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https://www.readbyqxmd.com/read/29674565/systematic-analysis-of-complex-genetic-interactions
#1
Elena Kuzmin, Benjamin VanderSluis, Wen Wang, Guihong Tan, Raamesh Deshpande, Yiqun Chen, Matej Usaj, Attila Balint, Mojca Mattiazzi Usaj, Jolanda van Leeuwen, Elizabeth N Koch, Carles Pons, Andrius J Dagilis, Michael Pryszlak, Jason Zi Yang Wang, Julia Hanchard, Margot Riggi, Kaicong Xu, Hamed Heydari, Bryan-Joseph San Luis, Ermira Shuteriqi, Hongwei Zhu, Nydia Van Dyk, Sara Sharifpoor, Michael Costanzo, Robbie Loewith, Amy Caudy, Daniel Bolnick, Grant W Brown, Brenda J Andrews, Charles Boone, Chad L Myers
To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions...
April 20, 2018: Science
https://www.readbyqxmd.com/read/29670535/increased-rnai-efficacy-in-spodoptera-exigua-via-the-formulation-of-dsrna-with-guanylated-polymers
#2
Olivier Christiaens, Myriam G Tardajos, Zarel L Martinez Reyna, Mamoni Dash, Peter Dubruel, Guy Smagghe
Lepidoptera comprise some of the most devastating herbivorous pest insects worldwide. One of the most promising novel pest control strategies is exploiting the RNA interference (RNAi) mechanism to target essential genes for knockdown and incite toxic effects in the target species without harming other organisms in the ecosystem. However, many insects are refractory to oral RNAi, often due to rapid degradation of ingested dsRNA in their digestive system. This is the case for many lepidopteran insects, including the beet armyworm Spodoptera exigua , which is characterized by a very alkaline gut environment (pH > 9...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29668953/evolution-of-genome-architecture-in-archaea-spontaneous-generation-of-a-new-chromosome-in-haloferax-volcanii
#3
Darya Ausiannikava, Laura Mitchell, Hannah Marriott, Victoria Smith, Michelle Hawkins, Kira S Makarova, Eugene V Koonin, Conrad A Nieduszynski, Thorsten Allers
The common ancestry of archaea and eukaryotes is evident in their genome architecture. All eukaryotic and several archaeal genomes consist of multiple chromosomes, each replicated from multiple origins. Three scenarios have been proposed for the evolution of this genome architecture: (1) mutational diversification of a multi-copy chromosome; (2) capture of a new chromosome by horizontal transfer; (3) acquisition of new origins and splitting into two replication-competent chromosomes. We report an example of the third scenario: the multi-origin chromosome of the archaeon Haloferax volcanii has split into two elements via homologous recombination...
April 16, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29662178/defining-essential-genes-for-human-pluripotent-stem-cells-by-crispr-cas9-screening-in-haploid-cells
#4
Atilgan Yilmaz, Mordecai Peretz, Aviram Aharony, Ido Sagi, Nissim Benvenisty
The maintenance of pluripotency requires coordinated expression of a set of essential genes. Using our recently established haploid human pluripotent stem cells (hPSCs), we generated a genome-wide loss-of-function library targeting 18,166 protein-coding genes to define the essential genes in hPSCs. With this we could allude to an intrinsic bias of essentiality across cellular compartments, uncover two opposing roles for tumour suppressor genes and link autosomal-recessive disorders with growth-retardation phenotypes to early embryogenesis...
April 16, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29655887/engineering-riboswitch-in-l-major-from-prediction-to-conceptualization
#5
Pruthvi Raj Bejugam, Shailza Singh
Post-transcriptional gene regulation is a vital process to regulate expression of the key genes in the eukaryotic cell. Such processes are essential for pathogens which reside inside the host cell. One such pathogen is Leishmania major, which causes cutaneous leishmaniasis. The parasite lives inside the macrophages of mammalian host (mostly human). Inside the macrophage, Leishmania genes show complex host-pathogen interaction regulating a plethora of gene expression. Till date, most of the studies have shown this kind of regulation with respect to the host macrophages...
April 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29649003/somatic-mutation-of-the-cohesin-complex-subunit-confers-therapeutic-vulnerabilities-in-cancer
#6
Yunhua Liu, Hanchen Xu, Kevin Van der Jeught, Yujing Li, Sheng Liu, Lu Zhang, Yuanzhang Fang, Xinna Zhang, Milan Rodovich, Bryan P Schneider, Xiaoming He, Cheng Huang, Chi Zhang, Jun Wan, Guang Ji, Xiongbin Lu
Synthetic lethality-based strategy has been developed to identify therapeutic targets in cancer harboring tumor suppressor gene mutations, as exemplified by the effectiveness of PARP inhibitors in BRCA1/2-mutated tumors. However, many synthetic lethal interactors are less reliable due to the fact that such genes usually do not perform fundamental or indispensable functions in the cell. Here we developed an approach to identify the "essential lethality" arose from these mutated/deleted essential genes, which are largely tolerated in cancer cells due to genetic redundancy...
April 12, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29624906/stress-effects-of-cyanotoxin-%C3%AE-methylamino-l-alanine-bmaa-on-cyanobacterial-heterocyst-formation-and-functionality
#7
Alexandra A Popova, Ulla Rasmussen, Tatiana A Semashko, Vadim M Govorun, Olga A Koksharova
Various species of cyanobacteria, diatoms and dinoflagellates are capable of synthesizing the non-proteinogenic neurotoxic amino acid β-N-methylamino-L-alanine (BMAA), which is known to be a causative agent of human neurodegeneration. Similar to most cyanotoxins, the biological and ecological functions of BMAA in cyanobacteria are unknown. In this study, we show for the first time that BMAA, in micromolar amounts, inhibits the formation of heterocysts (specialized nitrogen-fixing cells) in heterocystous, diazotrophic cyanobacteria (Anabaena sp...
April 6, 2018: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/29623398/complete-genome-sequence-of-alcaligenes-faecalis-strain-jq135-a-bacterium-capable-of-efficiently-degrading-nicotinic-acid
#8
Yanting Zhang, Qing Chen, Junbin Ji, Lingling Zhao, Lei Zhang, Jiguo Qiu, Jian He
Nicotinic acid (NA), known as vitamin B3, is ubiquitous in nature and plays an important role in living organisms. The microbial catabolism of NA is highly diverse. However, the NA degradation by Alcaligenes faecalis strains has been poorly investigated. In this study, we report the complete genome sequence of A. faecalis JQ135 (4.08 Mbp) and several essential genes for NA degradation. This genome sequence will facilitate to elucidate the molecular metabolism of NA and advance the potential biotechnological applications of A...
April 5, 2018: Current Microbiology
https://www.readbyqxmd.com/read/29620181/identification-of-streptococcus-mitis321a-vaccine-antigens-based-on-reverse-vaccinology
#9
Qiao Zhang, Kexiong Lin, Changzheng Wang, Zhi Xu, Li Yang, Qianli Ma
Streptococcus mitis (S. mitis) may transform into highly pathogenic bacteria. The aim of the present study was to identify potential antigen targets for designing an effective vaccine against the pathogenic S. mitis321A. The genome of S. mitis321A was sequenced using an Illumina Hiseq2000 instrument. Subsequently, Glimmer 3.02 and Tandem Repeat Finder (TRF) 4.04 were used to predict genes and tandem repeats, respectively, with DNA sequence function analysis using the Basic Local Alignment Search Tool (BLAST) in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups of proteins (COG) databases...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29618636/single-cell-profiling-screen-identifies-microtubule-dependent-reduction-of-variability-in-signaling
#10
C Gustavo Pesce, Stefan Zdraljevic, William J Peria, Alan Bush, María Victoria Repetto, Daniel Rockwell, Richard C Yu, Alejandro Colman-Lerner, Roger Brent
Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell-to-cell variability in signal strength and cellular response. Here, we screened 1,141 non-essential genes to identify 50 "variability genes". Most had distinct, separable effects on strength and variability of the PRS, defining these quantities as genetically distinct "axes" of system behavior...
April 4, 2018: Molecular Systems Biology
https://www.readbyqxmd.com/read/29605728/the-l83l-orf-of-african-swine-fever-virus-strain-georgia-encodes-for-a-non-essential-gene-that-interacts-with-the-host-protein-il-1%C3%AE
#11
Manuel V Borca, Vivian O'Donnell, Lauren G Holinka, Elizabeth Ramírez-Medina, Benjamin A Clark, Elizabeth A Vuono, Keith Berggren, Marialexia Alfano, Lucas B Carey, Juergen A Richt, Guillermo R Risatti, Douglas P Gladue
African swine fever virus (ASFV) causes a contagious and frequently lethal disease of pigs causing significant economic consequences to the swine industry. The ASFV genome encodes for more than 150 genes, but only a few of them have been studied in detail. Here we report the characterization of open reading frame L83L which encodes a highly conserved protein across all ASFV isolates. A recombinant ASFV harboring a HA tagged L83L protein was developed (ASFV-G-L83L-HA) and used to demonstrate that L83L is a transiently expressed early virus protein...
March 29, 2018: Virus Research
https://www.readbyqxmd.com/read/29602878/molecular-basis-for-the-structural-diversity-in-serogroup-o2-antigen-polysaccharides-in-klebsiella-pneumoniae
#12
Bradley R Clarke, Olga G Ovchinnikova, Steven D Kelly, Monica L Williamson, Jennifer E Butler, Bin Liu, Lu Wang, Xi Gou, Rainer Follador, Todd L Lowary, Chris Whitfield
Klebsiella pneumoniae is a major health threat. Vaccination and passive immunization are considered as alternative therapeutic strategies for managing Klebsiella infections. Lipopolysaccharide O antigens are attractive candidates because of the relatively small range of known O-antigen polysaccharide structures, but immunotherapeutic applications require a complete understanding of the structures found in clinical settings. Currently, the precise number of Klebsiella O antigens is unknown because available serological tests have limited resolution, and their association with defined chemical structures is sometimes uncertain...
March 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29602068/ectromelia-virus-lacking-the-e3l-ortholog-is-replication-defective-and-nonpathogenic-but-does-induce-protective-immunity-in-a-mouse-strain-susceptible-to-lethal-mousepox
#13
Tiffany R Frey, Katherine S Forsyth, Maura M Sheehan, Brian C De Haven, Julia G Pevarnik, Erin S Hand, Marie C Pizzorno, Laurence C Eisenlohr, Adam R Hersperger
All known orthopoxviruses, including ectromelia virus (ECTV), contain a gene in the E3L family. The protein product of this gene, E3, is a double-stranded RNA-binding protein. It can impact host range and is used by orthopoxviruses to combat cellular defense pathways, such as PKR and RNase L. In this work, we constructed an ECTV mutant with a targeted disruption of the E3L open reading frame (ECTVΔE3L). Infection with this virus resulted in an abortive replication cycle in all cell lines tested. We detected limited transcription of late genes but no significant translation of these mRNAs...
March 27, 2018: Virology
https://www.readbyqxmd.com/read/29599176/h3k4-methylation-dependent-and-independent-chromatin-regulation-by-jhd2-and-set1-in-budding-yeast
#14
Kwan Yin Lee, Ziyan Chen, River Jiang, Marc D Meneghini
Set1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me) through their opposing methyltransferase and demethylase activities in the budding yeast Saccharomyces cerevisiae H3K4me associates with actively transcribed genes and, like both SET1 and JHD2 themselves, is known to regulate gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act solely through H3K4me. Relevantly, Set1 methylates lysine residues in the kinetochore protein Dam1 while genetic studies of the S. pombe SET1 ortholog suggest the existence of non-H3K4 Set1 targets relevant to gene regulation...
March 29, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29598825/combined-flow-cytometry-and-high-throughput-image-analysis-for-the-study-of-essential-genes-in-caenorhabditis-elegans
#15
Blanca Hernando-Rodríguez, Annmary Paul Erinjeri, María Jesús Rodríguez-Palero, Val Millar, Sara González-Hernández, María Olmedo, Bettina Schulze, Ralf Baumeister, Manuel J Muñoz, Peter Askjaer, Marta Artal-Sanz
BACKGROUND: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking...
March 29, 2018: BMC Biology
https://www.readbyqxmd.com/read/29596631/making-point-mutations-in-escherichia-coli-bl21-genome-using-the-crispr-cas9-system
#16
Xiaozhen Wang, Jinghua He, Keyi Le
The CRISPR-Cas9 system is an efficient and rapid tool for genome editing. However, its utilization in bacteria suffers challenges such as the risk of repeated recognition and cutting by Cas9. Here we established a two-step genome editing strategy using Streptococcus pyogenes CRISPR-Cas9 system to achieve a clean mutation with only the target sites into Escherichia coli genome. This strategy can avoid the risk of repeated cutting by gRNA/Cas9 without altering the PAM or inserting additional silent mutations into the genome...
March 27, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29590189/versatile-approach-for-functional-analysis-of-human-proteins-and-efficient-stable-cell-line-generation-using-flp-mediated-recombination-system
#17
Roman J Szczesny, Katarzyna Kowalska, Kamila Klosowska-Kosicka, Aleksander Chlebowski, Ewelina P Owczarek, Zbigniew Warkocki, Tomasz M Kulinski, Dorota Adamska, Kamila Affek, Agata Jedroszkowiak, Anna V Kotrys, Rafal Tomecki, Pawel S Krawczyk, Lukasz S Borowski, Andrzej Dziembowski
Deciphering a function of a given protein requires investigating various biological aspects. Usually, the protein of interest is expressed with a fusion tag that aids or allows subsequent analyses. Additionally, downregulation or inactivation of the studied gene enables functional studies. Development of the CRISPR/Cas9 methodology opened many possibilities but in many cases it is restricted to non-essential genes. Recombinase-dependent gene integration methods, like the Flp-In system, are very good alternatives...
2018: PloS One
https://www.readbyqxmd.com/read/29582753/the-kinetoplastid-infecting-bodo-saltans-virus-bsv-a-window-into-the-most-abundant-giant-viruses-in-the-sea
#18
Christoph M Deeg, Cheryl-Emiliane T Chow, Curtis A Suttle
Giant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant group of giant viruses in ocean metagenomes, and the first isolate of a klosneuvirus, a subgroup of the Mimiviridae proposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastid Bodo saltans . Its 1.39 Mb genome encodes 1227 predicted ORFs, including a complex replication machinery...
March 27, 2018: ELife
https://www.readbyqxmd.com/read/29577977/transcriptome-profiling-and-cataloging-differential-gene-expression-in-floral-buds-of-fertile-and-sterile-lines-of-cotton-gossypium-hirsutum-l
#19
Rasmieh Hamid, Rukam S Tomar, Hassan Marashi, Saeid Malekzadeh Shafaroudi, Balaji A Golakiya, Motahhareh Mohsenpour
Cytoplasmic Male Sterility is maternally inherited trait in plants, characterized by failure to produce functional pollen during anther development. Anther development is modulated through the interaction of nuclear and mitochondrial genes. In the present study, differential gene expression of floral buds at the sporogenous stage (SS) and microsporocyte stage (MS) between CGMS and its fertile maintainer line of cotton plants was studied. A total of 320 significantly differentially expressed genes, including 20 down-regulated and 37 up-regulated in CGMS comparing with its maintainer line at the SS stage, as well as and 89 down-regulated and 4 up-regulated in CGMS compared to the fertile line at MS stage...
March 22, 2018: Gene
https://www.readbyqxmd.com/read/29572390/methionine-adenosyltransferase-4-mediates-dna-and-histone-methylation
#20
Jingjing Meng, Lishuan Wang, Jingyi Wang, Xiaowen Zhao, Jinkui Cheng, Wenxiang Yu, Dan Jin, Qing Li, Zhizhong Gong
DNA and histone methylation co-regulate heterochromatin formation and gene silencing in animals and plants. To identify factors involved in maintaining gene silencing, we conducted a forward genetic screen for mutants that release the silenced transgene Pro35S::NEOMYCIN PHOSPHOTRANSFERASE II in the transgenic Arabidopsis thaliana line L119. We identified MAT4/SAMS3/MTO3/AT3G17390, which encodes methionine adenosyltransferase 4 (MAT4)/S-adenosyl-methionine synthetase 3 that catalyzes the synthesis of S-adenosyl-methionine (SAM) in the one-carbon metabolism cycle...
March 23, 2018: Plant Physiology
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