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https://www.readbyqxmd.com/read/29457340/key-role-of-tfeb-nucleus-translocation-for-silver-nanoparticle-induced-cytoprotective-autophagy
#1
Jun Lin, Yiming Liu, Hao Wu, Zhihai Huang, Jingfan Ma, Chang Guo, Feng Gao, Peipei Jin, Pengfei Wei, Yunjiao Zhang, Liu Liu, Rui Zhang, Longxin Qiu, Ning Gu, Longping Wen
Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a well-established mechanism involving dephosphorylation of TFEB at serine-142 and serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus translocation precedes autophagy induced by Ag NPs and leads to enhanced expression of autophagy-essential genes...
February 19, 2018: Small
https://www.readbyqxmd.com/read/29453406/crispr-cas9-a-tool-to-efficiently-increase-the-development-of-recombinant-african-swine-fever-viruses
#2
Manuel V Borca, Lauren G Holinka, Keith A Berggren, Douglas P Gladue
African swine fever virus (ASFV) causes a highly contagious disease called African swine fever. This disease is often lethal for domestic pigs, causing extensive losses for the swine industry. ASFV is a large and complex double stranded DNA virus. Currently there is no commercially available treatment or vaccine to prevent this devastating disease. Development of recombinant ASFV for producing live-attenuated vaccines or studying the involvement of specific genes in virus virulence has relied on the relatively rare event of homologous recombination in primary swine macrophages, causing difficulty to purify the recombinant virus from the wild-type parental ASFV...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29443056/primordial-germ-cell-transplantation-for-crispr-cas9-based-leapfrogging-in-xenopus
#3
Ira L Blitz
The creation of mutant lines by genome editing is accelerating genetic analysis in many organisms. CRISPR/Cas9 methods have been adapted for use in the African clawed frog, Xenopus, a longstanding model organism for biomedical research. Traditional breeding schemes for creating homozygous mutant lines with CRISPR/Cas9-targeted mutagenesis have several time-consuming and laborious steps. To facilitate the creation of mutant embryos, particularly to overcome the obstacles associated with knocking out genes that are essential for embryogenesis, a new method called leapfrogging was developed...
February 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29435491/genomewide-identification-of-essential-genes-and-fitness-determinants-of-streptococcus-mutans-ua159
#4
Robert C Shields, Lin Zeng, David J Culp, Robert A Burne
Transposon mutagenesis coupled with next-generation DNA sequencing (Tn-seq) is a powerful tool for discovering regions of the genome that are required for the survival of bacteria in different environments. We adapted this technique to the dental caries pathogen Streptococcus mutans UA159 and identified 11% of the genome as essential, with many genes encoding products required for replication, translation, lipid metabolism, and cell wall biogenesis. Comparison of the essential genome of S. mutans UA159 with those of selected other streptococci for which such information is available revealed several metabolic pathways and genes that are required in S...
January 2018: MSphere
https://www.readbyqxmd.com/read/29431919/host-induced-gene-silencing-of-a-regulator-of-g-protein-signaling-gene-vdrgs1-confers-resistance-to-verticillium-wilt-in-cotton
#5
Jun Xu, Xinyu Wang, Yongqing Li, Jianguo Zeng, Guilin Wang, Chaoyang Deng, Wangzhen Guo
Verticillium wilt (VW), caused by soil-borne fungi of the genus Verticillium, is a serious disease affecting a wide range of plants and leading to a constant and major challenge to agriculture worldwide. Cotton (Gossypium hirsutum) is the world's most important natural textile fiber and oil crop. VW of cotton is a highly devastating vascular disease, however, few resistant germplasms have been reported in cotton. An increasing number of studies have shown that RNA interference (RNAi) based host-induced gene silencing (HIGS) is an effective strategy for improving plant resistance to pathogens by silencing genes essential for the pathogenicity of these pathogens...
February 12, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29404683/an-enhanced-genome-scale-metabolic-reconstruction-of-streptomyces-clavuligerus-identifies-novel-strain-improvement-strategies
#6
León Toro, Laura Pinilla, Claudio Avignone-Rossa, Rigoberto Ríos-Estepa
In this work, we expanded and updated a genome-scale metabolic model of Streptomyces clavuligerus. The model includes 1021 genes and 1494 biochemical reactions; genome-reaction information was curated and new features related to clavam metabolism and to the biomass synthesis equation were incorporated. The model was validated using experimental data from the literature and simulations were performed to predict cellular growth and clavulanic acid biosynthesis. Flux balance analysis (FBA) showed that limiting concentrations of phosphate and an excess of ammonia accumulation are unfavorable for growth and clavulanic acid biosynthesis...
February 5, 2018: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/29402884/target-identification-of-small-molecules-using-large-scale-crispr-cas-mutagenesis-scanning-of-essential-genes
#7
Jasper Edgar Neggers, Bert Kwanten, Tim Dierckx, Hiroki Noguchi, Arnout Voet, Lotte Bral, Kristien Minner, Bob Massant, Nicolas Kint, Michel Delforge, Thomas Vercruysse, Erkan Baloglu, William Senapedis, Maarten Jacquemyn, Dirk Daelemans
Unraveling the mechanism of action and molecular target of small molecules remains a major challenge in drug discovery. While many cancer drugs target genetic vulnerabilities, loss-of-function screens fail to identify essential genes in drug mechanism of action. Here, we report CRISPRres, a CRISPR-Cas-based genetic screening approach to rapidly derive and identify drug resistance mutations in essential genes. It exploits the local genetic variation created by CRISPR-Cas-induced non-homologous end-joining (NHEJ) repair to generate a wide variety of functional in-frame mutations...
February 5, 2018: Nature Communications
https://www.readbyqxmd.com/read/29398941/identify-qtls-for-grain-size-and-weight-in-common-wild-rice-using-chromosome-segment-substitution-lines-across-six-environments
#8
Lan Qi, Yan Sun, Jing Li, Long Su, Xiaoming Zheng, Xiaoning Wang, Kaimian Li, Qingwen Yang, Weihua Qiao
Grain size and weight are important determinants of rice yield. The identification of beneficial genes from wild rice that have been lost or weakened in cultivated rice has become increasingly important for modern breeding strategies. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) of wild rice, Oryza rufipogon with the indica cultivar 9311 genetic background. Four grain-related traits, i.e., grain length (GL), grain width (GW), length-width ratio (LWR), and thousand grain weight (TGW), were screened across six environments...
December 2017: Breeding Science
https://www.readbyqxmd.com/read/29393020/analysis-of-essential-gene-dynamics-under-antibiotic-stress-in-streptococcus-sanguinis
#9
Fadi El-Rami, Xiangzhen Kong, Hardik Parikh, Bin Zhu, Victoria Stone, Todd Kitten, Ping Xu
The paradoxical response of Streptococcus sanguinis to drugs prescribed for dental and clinical practices has complicated treatment guidelines and raised the need for further investigation. We conducted a high throughput study on concomitant transcriptome and proteome dynamics in a time course to assess S. sanguinis behaviour under a sub-inhibitory concentration of ampicillin. Temporal changes at the transcriptome and proteome level were monitored to cover essential genes and proteins over a physiological map of intricate pathways...
February 2018: Microbiology
https://www.readbyqxmd.com/read/29391275/ortholog-based-screening-and-identification-of-genes-related-to-intracellular-survival
#10
Xiaowen Yang, Jiawei Wang, Guoxia Bing, Pengfei Bie, Yanyan De, Yanli Lyu, Qingmin Wu
Bioinformatics and comparative genomics analysis methods were used to predict unknown pathogen genes based on homology with identified or functionally clustered genes. In this study, the genes of common pathogens were analyzed to screen and identify genes associated with intracellular survival through sequence similarity, phylogenetic tree analysis and the λ-Red recombination system test method. The total 38,952 protein-coding genes of common pathogens were divided into 19,775 clusters. As demonstrated through a COG analysis, information storage and processing genes might play an important role intracellular survival...
January 29, 2018: Gene
https://www.readbyqxmd.com/read/29382827/probability-of-phenotypically-detectable-protein-damage-by-enu-induced-mutations-in-the-mutagenetix-database
#11
Tao Wang, Chun Hui Bu, Sara Hildebrand, Gaoxiang Jia, Owen M Siggs, Stephen Lyon, David Pratt, Lindsay Scott, Jamie Russell, Sara Ludwig, Anne R Murray, Eva Marie Y Moresco, Bruce Beutler
Computational inference of mutation effects is necessary for genetic studies in which many mutations must be considered as etiologic candidates. Programs such as PolyPhen-2 predict the relative severity of damage caused by missense mutations, but not the actual probability that a mutation will reduce/eliminate protein function. Based on genotype and phenotype data for 116,330 ENU-induced mutations in the Mutagenetix database, we calculate that putative null mutations, and PolyPhen-2-classified "probably damaging", "possibly damaging", or "probably benign" mutations have, respectively, 61%, 17%, 9...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29374072/asb2%C3%AE-filamin-a-axis-is-essential-for-actin-cytoskeleton-remodeling-during-heart-development
#12
Arnaud Métais, Isabelle Lamsoul, Armelle Melet, Sandrine Uttenweiler-Joseph, Renaud Poincloux, Sonia Stefanovic, Amélie Valière, Anne Gonzalez de Peredo, Alexandre Stella, Odile Burlet-Schiltz, Stephane Zaffran, Pierre G Lutz, Christel Moog-Lutz
Rationale: Heart development involves differentiation of cardiac progenitors and assembly of the contractile sarcomere apparatus of cardiomyocytes. However, little is known about the mechanisms that regulate actin cytoskeleton remodeling during cardiac cell differentiation. Objective: The Asb2α Cullin5 RING E3 ubiquitin ligase triggers polyubiquitylation and subsequent degradation by the proteasome of filamins. Here, we investigate the role of Asb2α in heart development and its mechanisms of action. Methods and Results: : Using ASB2 knockout embryos, we show that Asb2 is an essential gene, critical to heart morphogenesis and function, although its loss does not interfere with the overall patterning of the embryonic heart tube...
January 26, 2018: Circulation Research
https://www.readbyqxmd.com/read/29371219/gemin4-is-an-essential-gene-in-mice-and-its-overexpression-in-human-cells-causes-relocalization-of-the-smn-complex-to-the-nucleoplasm
#13
Ingo D Meier, Michael P Walker, A Gregory Matera
Gemin4 is a member of the Survival Motor Neuron (SMN) protein complex, which is responsible for the assembly and maturation of Sm-class small nuclear ribonucleoproteins (snRNPs). In metazoa, Sm snRNPs are assembled in the cytoplasm and subsequently imported into the nucleus. We previously showed that the SMN complex is required for snRNP import in vitro, although it remains unclear which specific components direct this process. Here, we report that Gemin4 overexpression drives SMN and the other Gemin proteins from the cytoplasm into the nucleus...
January 25, 2018: Biology Open
https://www.readbyqxmd.com/read/29369417/characterization-of-nlhox3-an-essential-gene-for-embryonic-development-in-nilaparvata-lugens
#14
Ze-Wei Ren, Ji-Chong Zhuo, Chuan-Xi Zhang, Dun Wang
Hox genes encode transcriptional regulatory proteins that control axial patterning in all bilaterians. The brown planthopper (BPH), Nilaparvata lugens (Hemiptera: Delphacidae), is a destructive insect pest of rice plants in Asian countries. During analysis of the N. lugens transcriptome, we identified a Hox3-like gene (NlHox3) that was highly and specifically expressed in the embryonic stage. We performed functional analysis on the gene to identify its roles in embryonic development and its potential use as a target in RNA interference (RNAi) based pest control...
January 25, 2018: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29358288/fks2-and-fks3-genes-of-opportunistic-human-pathogen-candida-albicans-influence-echinocandin-susceptibility
#15
Sumanun Suwunnakorn, Hironao Wakabayashi, Milena Kordalewska, David S Perlin, Elena Rustchenko
Candida albicans, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous FKS genes that are evolutionary conserved. One of these, the essential gene FKS1, encodes the catalytic subunit of glucan synthase (GS) that is the target of echinocandin drugs and also serves as site of drug resistance. The two other GS-encoding genes, FKS2 and FKS3, are also expressed but their role in resistance is considered unimportant. However, we report here that expression of FKS1 is upregulated in strains lacking either FKS2 or FKS3 Furthermore, in contrast to what is observed in heterozygous FKS1 deletion strains, cells lacking FKS2 or FKS3 contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs and, consistently, are tolerant to cell wall damaging agents...
January 22, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29351733/glutamate-synthases-from-conifers-gene-structure-and-phylogenetic-studies
#16
Ángel García-Gutiérrez, Francisco M Cánovas, Concepción Ávila
BACKGROUND: Plants synthesize glutamate from ammonium by the combined activity of the enzymes glutamine synthetase (GS) and glutamate synthase (GOGAT) through the glutamate synthase cycle. In plants, there are two forms of glutamate synthases that differ in their electron donors, NADH-GOGAT (EC 1.4.1.14) and Fd-GOGAT (EC 1.4.7.1), which have differential roles either in primary ammonia assimilation or in the reassimilation of ammonium from different catabolic processes. Glutamate synthases are complex iron-sulfur flavoproteins containing functional domains involved in the control and coordination of their catalytic activities in annual plants...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29351550/differential-actions-of-ppar-%C3%AE-and-ppar-%C3%AE-%C3%AE-on-beige-adipocyte-formation-a-study-in-the-subcutaneous-white-adipose-tissue-of-obese-male-mice
#17
Tamiris Lima Rachid, Flavia Maria Silva-Veiga, Francielle Graus-Nunes, Isabele Bringhenti, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29339407/genomic-identification-and-functional-characterization-of-essential-genes-in-caenorhabditis-elegans
#18
Zhaozhao Qin, Robert Johnsen, Shicheng Yu, Jeffrey Shih-Chieh Chu, David Baillie, Nansheng Chen
Using combined genetic mapping, Illumina sequencing, bioinformatics analyses, and experimental validation, we identified 60 essential genes from 104 lethal mutations in two genomic regions of C. elegans totalling approximately 14 Mb on chromosome III(mid) and chromosome V(left). Five of the 60 genes had not previously been shown to have lethal phenotypes by RNA interference depletion. By analyzing the regions around the lethal missense mutations, we identified four putative new protein functional domains. Furthermore, functional characterization of the identified essential genes shows that most are enzymes, including helicases, tRNA synthetases, and kinases in addition to ribosomal proteins...
January 16, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29330052/esco2-knockdown-inhibits-cell-proliferation-and-induces-apoptosis-in-human-gastric-cancer-cells
#19
Hongmei Chen, Lei Zhang, Wenting He, Liu Tao, Yang Zhao, Hao Chen, Yumin Li
Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29325119/mir-96-is-required-for-normal-development-of-the-auditory-hindbrain
#20
Tina Schlüter, Christina Berger, Elena Rosengauer, Pascal Fieth, Constanze Krohs, Kathy Ushakov, Karen P Steel, Karen B Avraham, Alexander Hartmann, Felix Felmy, Hans Gerd Nothwang
The peripheral deafness gene Mir96 is expressed in both the cochlea and central auditory circuits. To investigate whether it plays a role in the auditory system beyond the cochlea, we characterized homozygous Dmdo/Dmdo mice with a point mutation in miR-96. Anatomical analysis demonstrated a significant decrease in volume of auditory nuclei in Dmdo/Dmdo mice. This decrease resulted from decreased cell size. Non-auditory structures in the brainstem of Dmdo/Dmdo mice or auditory nuclei of the congenital deaf Cldn14-/- mice revealed no such differences...
January 9, 2018: Human Molecular Genetics
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