Join queries optimization in the distributed databases using a hybrid multi-objective algorithm

Cluster Computing - In the distributed database systems, the relations needed by a query can be kept in several locations. This process significantly increases potential corresponding Query...     

Metronidazole aryloxy,carboxy and azole derivatives: Synthesis,anti-tumor activity,QSAR, molecular docking and dynamics studies

A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC₅₀s?less than?100?µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.     

Enhanced h6h transcript level,antioxidant activity and tropane alkaloid production in Hyoscyamus reticulatus L. hairy roots elicited by acetylsalicylic acid

Hyoscyamine (Hyos) and scopolamine (SCP) are drugs widely used as antimuscarinic to treat diseases such as Parkinson’s or to calm schizoid patients. In this study, with the aim of enhancing tropane alkaloid production in H. reticulatus hairy root cultures, the effects of the signalling molecule acetylsalicylic acid (ASA) were investigated at different concentrations (0, 0.01, 0.1 and 1 mM) and inoculation times (24 and 48 h). As well as reducing biomass production, ASA treatment significantly enhanced the activity of catalase, guaiacol peroxidase and ascorbate peroxidase (p < 0.01), which was highest at 48 h of exposure to 1 mM of ASA. The highest accumulation of Hyos and SCP (1.6- and 3.5-fold more than in the control, respectively) was obtained at 24 h of exposure to 0.1 mM ASA. Additionally, semi-quantitative RT-PCR analysis showed an increased expression of the hyoscyamine-6-beta-hydroxylase (h6h) gene, involved in the last Hyos and SCP biosynthetic step, which correlated with the enhanced level of Hyos and SCP production under ASA elicitation. Our findings suggest that ASA, by stimulating the expression of key biosynthetic genes and enzymes, can be applied to increase commercial tropane alkaloid production in a H. reticulatus hairy root system.     

A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of an obligate intracellular lifestyle

We present the draft genome for the Rickettsia endosymbiont of Ixodes scapularis (REIS), a symbiont of the deer tick vector of Lyme disease in North America. Among Rickettsia species (Alphaproteobacteria: Rickettsiales), REIS has the largest genome sequenced to date (>2 Mb) and contains 2,309 genes across the chromosome and four plasmids (pREIS1 to pREIS4). The most remarkable finding within the REIS genome is the extraordinary proliferation of mobile genetic elements (MGEs), which contributes to a limited synteny with other Rickettsia genomes. In particular, an integrative conjugative element named RAGE (for Rickettsiales amplified genetic element), previously identified in scrub typhus rickettsiae (Orientia tsutsugamushi) genomes, is present on both the REIS chromosome and plasmids. Unlike the pseudogene-laden RAGEs of O. tsutsugamushi, REIS encodes nine conserved RAGEs that include F-like type IV secretion systems similar to that of the tra genes encoded in the Rickettsia bellii and R. massiliae genomes. An unparalleled abundance of encoded transposases (>650) relative to genome size, together with the RAGEs and other MGEs, comprise ~35% of the total genome, making REIS one of the most plastic and repetitive bacterial genomes sequenced to date. We present evidence that conserved rickettsial genes associated with an intracellular lifestyle were acquired via MGEs, especially the RAGE, through a continuum of genomic invasions. Robust phylogeny estimation suggests REIS is ancestral to the virulent spotted fever group of rickettsiae. As REIS is not known to invade vertebrate cells and has no known pathogenic effects on I. scapularis, its genome sequence provides insight on the origin of mechanisms of rickettsial pathogenicity.     

Determining the mode of action of bioactive compounds

Matching bioactive molecules with molecular targets is key to understanding their modes of action (MOA). Moving beyond the mere discovery of drugs, investigators are now just beginning to integrate both biochemical and chemical-genetic approaches for MOA studies. Beginning with simple screens for changes in cell phenotype upon drug treatment, drug bioactivity has been traditionally explored with affinity chromatography, radiolabeling, and cell-based affinity tagging procedures. However, such approaches can present an oversimplified view of MOA, especially in light of the recent realization of the extent of polypharmacology and the unexpected complexity of drug-target interactions. With the advent of more sophisticated tools for genetic manipulation, a flood of powerful techniques has been used to create characteristic drug MOA 'fingerprints'. In particular, whole genome expression profiling and deletion and overexpression libraries have greatly enhanced our understanding of bioactive compounds in vivo. Here we highlight challenges and advances in studying bioactive compound-target interactions.     

Learning chronobiology by improving wikipedia

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.     

p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65

The stress-activated c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein (MAP) kinase (p38) regulate apoptosis induced by several forms of cellular insults. Potential targets for these kinases include members of the Bcl-2 family proteins, which mediate apoptosis generated through the mitochondria-initiated, intrinsic cell death pathway. Indeed, the activities of several Bcl-2 family proteins, both pro- and anti-apoptotic, are controlled by JNK phosphorylation. For example, the pro-apoptotic activity of Bim(EL), a member of the Bcl-2 family, is stimulated by JNK phosphorylation at Ser-65. In contrast, there is no reported evidence that p38-induced apoptosis is due to direct phosphorylation of Bcl-2 family proteins. Here we report evidence that sodium arsenite-induced apoptosis in PC12 cells may be due to direct phosphorylation of Bim(EL) at Ser-65 by p38. This conclusion is supported by data showing that ectopic expression of a wild type, but not a non-phosphorylatable S65A mutant of Bim(EL), potentiates sodium arsenite-induced apoptosis and by experiments showing direct phosphorylation of Bim(EL) at Ser-65 by p38 in vitro. Furthermore, sodium arsenite induced Bim(EL) phosphorylation at Ser-65, which was blocked by p38 inhibition. This study provides the first example whereby p38 induces apoptosis by phosphorylating a member of the Bcl-2 family and illustrates that phosphorylation of Bim(EL) on Ser-65 may be a common regulatory point for cell death induced by both JNK and p38 pathways.