Frontiers in Bioscience : a Journal and Virtual Library

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone lesions and production of a paraprotein. B-lymphocyte stimulator (BLyS) and its receptor (BAFFR) were highly expressed on peripheral blood and bone marrow B cells in MM patients as compared to those with monoclonal gammopathy of unknown significance (MGUS) and healthy donors. Serum BLyS levels in MM patients were significantly higher than those in MGUS patients and healthy controls. BLyS expression was increased in bone marrow specimens from MM patients as ascertained by immunofluorescence...

Thoracic aortic aneurysm and dissections (TAADs) are associated with both high mortality and medical expense. Poor outcomes are preventable by surgical repair; however, identifying individuals at-risk is difficult. Researchers are scanning the human genome to characterize the genetic determinants of TAADs by identifying chromosomal regions, gene mutations, single nucleotide polymorphism (SNP), genomic copy number variants and micro-RNA variants, with the purpose of analyzing the risk of TAADs associated with these predisposing genes...

Naturally occurring protein-based materials have been found that function as critical components in biomechanical response, fibers and adhesives. A relatively small but growing number of recombinant protein-based materials that mimic the desired features of their natural sources, such as collagens, elastins and silks, are considered as an alternative to conventional synthetic polymers. Advances in genetic engineering have facilitated the synthesis of repetitive protein polymers with precise control of molecular weights which are designed by using synthetic genes encoding tandem repeats of oligopeptide originating from a modular domain of natural proteins...

The tumor susceptibility gene 101 (TSG101) encodes a multidomain protein that contains a UEV (ubiquitin e2 variant) domain at is N-terminus and a putative DNA-binding motif at its C-terminus. In addition to being a bona fide component of the ESCRT (endosomal sorting complexes required for transport) complex 1 and playing a critical role in endosomal sorting and trafficking, TSG101 has also been implicated in an array of cellular functions including, cytokinesis, protein ubiquitination, transcriptional regulation, cell cycle and proliferation, as well as viral budding...

Motor proteins are enzymes that accomplish mechanical work in a wide variety of biological processes. In this review we focus on bulk and single molecule methods to study how motor proteins function. We discuss in detail the analysis of the motor protein DnaB, a hexameric helicase that unwinds DNA at a replication fork in Gram-negative bacteria. Bulk and single-molecule studies have complemented one another to arrive at a comprehensive mechanistic view of how DnaB unwinds double-stranded DNA.

Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper-middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity...

Archaea occupy a considerable diversity of niches ranging from extreme of pH, salinity to temperature that cannot be tolerated by other forms of life. There is an increasing consciousness that they have a key role both on the biogeochemical cycling of elements and in the bioremediation of polluted habitat. A greater understanding of metal homeostasis and resistance to toxic compounds in this life domain is required to design new strategies for the bioremediation of contaminated sites. This review describes the strategies developed by Archaea to transform xenobiotic compounds and metal ions present in the environment...

Breast cancer is a major cause of cancer death in women in the world. Triple-negative breast cancers, which accounts for 10-20% of all mammary tumours, are characterised by an aggressive phenotype, are often found in younger women and have been associated with poor prognosis. Obesity increases the risk for triple-negative breast cancer occurrence. Because triple-negative breast cancer patients are unresponsive to current targeted therapies and other treatment options are only partially effective, new pharmacological approaches are warranted...

Oxidative stress may play a role in the pathogenesis of age-related macular degeneration (AMD). In this study we examined the association between AMD risk and polymorphisms of genes encoding enzymes involved in the generation and removal of iron-mediated oxidation: NQO1 (609C> T, rs1800566), NOS3 (894G>T, rs1799983) and NFE2L2 (28312647A>G, rs6726395). We found that the G/G genotype of the rs6726395 polymorphism was associated with a decreased risk of AMD wet form (OR 0.44) and on the other hand the T allele of the rs1799983 polymorphism increased such risk (OR 1...

The chance to selectively intervene and stop the development of any gene-dependent disease in different organs and pathologies makes siRNA an ideal therapeutic agent. However, serious issues should be addressed before the real therapeutic use of siRNA. The poor pharmacokinetic properties of siRNA, its short half-life, its low in vivo stability, its fast elimination by kidney filtration and its low transfection efficiency complicate the use of siRNA as a therapeutic molecule. In this review, we will describe the latest and most advanced approaches and strategies undertaken to address these limitations and improve siRNA delivery and its gene silencing efficacy as well as the prospects for its therapeutic applications...

Cytochrome c oxidase (COX) terminates the respiratory chain in mitochondria and in plasmatic membrane of many aerobic bacteria. The enzyme reduces dioxygen molecule into water and the reaction is accompanied with generation of transmembrane difference of electric potentials. The energy conservation by COX is based on the vectorial organization of the chemical reaction due to substrate protons transfer from the negative phase into the active site to meet the electrons, coming from opposite side of the membrane...

While there is a rather large amount of data from pharmacological and anatomical studies of the murine locomotor CPG network, comprehensive information regarding the cellular and functional properties of the neuronal populations is lacking. Here we describe concepts arising from genetic studies of the locomotor network with a focus on commissural interneurons regulating left-right coordination. In particular, this involves several families of axon guidance molecules relevant for midline crossing. We also describe recent advances within the field of neural circuit analysis, including imaging, genetic inactivation and optogenetic strategies, which are applicable to locomotor circuits...

Mounting body of evidence indicates that the disruption of epithelial tight junctions and resulting loss of barrier function play a crucial role in the pathogenesis of a variety of gastrointestinal, hepatic, pulmonary, kidney and ocular diseases. Increased production of inflammatory mediators such as cytokines and reactive oxygen species disrupt the epithelial and endothelial barrier function by destabilizing tight junctions. Oxidative stress induced by various reactive oxygen species such as hydrogen peroxide, nitric oxide, peroxynitrite and hypochlorous acid disrupt the epithelial and endothelial tight junctions in various tissues...

This study is to examine our hypothesis that CD4+CD25(high)Foxp3+ regulatory T cells (Tregs) have an interleukin-2 (IL-2) withdrawal-triggered apoptosis pathway, and modulation of Treg apoptosis pathway affects development of vascular inflammation. We found that pro-apoptotic protein Bax upregulation in Tregs is induced by IL-2 withdrawal. Treg apoptosis induced by IL-2 withdrawal is inhibited by a Bax inhibitor, suggesting that highly expressed Bax is functional. To define the role of upregulated Bax in Treg apoptosis, we established a Tregs-specific Bax transgenic mouse model...

Proteins that combine PML NBs (ND10) can be divided into two groups: "transient" (that accumulate at PML NBs upon over-expression, interferon-induced up-regulation, block of proteosomal degradation, environmental stress or viral infection) and "constitutive" that co-localize with PML in the majority of cultured cells. One of the few "constitutive" components of PML NBs is the death domain-associated protein Daxx. While PML NBs are the most obvious depositories of Daxx, there are multiple alternative localization of this protein in the nucleus and cytoplasm, suggesting differential functionality of Daxx at different cellular compartments and stages of the cell cycle...

A major goal in the field of aging research is to identify molecular mechanisms of aging at the cellular level, which are anticipated to form the basis for the development of age-associated dysfunctions and diseases in human beings. Recent progress in research into model organisms of aging has allowed determining precise molecular mechanisms and genetic determinants of the aging process, which appear to be conserved in evolution and some of which apply to human aging as well. The consortium of the authors focuses on aging mechanisms at the cellular level, and exploits the potential of genetic analyses in lower eukaryotic model organisms for a better understanding of regulatory pathways implicated in aging processes...

This study focused on the effect of electro-stimulation of fastigial nucleus on the expression of NgR and on axonal regeneration after focal cerebral ischemia-reperfusion in rats. Cerebral ischemia and reperfusion was induced by nylon monofilament. Ninety-six male SD rats were randomly divided into sham group and ischemic insult groups at 12 hours, 24 hours, and 1 to 3 weeks after cerebral ischemia-reperfusion. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the changes of NgR mRNA expression...

Our current understanding of epithelial-mesenchymal transition (EMT) in the setting of tissue fibrosis is largely based on pioneering studies in the kidney. Evidence is emerging that EMT is a key component of chronic kidney disease, contributing to both destruction of the tubular epithelial compartment and accumulation of interstitial fibroblasts. While knowledge regarding EMT was previously based on experimental rodent studies, in recent years the evolving evidence demonstrates a role for EMT in human kidney diseases with chronic fibrosis...

Understanding the molecular mechanisms underlying the ageing process may provide the best strategy for addressing the challenges posed by ageing populations worldwide. One theory proposing such molecular mechanisms was formulated 50 years ago. Harman et al. suggested that ageing might be mediated by macromolecular damage through reactions involving reactive oxygen species (ROS). Today, a version of the free radical theory of ageing, focusing on mitochondria as source as well as target of ROS, is one of the most popular theories of ageing...

The tumor microenvironment is a mixture of extracellular matrix molecules, tumor cells, endothelial cells, fibroblasts and immune cells. Tumor growth and metastasis formation are dependent on the growth of blood vessels into the tumor mass. The tumor microenvironment contributes to this pathological angiogenic process. The extracellular matrix and basement membranes are a source for endogenous angiogenesis inhibitors, such as endostatin. On the other hand, many extracellular matrix molecules can promote angiogenesis by stabilizing blood vessels and sequestering pro-angiogenic growth factors...