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Homology modelling

Sarah E Clark, Jeanette E Purcell, Saad Sammani, Earl K Steffen, Marcus J Crim, Robert S Livingston, Cynthia Besch-Williford, Jeffrey D Fortman
A group studying acute lung injury observed an increased percentage of neutrophils in the bronchoalveolar lavage (BAL) fluid of mice. BAL was performed, and lung samples were collected sterilely from 5 C57BL/6 mice that had been bred inhouse. Pure colonies of bacteria, initially identified as Bordetella hinzii were cultured from 2 of the 5 mice which had the highest percentages of neutrophils (21% and 26%) in the BAL fluid. Subsequent sequencing of a portion of the ompA gene from this isolate demonstrated 100% homology with the published B...
2016: Comparative Medicine
Qi Zhang, Zhongduo Wang, Feng Hou, Rachel Harding, Xinyi Huang, Aiping Dong, John R Walker, Yufeng Tong
BACKGROUND: Seven in absentia homologs (SIAHs) comprise a family of highly conserved E3 ubiquitin ligases that play an important role in regulating signalling pathways in tumorigenesis, including the DNA damage repair and hypoxia response pathways. SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high sequence identity of their substrate binding domains (SBDs). Ubiquitin-specific protease USP19 is a deubiquitinase that forms a complex with SIAHs and counteracts the ligase function...
October 21, 2016: Biochimica et Biophysica Acta
Mary A M Cleaton, Claire L Dent, Mark Howard, Jennifer A Corish, Isabelle Gutteridge, Ulla Sovio, Francesca Gaccioli, Nozomi Takahashi, Steven R Bauer, D Steven Charnock-Jones, Theresa L Powell, Gordon C S Smith, Anne C Ferguson-Smith, Marika Charalambous
Pregnancy is a state of high metabolic demand. Fasting diverts metabolism to fatty acid oxidation, and the fasted response occurs much more rapidly in pregnant women than in non-pregnant women. The product of the imprinted DLK1 gene (delta-like homolog 1) is an endocrine signaling molecule that reaches a high concentration in the maternal circulation during late pregnancy. By using mouse models with deleted Dlk1, we show that the fetus is the source of maternal circulating DLK1. In the absence of fetally derived DLK1, the maternal fasting response is impaired...
October 24, 2016: Nature Genetics
Cheng-Gang Ou, Ji-Hua Mao, Li-Jie Liu, Cheng-Jiang Li, Huai-Fu Ren, Zhi-Wei Zhao, Fei-Yun Zhuang
Carrot is generally regarded as a biennial plant with an obligatory vernalization requirement. Early spring cultivation makes carrot plants vulnerable to premature bolting, which results in a loss of commercial value. However, our knowledge of flowering time genes and flowering mechanisms in carrot remain limited. We therefore performed transcriptome analysis to identify the major genes that regulate flowering time in carrot. The bolting behavior of carrot is influenced by low temperature, illumination intensity and photoperiod...
October 24, 2016: Plant Biology
Elisabeth Bezine, Yann Malaisé, Aurore Loeuillet, Marianne Chevalier, Elisa Boutet-Robinet, Bernard Salles, Gladys Mirey, Julien Vignard
The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways...
October 24, 2016: Scientific Reports
Sandeep Kumar, Kavish Kr Jain, Shikha Rani, Kailash N Bhardwaj, Manisha Goel, Ramesh Chander Kuhad
Among lignocellulolytic enzymes, laccases are the most versatile, broadly specific, and largely studied enzyme with a wide range of biotechnological potential. Putative laccase (CotA) from Bacillus pumilus MK001 was cloned and expressed in E. coli. In addition to soluble bioactive fraction, inactive inclusion body fraction was also harvested and refolded under optimized conditions resulting in 64 % of refolding efficiency. The enzyme was found to be thermostable exhibiting a half-life of 60 min at 80 °C...
October 22, 2016: Molecular Biotechnology
Bartosz Roszniowski, Agnieszka Latka, Barbara Maciejewska, Dieter Vandenheuvel, Tomasz Olszak, Yves Briers, Giles S Holt, Miguel A Valvano, Rob Lavigne, Darren L Smith, Zuzanna Drulis-Kawa
Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus...
October 21, 2016: Applied Microbiology and Biotechnology
Zhangguo Chen, Katherine Gowan, Sonia M Leach, Sawanee S Viboolsittiseri, Ameet K Mishra, Tanya Kadoishi, Katrina Diener, Bifeng Gao, Kenneth Jones, Jing H Wang
BACKGROUND: Whole genome next generation sequencing (NGS) is increasingly employed to detect genomic rearrangements in cancer genomes, especially in lymphoid malignancies. We recently established a unique mouse model by specifically deleting a key non-homologous end-joining DNA repair gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in germinal center B cells. This mouse model spontaneously develops mature B cell lymphomas (termed G1XP lymphomas). RESULTS: Here, we attempt to employ whole genome NGS to identify novel structural rearrangements, in particular inter-chromosomal translocations (CTXs), in these G1XP lymphomas...
October 21, 2016: BMC Genomics
Bini Mathew, Judith Varady Hobrath, Larry Ross, Michele C Connelly, Hava Lofton, Malini Rajagopalan, R Kiplin Guy, Robert C Reynolds
A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin...
2016: PloS One
Kristin Bösch, Lamprinos Frantzeskakis, Miroslav Vraneš, Jörg Kämper, Kerstin Schipper, Vera Göhre
Gene deletion plays an important role in the analysis of gene function. One of the most efficient methods to disrupt genes in a targeted manner is the replacement of the entire gene with a selectable marker via homologous recombination. During homologous recombination, exchange of DNA takes place between sequences with high similarity. Therefore, linear genomic sequences flanking a target gene can be used to specifically direct a selectable marker to the desired integration site. Blunt ends of the deletion construct activate the cell's DNA repair systems and thereby promote integration of the construct either via homologous recombination or by non-homologous-end-joining...
September 30, 2016: Journal of Visualized Experiments: JoVE
Shaher Bano Mirza, Ramin Ekhteiari Salmas, M Qaiser Fatmi, Serdar Durdagi
The Klotho is known as lifespan enhancing protein involved in antagonizing the effect of Wnt proteins. Wnt proteins are stem cell regulators, and uninterrupted exposure of Wnt proteins to the cell can cause stem and progenitor cell senescence, which may lead to aging. Keeping in mind the importance of Klotho in Wnt signaling, in silico approaches have been applied to study the important interactions between Klotho and Wnt3 and Wnt3a (wingless-type mouse mammary tumor virus (MMTV) integration site family members 3 and 3a)...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
James West, W Warren Gill
Genome editing in large animals has tremendous practical applications, from more accurate models for medical research through improved animal welfare and production efficiency. Although genetic modification in large animals has a 30 year history, until recently technical issues limited its utility. The original methods - pronuclear injection and integrating viruses - were plagued with problems associated with low efficiency, silencing, poor regulation of gene expression, and variability associated with random integration...
June 2016: Journal of Equine Veterinary Science
Dongkyu Kim, Sook Hee Ku, Hyosuk Kim, Ji Hoon Jeong, Minhyung Lee, Ick Chan Kwon, Donghoon Choi, Sun Hwa Kim
Gene therapy is aimed at selectively knocking up or knocking down the target genes involved in the development of diseases. In many human diseases, dysregulation of disease-associated genes is occurred concurrently: some genes are abnormally turned up and some are turned down. In the field of non-viral gene therapy, plasmid DNA (pDNA) and small interfering RNA (siRNA) are suggested as representative regulation tools for activating and silencing the expression of genes of interest, representatively. Herein, we simultaneously loaded both siRNA (Src homology region 2 domain-containing tyrosine phosphatase-1 siRNA, siSHP-1) for anti-apoptosis and pDNA (hypoxia-inducible vascular endothelial growth factor expression vector, pHI-VEGF) for angiogenesis in a single polymeric nanocarrier and used to synergistically attenuate ischemia-reperfusion (IR)-induced myocardial infarction, which is mainly caused by dysregulating of cardiac apoptosis and angiogenesis...
October 17, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ishita Mukherjee, Abhijit Chakraborty, Saikat Chakrabarti
BACKGROUND: An active immune surveillance and a range of barriers to infection allow the host to effectively eliminate microbial pathogens. However, pathogens may use diverse strategies to subdue such host defences. For instance, one such mechanism is the use of leucine-rich repeat (LRR) proteins by pathogens (microbial) to cause infection. In this study, we aimed at identifying novel virulence factor(s) in Leishmania donovani, based on the possibility of lateral gene transfers of bacterial virulence factor(s) to L...
October 21, 2016: Parasites & Vectors
Félix LaRoche-Johnston, Caroline Monat, Benoit Cousineau
BACKGROUND: Group II introns are catalytically active RNA and mobile retroelements present in certain eukaryotic organelles, bacteria and archaea. These ribozymes self-splice from the pre-mRNA of interrupted genes and reinsert within target DNA sequences by retrohoming and retrotransposition. Evolutionary hypotheses place these retromobile elements at the origin of over half the human genome. Nevertheless, the evolution and dissemination of group II introns was found to be quite difficult to infer...
October 20, 2016: BMC Evolutionary Biology
Kari Branham, Hiroko Matsui, Pooja Biswas, Aditya A Guru, Michael Hicks, John J Suk, He Li, David Jakubosky, Tao Long, Amalio Telenti, Naoki Narai, John R Heckenlively, Kelly A Frazar, Paul A Sieving, Radha Ayyagari
While more than 250 genes are known to cause inherited retinal degenerations (IRD), nearly 40-50% of families have the genetic basis for their disease unknown. In this study we sought to identify the underlying cause of inherited retinal degeneration (IRD) in a family by whole genome sequence (WGS) analysis. Clinical characterization including standard ophthalmic examination, fundus photography, visual field testing, electroretinography, and review of medical and family history was performed. WGS was performed on affected and unaffected family members using Illumina HiSeq X10...
October 7, 2016: Physiological Genomics
Sean Ekins, Alexander L Perryman, Carolina Horta Andrade
The Zika virus outbreak in the Americas has caused global concern. To help accelerate this fight against Zika, we launched the OpenZika project. OpenZika is an IBM World Community Grid Project that uses distributed computing on millions of computers and Android devices to run docking experiments, in order to dock tens of millions of drug-like compounds against crystal structures and homology models of Zika proteins (and other related flavivirus targets). This will enable the identification of new candidates that can then be tested in vitro, to advance the discovery and development of new antiviral drugs against the Zika virus...
October 2016: PLoS Neglected Tropical Diseases
Qiuhong Xue, Caihong Li, Jia Chen, Hongmei Guo, Dongqing Li, Xianglei Wu
CONTEXT: The audiological features and cochlear morphology of individuals with noise-induced hearing loss (NIHL) are well characterized. However, the molecular processes in the cochlea are not well understood. AIMS: To explore the role of the endoplasmic reticulum stress (ERS) response in the guinea pig model of cochlear damage induced by exposure to intense noise. SETTINGS AND DESIGN: A pilot case-control study. SUBJECTS AND METHODS: Forty-eight guinea pigs were divided into four equal groups...
September 2016: Noise & Health
Sushant K Sinha, Shubhasish Goswami, Shibashis Das, Supratim Datta
β-glucosidase (EC; BG) cleaves β-glucosidic linkages in disaccharide or glucose-substituted molecules. In an effort towards designing better BGs, we focused on the role of non-conserved residues across an otherwise homologous BG active site tunnel and designed mutants across the aglycone-binding site (V169C) and the gatekeeper residues (I246A) of the active site tunnel. We expressed in Escherichia coli, the Hore_15280 gene encoding a β-glucosidase (BG) in Halothermothrix orenii. The overexpressed and purified wild-type (B8CYA8) has a high specific activity of 345 μmol/min/mg on pNPGlc and a half-life of 1...
October 20, 2016: Applied Microbiology and Biotechnology
Mi-Sun Kwon, Jaewon Min, Hee-Yeon Jeon, Kwangwoo Hwang, Chuna Kim, Junho Lee, Je-Gun Joung, Woong-Yang Park, Hyunsook Lee
BRCA2 is a multifunctional tumor suppressor involved in homologous recombination (HR), mitotic checkpoint regulation, and telomere homeostasis. Absence of Brca2 in mice results in progressive shortening of telomeres and senescence, yet cells are prone to neoplastic transformation with elongated telomeres, suggesting that BRCA2 has positive and negative effects on telomere length regulation along the path to tumorigenesis. Using Caenorhabditis elegans as a model, we show here that depletion of BRC-2, an ortholog of BRCA2, paradoxically delays senescence in telomerase-deficient mutant worms...
October 2016: FEBS Open Bio
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