Increasing The Odds Of Hit Iidentification By Screening Against Receptor Homologs

Increasing the odds of hit identification in screening is of significance for drug discovery. The odds for finding a hit are closely related either to the diversity of libraries or to the availability of focused libraries. There are no truly diverse libraries and it is difficult to design focused libraries without sufficient information. Hence it is helpful to consider alternative approaches that can enhance the odds using existing libraries. Multiple members of a protein family have been considered collectively in inhibitor design, on the basis of the correlation between protein families and ligands derived from specific compound classes. Such a correlation has been exploited in various drug discovery studies and a general receptor-homolog-based screening scheme may be devised. The feasibility of such a scheme in enhancing the odds of hit identification is discussed.Singapore-MIT Alliance (SMA

Identification of the forensically important flies (Diptera: Muscidae) based on cytochrome oxidase subunit I (COI) gene in China

Accurate species identification is a crucial step in forensic entomology, as the insect collected on a corpse can provide useful information for estimation of postmortem interval (PMI). However, morphological distinction may on occasion be impossible to the adult flies and nymphs of the same genus. DNA-based method can be used as a supplemental means of morphological method. In this study, 31 forensically important Muscidae flies were collected from 15 locations in 11 provinces of China, and a 272 base pair region of the mitochondrial cytochrome oxidase subunit I (COI) gene was sequenced. The monophyletic branches of the phylogenetic tree revealed that this marker is suitable for discrimination between these five species of four genera of Muscidae. The genetic variations found on COI can be applied not only to identify the forensically important species, but also to understand the taxonomic positions of the sarcophagine species. In addition, this research will be instrumental for implementation of the Chinese Muscidae database.Keywords: Forensic science, forensic entomology, Muscidae, cytochrome oxidase subunit I (COI), species identificatio

Identification of forensically significant beetles (Coleoptera: Staphylinoidae) based on COI gene in China

_________________________________________________________________________________________ Abstract: Accurate and fast identification of insect species is an initial and crucial step of using entomological evidence in forensic cases. Beetles of Coleoptera usually take large parts of taxonomic composition of the carrion-arthropod community and have important meaning for the estimation of postmortem interval (PMI). Traditional morphological taxonomy of beetles poses a great challenge for forensic investigators without entomological background. A cytochrome oxidase subunits one (COI) sequence on mitochondrial DNA with 816-bp length was studied for molecular identification of forensic significant beetles. Six beetle species in superfamily Staphylinoidae collected from four locations in China were sampled. All species were successfully separated with high support value, which indicated this partial COI fragment was sufficient for distinguishing these beetles. Further step utilization of COI fragment in identification of forensically important beetles was also discussed. Key Words: forensic entomology; coleoptera; staphylinoidae; specie identification; cytochrome oxidase subunits one F orensic entomology is the study of insects and other arthropods, being used to solve litigation in civil and criminal cases. The value of forensic entomology for postmortem interval (PMI) in practical forensic work has been well demonstrated in many case studies Actually, the duration of early instars on carrion is generally longer in Coleoptera than that of Diptera The potential of beetles in investigation of forensic case and research work has been discussed in a few articles published recently, usually including beetle species from family Staphylinidae (rove beetles

MiRNA-Directed Regulation of VEGF and Other Angiogenic Factors under Hypoxia

MicroRNAs (miRNAs) are a class of 20–24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle). We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false positive miRNAs might be useful strategies in the avoidance of unwanted cross-action among genes targeted by miRNAs with multiple targets

Bubble in the Whale: Identifying the Optical Counterparts and Extended Nebula for the Ultraluminous X-ray Sources in NGC 4631

We present a deep optical imaging campaign on the starburst galaxy NGC 4631 with CFHT/MegaCam. By supplementing the HST/ACS and Chandra/ACIS archival data, we search for the optical counterpart candidates of the five brightest X-ray sources in this galaxy, four of which are identified as ultraluminous X-ray sources (ULXs). The stellar environments of the X-ray sources are analyzed using the extinction-corrected color-magnitude diagrams and the isochrone models. We discover a highly asymmetric bubble nebula around X4 which exhibits different morphology in the H$\alpha$ and [O III] images. The [O III]/H$\alpha$ ratio map shows that the H$\alpha$-bright bubble may be formed mainly via the shock ionization by the one-sided jet/outflow, while the more compact [O III] structure is photoionized by the ULX. We constrain the bubble expansion velocity and interstellar medium density with the MAPPINGS V code, and hence estimate the mechanical power injected to the bubble as $P_w \sim 5\times10^{40}$ erg s$^{-1}$ and the corresponding bubble age of $\sim7\times 10^{5}$ yr. Relativistic jets are needed to provide such level of mechanical power with a mass-loss rate of $\sim10^{-7}\ M_{\odot}\ \rm yr^{-1}$. Besides the accretion, the black hole spin is likely an additional energy source for the super-Eddington jet power.Comment: 17 pages, 10 figures, accepted by Ap

Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial

Background The purpose of this study was to assess the efficacy, safety, and pharmacokinetics of cisplatin-based chemotherapy plus cetuximab as first-line treatment in Chinese and Korean patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Methods Patients (n = 68) received cetuximab weekly plus 3-week cycles of cisplatin/5-fluorouracil (5-FU) chemotherapy for up to 6 cycles. The primary endpoint was overall response rate. Results The overall response rate was 55.9%, including 2 complete responses (CRs). Median overall survival (OS) was 12.6 months and median progression-free survival (PFS) was 6.6 months. Grade 3/4 adverse events (AEs) were reported in 41 (60.3%) patients. The safety profile was in line with previous clinical experience. The pharmacokinetic profile was in line with that observed with cetuximab in white and Japanese patients. Conclusion The efficacy, safety, and pharmacokinetic findings from this study support the use of first-line platinum-based chemotherapy plus cetuximab in Chinese and Korean patients with recurrent and/or metastatic SCCHN (ClinicalTrials.gov NCT01177956). © 2014 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 37: 1081–1087, 201

Identification of forensically important sarcophagid flies (Diptera: Sarcophagidae) based on COI gene in China

Abstract: Identifing an insect specimen is a crucial step in forensic entomology. As the stages and species of insect discovered on a corpse, such as Calliphoridae and Sarcophagidae, provides evidence for estimation of postmortem interval (PMI). However, morphologically distinguish may on occasion be impossible to the adult flies and nymphs of the same genus. A molecular method used the cytochrome oxidase subunits one (COI) sequence on mitochondrial DNA was established for sarcophagid species identification. In this study, a 272 base pair region of mitochondrial DNA (mtDNA) coding for COI was investigated for identification of the following forensically important sarcophagid flies. The specimens were from four families, including 8 Boerttcherisca Peregrina (Robineau -Desvoidy,1830) specimens of Boettcherisca, 2 Parasarcophaga similis (Meade, 1876) specimens, 4 Parasarcophaga albiceps (Meigen, 1826) and 8 Parasarcophaga dux (Thompson, 1869) specimens from Parasarcophaga. Phylogenetic analysis indicates that this partial COI region successfully identified all samples species to species group. Low levels of variation between some species indicate that sarcophagid flies from more locations should be studied in the future and local database set up are strongly recommended in China