ISRN molecular biology最新文献

Macroautophagy (hereafter autophagy) is currently one of the areas of medical life sciences attracting a great interest because of its pathological implications and therapy potentials. The discovery of the autophagy-related genes (ATGs) has been the key event in this research field because their study has led to the acquisition of new knowledge about the mechanism of this transport pathway. In addition, the investigation of these genes in numerous model systems has revealed the central role that autophagy plays in maintaining the cell homeostasis. This process carries out numerous physiological functions, some of which were unpredicted and thus surprising. Here, we will review some of the questions about the mechanism and function of autophagy that still remain unanswered, and new ones that have emerged from the recent discoveries.

The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβ family members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβ signaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβ signaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβ are often lost. TGFβ signaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβ signaling pathway without affecting its tumor suppressive effects.

In the last decade, there has been an explosion of publications on the assembly of β-barrel outer membrane proteins (OMPs), which carry out diverse cellular functions, including solute transport, protein secretion, and assembly of protein and lipid components of the outer membrane. Of the three outer membrane model systems-Gram-negative bacteria, mitochondria and chloroplasts-research on bacterial and mitochondrial systems has so far led the way in dissecting the β-barrel OMP assembly pathways. Many exciting discoveries have been made, including the identification of β-barrel OMP assembly machineries in bacteria and mitochondria, and potentially the core assembly component in chloroplasts. The atomic structures of all five components of the bacterial β-barrel assembly machinery (BAM) complex, except the β-barrel domain of the core BamA protein, have been solved. Structures reveal that these proteins contain domains/motifs known to facilitate protein-protein interactions, which are at the heart of the assembly pathways. While structural information has been valuable, most of our current understanding of the β-barrel OMP assembly pathways has come from genetic, molecular biology, and biochemical analyses. This paper provides a comparative account of the β-barrel OMP assembly pathways in Gram-negative bacteria, mitochondria, and chloroplasts.

Mangroves and salt marsh species are known to synthesize a wide spectrum of polysaccharides and polyphenols including flavonoids and other secondary metabolites which interfere with the extraction of pure genomic DNA. Although a plethora of plant DNA isolation protocols exist, extracting DNA from mangroves and salt marsh species is a challenging task. This study describes a rapid and reliable cetyl trimethylammonium bromide (CTAB) protocol suited specifically for extracting DNA from plants which are rich in polysaccharides and secondary metabolites, and the protocol also excludes the use of expensive liquid nitrogen and toxic phenols. Purity of extracted DNA was excellent as evident by A260/A280 ratio ranging from 1.78 to 1.84 and A260/A230 ratio was >2, which also suggested that the preparations were sufficiently free of proteins and polyphenolics/polysaccharide compounds. DNA concentration ranged from 8.8 to 9.9 μg μL(-1). The extracted DNA was amenable to RAPD, restriction digestion, and PCR amplification of plant barcode genes (matK and rbcl). The optimized method is suitable for both dry and fresh leaves. The success of this method in obtaining high-quality genomic DNA demonstrated the broad applicability of this method.

Voltage-gated L-type Cav1.2 calcium channels couple membrane depolarization to transient increase in cytoplasmic free Ca(2+) concentration that initiates a number of essential cellular functions including cardiac and vascular muscle contraction, gene expression, neuronal plasticity, and exocytosis. Inactivation or spontaneous termination of the calcium current through Cav1.2 is a critical step in regulation of these processes. The pathophysiological significance of this process is manifested in hypertension, heart failure, arrhythmia, and a number of other diseases where acceleration of the calcium current decay should present a benefit function. The central issue of this paper is the inactivation of the Cav1.2 calcium channel mediated by multiple determinants.

GLUT4 has long been known to be an insulin responsive glucose transporter. Regulation of GLUT4 has been a major focus of research on the cause and prevention of type 2 diabetes. Understanding how insulin signaling alters the intracellular trafficking of GLUT4 as well as understanding the fate of glucose transported into the cell by GLUT4 will be critically important for seeking solutions to the current rise in diabetes and metabolic disease.

Antimicrobial peptides are humoral innate immune components of molluscs that provide protection against pathogenic microorganisms. Among these, histone-H2A-derived antimicrobial peptides are known to actively participate in host defense responses of molluscs. Present study deals with identification of putative antimicrobial sequences from the histone-H2A of back-water oyster Crassostrea madrasensis, rock oyster Saccostrea cucullata, grey clam Meretrix casta, fig shell Ficus gracilis, and ribbon bullia Bullia vittata. A 75 bp fragment encoding 25 amino acid residues was amplified from cDNA of these five bivalves and was named "Molluskin." The 25 amino acid peptide exhibited high similarity to previously reported histone-H2A-derived AMPs from invertebrates indicating the presence of an antimicrobial sequence motif. Physicochemical properties of the peptides are in agreement with the characteristic features of antimicrobial peptides, indicating their potential role in innate immunity of molluscs.

Nucleosome positioning is not only related to genomic DNA compaction but also to other biological functions. After the chromatin is digested by micrococcal nuclease, nucleosomal (nucleosome-bound) DNA fragments can be sequenced and mapped on the genomic DNA sequence. Due to the development of modern DNA sequencing technology, genome-wide nucleosome mapping has been performed in a wide range of eukaryotic species. Comparative analyses of the nucleosome positions have revealed that the nucleosome is more frequently formed in exonic than intronic regions, and that most of transcription start and translation (or transcription) end sites are located in nucleosome linker DNA regions, indicating that nucleosome positioning influences transcription initiation, transcription termination, and gene splicing. In addition, nucleosomal DNA contains guanine and cytosine (G + C)-rich sequences and a high level of cytosine methylation. Thus, the nucleosome positioning system has been conserved during eukaryotic evolution.

Regulation of microtubule dynamics depends on stochastic balance between polymerization and severing process which lead to differential spatiotemporal abundance and distribution of microtubules during cell development, differentiation, and morphogenesis. Microtubule severing by a conserved AAA family protein Katanin has emerged as an important microtubule architecture modulating process in cellular functions like division, migration, shaping and so on. Regulated by several factors, Katanin manifests connective crosstalks in network motifs in regulation of anisotropic severing pattern of microtubule protofilaments in cell type and stage dependent way. Mechanisms of structural disintegration of microtubules by Katanin involve heterogeneous mechanochemical processes and sensitivity of microtubules to Katanin plays significant roles in mitosis/meiosis, neurogenesis, cilia/flagella formation, cell wall development and so on. Deregulated and uncoordinated expression of Katanin has been shown to have implications in pathophysiological conditions. In this paper, we highlight mechanistic models and regulations of microtubule severing by Katanin in context of structure and various functions of Katanin in different organisms.

Depletion of YhcB, an inner membrane protein of Escherichia coli, inhibited the growth of rodZ deletion mutant showing that the loss of both YhcB and RodZ is synthetically lethal. Furthermore, YhcB was demonstrated to interact with RodZ as well as several other proteins involved in cell shape maintenance and an inner membrane protein YciS of unknown function, using bacterial two-hybrid system. These observations seem to indicate that YhcB is involved in the biogenesis of cell envelope and the maintenance of cell shape together with RodZ.