNAs (miRNAs and siRNAs) regulate gene expression in diverse biological processes. Research with the
Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl-D-aspartate (NMDA) receptors. Conversely, normal physiological brain function and neuronal survival require adequate activation of NMDA receptors. Studies have revealed that NMDA receptor-induced neuronal death or survival is mediated through distinct subset of NMDA receptors triggering different intracellular signaling pathways. Here we discuss recent advances in the characterization of NMDA receptors in neuronal protection, emphasizing subunit-specific role, which contributes to temporal-spatial distribution, subcellular localization and diverse channel properties of NMDA receptors.
Epigenetics has been becoming a hot topic in recent years. It can be mechanisms that regulate gene expression without changing DNA base sequence. In plants epigenetic regulation has been implicated to be a very important phenomenon and mechanism for the regulation of responses to environmental stresses. Environmental signals induce various epigenetic modifications in the genome, and these epigenetic modifications might likely be inherited to the next generation that behaves with enhanced ability to tolerate stresses. This review highlights recent advances in the study of epigenetics in plant stress responses.
Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in the United States. Three quarters of patients diagnosed with colorectal cancer will have early stage disease and despite surgical resection for curative intent, approximately 20%–25% of patients will recur with their disease within five years. The other 25% will present with advanced or metastatic disease and clinicians are faced with the challenge of choosing the most appropriate therapy for individual patients. Despite multiple treatment options which are now available and concomitant improvements in survival, advanced colorectal cancer remains universally fatal. The challenge for clinicians is to identify prognostic and predictive biomarkers that can assist in tailoring available treatments for an individual patient to improve clinical outcomes. This review will summarize current and future biomarkers in colorectal cancer and discuss their utility in managing patient care.
The information provided by completely sequenced genomes of methanogens can yield insights into a deeper molecular understanding of evolutionary mechanisms. This review describes the advantages of using metabolic pathways to clarify evolutionary correlation of methanogens with archaea and prokaryotes. Metabolic trees can be used to highlight similarities in metabolic networks related to the biology of methanogens. Metabolic genes are among the most modular in the cell and their genes are expected to travel laterally, even in recent evolution. Phylogenetic analysis of protein superfamilies provides a perspective on the evolutionary history of some key metabolic modules of methanogens. Phage-related genes from distantly related organisms typically invade methanogens by horizontal gene transfer. Metabolic modules in methanogenesis are phylogenetically aligned in closely related methanogens. Reverse order reactions of methanogenesis are achieved in methylotrophic methanogens using metabolic and structural modules of key enzymes. A significant evolutionary process is thought to couple the utilization of heavy metal ions with energetic metabolism in methanogens. Over 30 of methanogens genomes have been sequenced to date, and a variety of databases are being developed that will provide for genome annotation and phylogenomic analysis of methanogens. Into the context of the evolutionary hypothesis, the integration of metabolomic and proteomic data into large-scale mathematical models holds promise for fostering rational strategies for strain improvement.
The Hedgehog (Hh) family of secreted proteins plays essential roles in the development of a wide variety of animal species and underlies multiple human birth defects and cancers. To ensure the proper range of signaling, the Hh proteins are modified with lipids, assembled into water-soluble multimers, and interact with multiple cell surface proteins. In the target cells, a largely conserved intracellular signal transduction pathway, from the cell surface receptor Patched to the Glioma-associated oncogene homolog (Gli) family of transcription factors, mediates the transcriptional responses from fruit flies to mammals. A significant divergence between vertebrates and insects is the vertebrate-specific requirement of cilia for Hh signal transduction and Gli protein activation. Finally, transcription-independent cellular responses to Hh have been described in certain developmental processes. With clinical trial underway to treat Hh-related diseases, more work is urgently needed to reach a more comprehensive understanding of the molecular mechanisms underlying the regulation of Hh signaling in development and diseases.