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https://www.readbyqxmd.com/read/28538179/hand2-target-gene-regulatory-networks-control-atrioventricular-canal-and-cardiac-valve-development
#1
Frédéric Laurent, Ausra Girdziusaite, Julie Gamart, Iros Barozzi, Marco Osterwalder, Jennifer A Akiyama, Joy Lincoln, Javier Lopez-Rios, Axel Visel, Aimée Zuniga, Rolf Zeller
The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28535294/hgva-the-human-genome-variation-archive
#2
Javier Lopez, Jacobo Coll, Matthias Haimel, Swaathi Kandasamy, Joaquin Tarraga, Pedro Furio-Tari, Wasim Bari, Marta Bleda, Antonio Rueda, Stefan Gräf, Augusto Rendon, Joaquin Dopazo, Ignacio Medina
High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion...
May 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28535261/recruitment-of-a-lineage-specific-virulence-regulatory-pathway-promotes-intracellular-infection-by-a-plant-pathogen-experimentally-evolved-into-a-legume-symbiont
#3
Delphine Capela, Marta Marchetti, Camille Clérissi, Anthony Perrier, Dorian Guetta, Carine Gris, Marc Valls, Alain Jauneau, Stéphane Cruveiller, Eduardo P C Rocha, Catherine Masson-Boivin
Ecological transitions between different lifestyles, such as pathogenicity, mutualism and saprophytism, have been very frequent in the course of microbial evolution, and often driven by horizontal gene transfer. Yet, how genomes achieve the ecological transition initiated by the transfer of complex biological traits remains poorly known. Here we used experimental evolution, genomics, transcriptomics and high-resolution phenotyping to analyze the evolution of the plant pathogen Ralstonia solanacearum into legume symbionts, following the transfer of a natural plasmid encoding the essential mutualistic genes...
May 23, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28535251/mms1-binds-to-g-rich-regions-in-saccharomyces-cerevisiae-and-influences-replication-and-genome-stability
#4
Katharina Wanzek, Eike Schwindt, John A Capra, Katrin Paeschke
The regulation of replication is essential to preserve genome integrity. Mms1 is part of the E3 ubiquitin ligase complex that is linked to replication fork progression. By identifying Mms1 binding sites genome-wide in Saccharomyces cerevisiae we connected Mms1 function to genome integrity and replication fork progression at particular G-rich motifs. This motif can form G-quadruplex (G4) structures in vitro. G4 are stable DNA structures that are known to impede replication fork progression. In the absence of Mms1, genome stability is at risk at these G-rich/G4 regions as demonstrated by gross chromosomal rearrangement assays...
May 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28534478/complementary-information-derived-from-crispr-cas9-mediated-gene-deletion-and-suppression
#5
Joseph Rosenbluh, Han Xu, William Harrington, Stanley Gill, Xiaoxing Wang, Francisca Vazquez, David E Root, Aviad Tsherniak, William C Hahn
CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534452/the-recurrent-domestication-of-viruses-major-evolutionary-transitions-in-parasitic-wasps
#6
Jérémy Gauthier, Jean-Michel Drezen, Elisabeth A Herniou
Several lineages of endoparasitoid wasps, which develop inside the body of other insects, have domesticated viruses, used as delivery tools of essential virulence factors for the successful development of their progeny. Virus domestications are major evolutionary transitions in highly diverse parasitoid wasps. Much progress has recently been made to characterize the nature of these ancestrally captured endogenous viruses that have evolved within the wasp genomes. Virus domestication from different viral families occurred at least three times in parasitoid wasps...
May 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28534088/the-ppar-gamma-binding-sequence-pal3-is-necessary-for-basal-but-dispensable-for-high-fat-diet-regulated-human-renin-expression-in-the-kidney
#7
Peter Lachmann, Jenny Selbmann, Linda Hickmann, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of accompanying arterial hypertension. We used bacterial artificial chromosome construct and co-placement strategy to generate two transgenic mouse lines expressing the human renin gene from identical genomic locus without affecting the intrinsic mouse renin expression...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28533502/clinical-value-and-prospective-pathway-signaling-of-microrna-375-in-lung-adenocarcinoma-a-study-based-on-the-cancer-genome-atlas-tcga-gene-expression-omnibus-geo-and-bioinformatics-analysis
#8
Ting-Qing Gan, Wen-Jie Chen, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Lin-Jiang Pan, Zu-Yun Li, Gang Chen
BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated. MATERIAL AND METHODS We evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis...
May 23, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28533456/colour-vision-and-coevolution-in-avian-brood-parasitism
#9
REVIEW
Mary Caswell Stoddard, Mark E Hauber
The coevolutionary interactions between avian brood parasites and their hosts provide a powerful system for investigating the diversity of animal coloration. Specifically, reciprocal selection pressure applied by hosts and brood parasites can give rise to novel forms and functions of animal coloration, which largely differ from those that arise when selection is imposed by predators or mates. In the study of animal colours, avian brood parasite-host dynamics therefore invite special consideration. Rapid advances across disciplines have paved the way for an integrative study of colour and vision in brood parasite-host systems...
July 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28533395/integrative-modeling-of-gene-and-genome-evolution-roots-the-archaeal-tree-of-life
#10
Tom A Williams, Gergely J Szöllősi, Anja Spang, Peter G Foster, Sarah E Heaps, Bastien Boussau, Thijs J G Ettema, T Martin Embley
A root for the archaeal tree is essential for reconstructing the metabolism and ecology of early cells and for testing hypotheses that propose that the eukaryotic nuclear lineage originated from within the Archaea; however, published studies based on outgroup rooting disagree regarding the position of the archaeal root. Here we constructed a consensus unrooted archaeal topology using protein concatenation and a multigene supertree method based on 3,242 single gene trees, and then rooted this tree using a recently developed model of genome evolution...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533217/transcriptional-control-of-the-lateral-flagellar-genes-of-bradyrhizobium-diazoefficiens
#11
Elías J Mongiardini, J Ignacio Quelas, Carolina Dardis, M Julia Althabegoiti, Aníbal R Lodeiro
Bradyrhizobium diazoefficiens, the soybean N2-fixing symbiont, possesses a dual flagellar system comprising a constitutive subpolar flagellum and inducible lateral flagella. Here, we analyzed the genomic organization and biosynthetic regulation of the lateral-flagellar genes. We found that those genes are located in a single genomic cluster, organized in two monocistronic transcriptional units and three operons, one possibly containing an internal transcription start site. Among the monocistronic units is blr6846, homologous to the Class-IB master regulators of flagella synthesis in Brucella melitensis and Ensifer meliloti, and required for the expression of all the lateral-flagellar genes except lafA2, which locus encodes a single lateral flagellin...
May 22, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28532976/microbiological-problems-and-biofilms-associated-with-mycobacterium-chimaera-in-heater-cooler-units-used-for-cardiopulmonary-bypass
#12
REVIEW
J Walker, G Moore, S Collins, S Parks, M I Garvey, T Lamagni, G Smith, L Dawkin, S Goldenberg, M Chand
The role of heater-cooler units (HCUs) in the transmission of Mycobacterium chimaera during open heart surgery has been recognized since 2013. Subsequent investigations uncovered a remarkable global outbreak reflecting the wide distribution of implicated devices. HCUs are an essential component of cardiopulmonary bypass operations and their withdrawal would severely affect capacity for life-saving cardiac surgery. However, studies have demonstrated that many HCUs are contaminated with a wide range of micro-organisms, including M...
April 26, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28532794/immunogenicity-of-phospholipase-a2-toxins-and-their-role-in-streptococcus-equi-pathogenicity
#13
M R López-Álvarez, M Salze, A Cenier, C Robinson, R Paillot, A S Waller
Streptococcus equi subsp. equi (S. equi) is the causative agent of strangles, one of the most frequently diagnosed infectious diseases of horses worldwide. Phospholipase A2 toxins (PLA2) cleave phospholipid molecules at position sn-2 contributing to the production of leukotrienes that are important inflammatory mediators. Two homologous phospholipases, SlaA and SlaB are encoded by the S. equi genome suggesting that PLA2 toxins may contribute to its pathogenicity. Here we report the immunogenicity and role of PLA2 toxins during natural and experimental infection of horses with S...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28532625/v-d-j-recombination-exploits-dna-damage-responses-to-promote-immunity
#14
REVIEW
Rahul Arya, Craig H Bassing
It has been recognized for 40 years that the variable (diversity) joining [V(D)J] recombination-mediated assembly of diverse B and T lymphocyte antigen receptor (AgR) genes is not only essential for adaptive immunity, but also a risk for autoimmunity and lymphoid malignancies. Over the past few years, several studies have revealed that recombination-activating gene (RAG) endonuclease-induced DNA double-strand breaks (DSBs) transcend hazardous intermediates during antigen receptor gene assembly. RAG cleavage within the genomes of lymphocyte progenitors and immature lymphocytes regulates the expression of ubiquitous and lymphocyte-specific gene transcripts to control the differentiation and function of both adaptive and innate immune cell lineages...
May 19, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28531898/plasma-et-1-concentrations-are-elevated-in-patients-with-hypertension-meta-analysis-of-clinical-studies
#15
Mei Xu, Yong-Ping Lu, Ahmed Abdallah Hasan, Berthold Hocher
BACKGROUND/AIMS: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. METHODS: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks...
May 26, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28531220/highly-conserved-type-1-pili-promote-enterotoxigenic-e-coli-pathogen-host-interactions
#16
Alaullah Sheikh, Rasheduzzaman Rashu, Yasmin Ara Begum, F Matthew Kuhlman, Matthew A Ciorba, Scott J Hultgren, Firdausi Qadri, James M Fleckenstein
Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host...
May 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28531161/development-of-optimized-inhibitor-rnas-allowing-multisite-targeting-of-the-hcv-genome
#17
Cristina Romero-López, Thomas Lahlali, Beatriz Berzal-Herranz, Alfredo Berzal-Herranz
Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs...
May 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28530713/bach2-immunodeficiency-illustrates-an-association-between-super-enhancers-and-haploinsufficiency
#18
Behdad Afzali, Juha Grönholm, Jana Vandrovcova, Charlotte O'Brien, Hong-Wei Sun, Ine Vanderleyden, Fred P Davis, Ahmad Khoder, Yu Zhang, Ahmed N Hegazy, Alejandro V Villarino, Ira W Palmer, Joshua Kaufman, Norman R Watts, Majid Kazemian, Olena Kamenyeva, Julia Keith, Anwar Sayed, Dalia Kasperaviciute, Michael Mueller, Jason D Hughes, Ivan J Fuss, Mohammed F Sadiyah, Kim Montgomery-Recht, Joshua McElwee, Nicholas P Restifo, Warren Strober, Michelle A Linterman, Paul T Wingfield, Holm H Uhlig, Rahul Roychoudhuri, Timothy J Aitman, Peter Kelleher, Michael J Lenardo, John J O'Shea, Nichola Cooper, Arian D J Laurence
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530222/ultrasensitive-and-high-efficiency-screen-of-de-novo-low-frequency-mutations-by-o2n-seq
#19
Kaile Wang, Shujuan Lai, Xiaoxu Yang, Tianqi Zhu, Xuemei Lu, Chung-I Wu, Jue Ruan
Detection of de novo, low-frequency mutations is essential for characterizing cancer genomes and heterogeneous cell populations. However, the screening capacity of current ultrasensitive NGS methods is inadequate owing to either low-efficiency read utilization or severe amplification bias. Here, we present o2n-seq, an ultrasensitive and high-efficiency NGS library preparation method for discovering de novo, low-frequency mutations. O2n-seq reduces the error rate of NGS to 10(-5)-10(-8). The efficiency of its data usage is about 10-30 times higher than that of barcode-based strategies...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529507/a-novel-and-efficient-method-for-bacteria-genome-editing-employing-both-crispr-cas9-and-an-antibiotic-resistance-cassette
#20
Hong Zhang, Qiu-Xiang Cheng, Ai-Min Liu, Guo-Ping Zhao, Jin Wang
As Cas9-mediated cleavage requires both protospacer and protospacer adjacent motif (PAM) sequences, it is impossible to employ the CRISPR/Cas9 system to directly edit genomic sites without available PAM sequences nearby. Here, we optimized the CRISPR/Cas9 system and developed an innovative two-step strategy for efficient genome editing of any sites, which did not rely on the availability of PAM sequences. An antibiotic resistance cassette was employed as both a positive and a negative selection marker. By integrating the optimized two-plasmid CRISPR/Cas system and donor DNA, we achieved gene insertion and point mutation with high efficiency in Escherichia coli, and importantly, obtained clean mutants with no other unwanted mutations...
2017: Frontiers in Microbiology
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