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Functional genomics

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https://www.readbyqxmd.com/read/28637339/emergence-of-ceftazidime-avibactam-non-susceptibility-in-an-mdr-klebsiella-pneumoniae-isolate
#1
Anna Both, Henning Büttner, Jiabin Huang, Markus Perbandt, Cristina Belmar Campos, Martin Christner, Florian P Maurer, Stefan Kluge, Christina König, Martin Aepfelbacher, Dominic Wichmann, Holger Rohde
Background: Avibactam is a novel broad-range β-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment. Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I)...
June 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28637297/a-role-for-progesterone-regulated-sfrp4-expression-in-uterine-leiomyomas
#2
Meaghan A Delaney, Ying-Wooi Wan, Gyoung-Eun Kim, Chad J Creighton, Margaret G Taylor, Ramya Masand, Andrew Park, Cecilia Valdes, William Gibbons, Zhandong Liu, Matthew L Anderson
Context: Despite progesterone's key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. Objective: The aim of this study was to identify novel gene products mediating progesterone's effects in uterine leiomyomas. Design: Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28637286/structure-seq2-sensitive-and-accurate-genome-wide-profiling-of-rna-structure-in-vivo
#3
Laura E Ritchey, Zhao Su, Yin Tang, David C Tack, Sarah M Assmann, Philip C Bevilacqua
RNA serves many functions in biology such as splicing, temperature sensing, and innate immunity. These functions are often determined by the structure of RNA. There is thus a pressing need to understand RNA structure and how it changes during diverse biological processes both in vivo and genome-wide. Here, we present Structure-seq2, which provides nucleotide-resolution RNA structural information in vivo and genome-wide. This optimized version of our original Structure-seq method increases sensitivity by at least 4-fold and improves data quality by minimizing formation of a deleterious by-product, reducing ligation bias, and improving read coverage...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637217/experimental-support-that-natural-selection-has-shaped-the-latitudinal-distribution-of-mitochondrial-haplotypes-in-australian-drosophila-melanogaster
#4
M Florencia Camus, Jonci N Wolff, Carla M Sgrò, Damian K Dowling
Cellular metabolism is regulated by enzyme complexes within the mitochondrion, the function of which are sensitive to the prevailing temperature. Such thermal sensitivity, coupled with the observation that population frequencies of mitochondrial haplotypes tend to associate with latitude, altitude or climatic regions across species distributions, led to the hypothesis that thermal selection has played a role in shaping standing variation in the mitochondrial DNA (mtDNA) sequence. This hypothesis, however, remains controversial, and requires evidence that the distribution of haplotypes observed in nature corresponds with the capacity of these haplotypes to confer differences in thermal tolerance...
June 20, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28637205/evolution-and-comparative-genomics-of-paqu-like-conjugative-plasmids-in-vibrio-species
#5
Ruichao Li, Lianwei Ye, Marcus Ho Yin Wong, Zhiwei Zheng, Edward Wai Chi Chan, Sheng Chen
Objectives: To investigate a set of MDR conjugative plasmids found in Vibrio species and characterize the underlying evolution process. Methods: pAQU-type plasmids from Vibrio species were sequenced using both Illumina and PacBio platforms. Bioinformatics tools were utilized to analyse the typical MDR regions and core genes in the plasmids. Results: The nine pAQU-type plasmids ranged from ∼160 to 206 kb in size and were found to harbour as many as 111 core genes encoding conjugative, replication and maintenance functions...
June 20, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28637172/identification-of-four-type-ii-toxin-antitoxin-systems-in-actinobacillus-pleuropneumoniae
#6
Chengkun Zheng, Xigong Zhao, Ting Zeng, Manman Cao, Jiali Xu, Guolin Shi, Jinquan Li, Huanchun Chen, Weicheng Bei
Toxin-antitoxin systems are small genetic elements that are widely prevalent in the genomes of bacteria and archaea. These modules have been identified in various bacteria and proposed to play an important role in bacterial physiology and virulence. However, their presence in the genomes of Actinobacillus species has received no attention. In this study, we describe the identification of four type II TA systems in Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia. Reverse transcription PCR analysis revealed that the genes encoding the toxin and antitoxin are co-transcribed...
June 20, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#7
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#8
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636938/the-ldb1-complex-co-opts-ctcf-for-erythroid-lineage-specific-long-range-enhancer-interactions
#9
Jongjoo Lee, Ivan Krivega, Ryan K Dale, Ann Dean
Lineage-specific transcription factors are critical for long-range enhancer interactions, but direct or indirect contributions of architectural proteins such as CCCTC-binding factor (CTCF) to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that an LDB1-bound enhancer upstream of carbonic anhydrase 2 (Car2) activates its expression by interacting directly with CTCF at the gene promoter. Both LDB1 and CTCF are required for enhancer-Car2 looping, and the domain of LDB1 contacted by CTCF is necessary to rescue Car2 transcription in LDB1-deficient cells...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636886/sirt1-enzymatically-potentiates-1-25-dihydroxyvitamin-d3-signaling-via-vitamin-d-receptor-deacetylation
#10
Marya S Sabir, Chengcheng Hu, Zainab Khan, Michael A Galligan, Christopher M Dussik, Sanchita Mallick, Angelika Dampf Stone, Shane F Batie, Elizabeth T Jacobs, G Kerr Whitfield, Mark R Haussler, Michael C Heck, Peter W Jurutka
The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1...
June 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#11
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636585/microbiome-a-potential-component-in-the-origin-of-mental-disorders
#12
George B Stefano, Radek Ptacek, Jiri Raboch, Richard M Kream
It is not surprising to find microbiome abnormalities present in psychiatric disorders such as depressive disorders, bipolar disorders, etc. Evolutionary pressure may provide an existential advantage to the host eukaryotic cells in that it survives in an extracellular environment containing non-self cells (e.g., bacteria). This phenomenon is both positive and negative, as with other intercellular processes. In this specific case, the phenomenal amount of information gained from combined bacterial genome could enhance communication between self and non-self cells...
June 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28635624/effects-of-type-1-diabetes-risk-alleles-on-immune-cell-gene-expression
#13
REVIEW
Ramesh Ram, Grant Morahan
Genetic studies have identified 61 variants associated with the risk of developing Type 1 Diabetes (T1D). The functions of most of the non-HLA (Human Leukocyte Antigen) genetic variants remain unknown. We found that only 16 of these risk variants could potentially be linked to a protein-coding change. Therefore, we investigated whether these variants affected susceptibility by regulating changes in gene expression. To do so, we examined whole transcriptome profiles of 600 samples from the Type 1 Diabetes Genetics Consortium (T1DGC)...
June 21, 2017: Genes
https://www.readbyqxmd.com/read/28635588/genome-sequence-variation-in-the-constricta-strain-dramatically-alters-the-protein-interaction-and-localization-map-of-potato-yellow-dwarf-virus
#14
Chanyong Jang, Renyuan Wang, Joseph Wells, Fabian Leon, Mark Farman, John Hammond, Michael M Goodin
The genome sequence of the constricta strain of Potato yellow dwarf virus (CYDV) was determined to be 12 792 nt long and organized into seven ORFs with the gene order 3'-N-X-P-Y-M-G-L-5', which encodes the nucleocapsid, phospho, movement, matrix, glyco, and RNA-dependent RNA polymerase proteins, respectively, except for X, which is of unknown function. Cloned ORFs for each gene, except L, were used to construct a protein interaction and localization map (PILM) for this virus, which shares greater than 80 % amino acid similarity in all ORFs except X and P with the sanguinolenta strain of this species (SYDV)...
June 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28635542/gene-expression-study-of-mitochondrial-complex-i-in-schizophrenia-and-paranoid-personality-disorder
#15
Arvin Haghighatfard, Sarah Andalib, Mozhdeh Amini Faskhodi, Soha Sadeghi, Amir Hossein Ghaderi, Shadi Moradkhani, Jalal Rostampour, Zeinab Tabrizi, Ali Mahmoodi, Talie Karimi, Zakieh Ghadimi
OBJECTIVES: The aetiology and molecular mechanisms of schizophrenia (SCZ) and paranoid personality disorder (PPD) are not yet clarified. The present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in the aetiology and characteristics of SCZ and PPD. METHODS: mRNA levels of all genomic and mitochondrial genes which encode mitochondrial complex I subunits (44 genes) were assessed in blood in 634 SCZ, 340 PPD patients and 528 non-psychiatric subjects using quantitative real-time PCR, and associated comprehensive psychiatric, neurological and biochemical assessments...
February 20, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28635424/genome-wide-linkage-and-haplotype-sharing-analysis-implicates-the-mcdr3-locus-as-a-candidate-region-for-a-developmental-macular-disorder-in-association-with-digit-abnormalities
#16
Valentina Cipriani, Ambreen Kalhoro, Gavin Arno, Raquel S Silva, Nikolas Pontikos, Virginie Puech, Michelle E McClements, David M Hunt, Veronica van Heyningen, Michel Michaelides, Andrew R Webster, Anthony T Moore, Bernard Puech
BACKGROUND: Developmental macular disorders are a heterogeneous group of rare retinal conditions that can cause significant visual impairment from childhood. Among these disorders, autosomal dominant North Carolina macular dystrophy (NCMD) has been mapped to 6q16 (MCDR1) with recent support for a non-coding disease mechanism of PRDM13. A second locus on 5p15-5p13 (MCDR3) has been implicated in a similar phenotype, but the disease-causing mechanism still remains unknown. METHODS: Two families affected by a dominant developmental macular disorder that closely resembles NCMD in association with digit abnormalities were included in the study...
March 2, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28635326/encapsulins-molecular-biology-of-the-shell
#17
Robert J Nichols, Caleb Cassidy-Amstutz, Thawatchai Chaijarasphong, David F Savage
Compartmentalization is both a fundamental principle of cellular organization and an emerging theme in prokaryotic biology. Work in the past few decades has shown that protein-based organelles called microcompartments enhance the function of encapsulated cargo proteins. More recently, the repertoire of known prokaryotic organelles has expanded beyond microcompartments to include a new class of smaller proteinaceous compartments, termed nanocompartments (also known as encapsulins). Nanocompartments are icosahedral capsids that are smaller and less complex than microcompartments...
June 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28635135/the-gene-expression-landscape-of-pine-seedling-tissues
#18
Rafael A Cañas, Zhen Li, M Belén Pascual, Vanessa Castro-Rodríguez, Concepción Ávila, Lieven Sterck, Yves Van de Peer, Francisco M Cánovas
Conifers dominate vast regions of the Northern hemisphere. They are the main source of raw materials for timber industry as well as a wide range of biomaterials. Despite their inherent difficulties as experimental models for classical plant biology research, the technological advances in genomics research are enabling fundamental studies on these plants. The use of laser capture microdissection followed by transcriptomic analysis is a powerful tool for unravelling the molecular and functional organization of conifer tissues and specialized cells...
June 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28635106/long-noncoding-rna-and-its-contribution-to-autism-spectrum-disorders
#19
REVIEW
Jie Tang, Yizhen Yu, Wei Yang
Recent studies have indicated that long noncoding RNAs (lncRNAs) play important roles in multiple processes, such as epigenetic regulation, gene expression regulation, development, nutrition-related and other diseases, toxic response, and response to drugs. Although the functional roles and mechanisms of several lncRNAs have been discovered, a better understanding of the vast majority of lncRNAs remains elusive. To understand the functional roles and mechanisms of lncRNAs is critical because these transcripts represent the majority of the transcriptional output of the mammalian genome...
June 20, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28635103/uncovering-the-dispersion-history-adaptive-evolution-and-selection-of-wheat-in-china
#20
Yong Zhou, Zhongxu Chen, Mengping Cheng, Jian Chen, Tingting Zhu, Rui Wang, Yaxi Liu, Pengfei Qi, Guoyue Chen, Qiantao Jiang, Yuming Wei, Ming-Cheng Luo, Eviatar Nevo, Robin G Allaby, Dengcai Liu, Jirui Wang, Jan Dvorák, Youliang Zheng
Wheat was introduced to China approximately 4500 years ago, where it adapted over a span of time to various environments in agro-ecological growing zones. We investigated 717 Chinese and 14 Iranian/Turkish geographically diverse, locally adapted wheat landraces with 27,933 DArTseq (for 717 landraces) and 312,831 Wheat660K (for a subset of 285 landraces) markers. This study highlights the adaptive evolutionary history of wheat cultivation in China. Environmental stresses and independent selection efforts have resulted in considerable genome-wide divergence at the population level in Chinese wheat landraces...
June 21, 2017: Plant Biotechnology Journal
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