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Forced gene mutation

Katarzyna Szot-Karpińska, Piotr Golec, Adam Lesniewski, Barbara Palys, Frank Marken, Joanna Niedziółka-Jönsson, Grzegorz Wegrzyn, Marcin Łoś
With the advent of nanotechnology, carbon nanomaterials such as carbon nanofibers (CNF) have aroused substantial interest in various research fields including energy storage and sensing. Further improvement of their properties might be achieved via application of viral particles such as bacteriophages. In this report we present a filamentous M13 bacteriophage, with a point mutation in gene VII (pVII-mutant-M13), that selectively binds to the carbon nanofibers to form 3D structures. The phage-display technique was utilized for the selection of the pVII-mutant-M13 phage from the phage display peptide library...
October 17, 2016: Bioconjugate Chemistry
Emily L Newman, Georgia Gunner, Polly Huynh, Darrel Gachette, Stephen J Moss, Trevor G Smart, Uwe Rudolph, Joseph F DeBold, Klaus A Miczek
BACKGROUND: Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear whether α2-containing GABAA receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. METHODS: Male wild-type (Wt) C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol (EtOH) (S270H/L277A) at α2-containing GABAA receptors were assessed for their binge-like, moderate, or escalated chronic drinking using drinking in the dark, continuous access (CA) and intermittent access (IA) to alcohol protocols, respectively...
September 26, 2016: Alcoholism, Clinical and Experimental Research
Josep Sardanyés, Regina Martínez, Carles Simó, Ricard Solé
The dynamics of heterogeneous tumor cell populations competing with healthy cells is an important topic in cancer research with deep implications in biomedicine. Multitude of theoretical and computational models have addressed this issue, especially focusing on the nature of the transitions governing tumor clearance as some relevant model parameters are tuned. In this contribution, we analyze a mathematical model of unstable tumor progression using the quasispecies framework. Our aim is to define a minimal model incorporating the dynamics of competition between healthy cells and a heterogeneous population of cancer cell phenotypes involving changes in replication-related genes (i...
October 6, 2016: Journal of Mathematical Biology
Toshinori Ozaki, Mizuyo Nakamura, Takehiro Ogata, Meijie Sang, Hiroyuki Yoda, Kiriko Hiraoka, Meixiang Sang, Osamu Shimozato
Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells...
October 4, 2016: Oncotarget
Bryan D Clifton, Pablo Librado, Shu-Dan Yeh, Edwin Solares, Daphne Real, Suvini Jayasekera, Wanting Zhang, Mijuan Shi, Ronni Park, Robert Magie, Hsiu-Ching Ma, Xiao-Qin Xia, Antonio Marco, Julio Rozas, José M Ranz
Gene clusters of recently duplicated genes are hotbeds for evolutionary change. However, our understanding of how mutational mechanisms and evolutionary forces shape the structural and functional evolution of these clusters is hindered by the high sequence identity among the copies, which typically results in their inaccurate representation in genome assemblies. The presumed testis-specific, chimeric gene Sdic originated and tandemly expanded in Drosophila melanogaster, contributing to increased male-male competition...
October 3, 2016: Molecular Biology and Evolution
Elias M Oziolor, Karel De Schamphelaere, Cole W Matson
The regulatory decision-making process regarding chemical safety is most often informed by evidence based on ecotoxicity tests that consider growth, reproduction and survival as end-points, which can be quantitatively linked to short-term population outcomes. Changes in these end-points resulting from chemical exposure can cause alterations in micro-evolutionary forces (mutation, drift, selection and gene flow) that control the genetic composition of populations. With multi-generation exposures, anthropogenic contamination can lead to a population with an altered genetic composition, which may respond differently to future stressors...
October 3, 2016: Ecotoxicology
Sudeesh Karumathil, Vijaya R Dirisala, Uthpala Srinadh, Valaboju Nikhil, N Satya Sampath Kumar, Rahul R Nair
Chaetognatha is a minor phylum, comprising transparent marine invertebrates varying in size from 0.5 to 12 cm. The exact phylogenetic position of Chaetognatha in Metazoa has not been deciphered as some embryological characteristics place chaetognaths among deuterostomes and some morphological characteristics place these among protostomes. In this study, the major factors that drive synonymous codon usage bias (SCUB) in the mitogenomes of representative species of Chaetognatha and chosen species of other closely related phyla were analyzed...
2016: Bioinformatics and Biology Insights
Evan J Myers, Aniko Marshall, Michael L Jennings, Mark D Parker
The SLC4A11 gene encodes the bicarbonate-transporter-related protein BTR1, which is mutated in syndromes characterized by vision and hearing loss. Signs of these diseases (congenital hereditary endothelial dystrophy (CHED) and Harboyan Syndrome) are evident in mouse models of Slc4a11 disruption. However, the intrinsic activity of Slc4a11 remains controversial, complicating assignment of its (patho)physiological role. Most studies concur that Slc4a11 transports H(+) (or the thermodynamically equivalent species OH(-)) rather than HCO3 (-) but disparities have arisen as to whether the transport is coupled to another species such as Na(+) or NH3/NH4 (+) Here for the first time, we examine the action of mouse Slc4a11 in Xenopus oocytes...
September 28, 2016: American Journal of Physiology. Cell Physiology
Matthew J Jenny, Samantha L Payton, David A Baltzegar, Jeffrey D Lozier
Mechanisms by which organisms genetically adapt to environmental conditions are of fundamental importance to studies of evolutionary biology and environmental physiology. Natural selection acts on existing genetic variation leading to adaptation through selection of new mutations that confer beneficial advantages to populations. The American oyster, Crassostrea virginica, is an excellent model to investigate interactions between environmental and ecological factors as driving forces for natural selection. A great example of this is represented by the diversity of C...
September 27, 2016: Journal of Molecular Evolution
Marcela Rosato, Aleš Kovařík, Ricardo Garilleti, Josep A Rosselló
Genes encoding ribosomal RNA (rDNA) are universal key constituents of eukaryotic genomes, and the nuclear genome harbours hundreds to several thousand copies of each species. Knowledge about the number of rDNA loci and gene copy number provides information for comparative studies of organismal and molecular evolution at various phylogenetic levels. With the exception of seed plants, the range of 45S rDNA locus (encoding 18S, 5.8S and 26S rRNA) and gene copy number variation within key evolutionary plant groups is largely unknown...
2016: PloS One
A Tazeen, N Afreen, M Abdullah, F Deeba, S H Haider, S N Kazim, S Ali, I H Naqvi, S Broor, A Ahmed, S Parveen
Dengue fever is an arthropod-borne viral infection that has become endemic in several parts of India including Delhi. We studied occurrence of co-infection with dengue viruses during an outbreak in New Delhi, India in 2014. For the present study, blood samples collected from symptomatic patients were analysed by RT-PCR. Eighty percent of the samples were positive for dengue virus. The result showed that DENV-1 (77%) was the predominant serotype followed by DENV-2 (60%). Concurrent infection with more than one serotype was identified in 43% of the positive samples...
September 13, 2016: Epidemiology and Infection
Deniz Akdis, Corinna Brunckhorst, Firat Duru, Ardan M Saguner
This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes...
August 2016: Arrhythmia & Electrophysiology Review
Robert J Robbins, Leonard Krishtalka, John C Wooley
BACKGROUND: Efforts to harmonize genomic data standards used by the biodiversity and metagenomic research communities have shown that prokaryotic data cannot be understood or represented in a traditional, classical biological context for conceptual reasons, not technical ones. RESULTS: Biology, like physics, has a fundamental duality-the classical macroscale eukaryotic realm vs. the quantum microscale microbial realm-with the two realms differing profoundly, and counter-intuitively, from one another...
2016: Standards in Genomic Sciences
Kamila Rachwał, Aleksandra Boguszewska, Joanna Kopcińska, Magdalena Karaś, Marek Tchórzewski, Monika Janczarek
Rhizobium leguminosarum bv. trifolii is capable of establishing a symbiotic relationship with plants from the genus Trifolium. Previously, a regulatory protein encoded by rosR was identified and characterized in this bacterium. RosR possesses a Cys2-His2-type zinc finger motif and belongs to Ros/MucR family of rhizobial transcriptional regulators. Transcriptome profiling of the rosR mutant revealed a role of this protein in several cellular processes, including the synthesis of cell-surface components and polysaccharides, motility, and bacterial metabolism...
2016: Frontiers in Microbiology
Baolei Yuan, Xingshun Wang, Chunyan Fan, Jin You, Yuchu Liu, Jason D Weber, Hanbing Zhongand, Yandong Zhang
The RNA helicase DHX33 has been shown to be a critical regulator of cell proliferation and growth. However, the underlying mechanisms behind DHX33 function remain incompletely understood. We present original evidence in multiple cell lines that DHX33 transcriptionally controls the expression of genes involved in cell cycle, notably cyclins, E2F1, CDCs and MCMs. DHX33 physically associates with the promoters of these genes and controls the loading of active RNA polymerase II onto these promoters. DHX33 deficiency abrogates cell cycle progression, DNA replication, and leads to cell apoptosis...
September 6, 2016: Molecular and Cellular Biology
Thomas Wicker, Yeisoo Yu, Georg Haberer, Klaus F X Mayer, Pradeep Reddy Marri, Steve Rounsley, Mingsheng Chen, Andrea Zuccolo, Olivier Panaud, Rod A Wing, Stefan Roffler
DNA (class 2) transposons are mobile genetic elements which move within their 'host' genome through excising and re-inserting elsewhere. Although the rice genome contains tens of thousands of such elements, their actual role in evolution is still unclear. Analysing over 650 transposon polymorphisms in the rice species Oryza sativa and Oryza glaberrima, we find that DNA repair following transposon excisions is associated with an increased number of mutations in the sequences neighbouring the transposon. Indeed, the 3,000 bp flanking the excised transposons can contain over 10 times more mutations than the genome-wide average...
2016: Nature Communications
Maria Lasalvia, Stefano Castellani, Palma D'Antonio, Giuseppe Perna, Annalucia Carbone, Anna Laura Colia, Angela Bruna Maffione, Vito Capozzi, Massimo Conese
The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module...
October 15, 2016: Experimental Cell Research
Rousselle Marjolaine, Faivre Nicolas, Ballenghien Marion, Galtier Nicolas, Nabholz Benoit
The fixation probability of a recessive beneficial mutation is increased on the X or Z chromosome, relative to autosomes, because recessive alleles carried by X or Z are exposed to selection in the heterogametic sex. This leads to an increased dN/dS ratio on sex chromosomes relative to autosomes, a pattern called the "fast-X" or "fast-Z" effect. Besides positive selection, the strength of genetic drift and the efficacy of purifying selection, which affect the rate of molecular evolution, might differ between sex chromosomes and autosomes...
September 1, 2016: Genome Biology and Evolution
Ying Li, Liyuan Lu, Juan Li
Hereditary spherocytosis is an inherited red blood cell membrane disorder resulting from mutations of genes encoding erythrocyte membrane and cytoskeletal proteins. Few equipments can observe the structural characteristics of hereditary spherocytosis directly expect for atomic force microscopy In our study, we proved atomic force microscopy is a powerful and sensitive instrument to describe the characteristics of hereditary spherocytosis. Erythrocytes from hereditary spherocytosis patients were small spheroidal, lacking a well-organized lattice on the cell membrane, with smaller cell surface particles and had reduced valley to peak distance and average cell membrane roughness vs...
September 2016: Cell Biochemistry and Biophysics
James A Loehr, Gary R Stinnett, Mayra Hernández-Rivera, Wesley T Roten, Lon J Wilson, Robia G Pautler, George G Rodney
KEY POINTS: Inhibiting Nox2 reactive oxygen species (ROS) production reduced in vivo calcium influx in dystrophic muscle. The lack of Nox2 ROS production protected against decreased in vivo muscle function in dystrophic mice. Manganese-enhanced magnetic resonance imaging (MEMRI) was able to detect alterations in basal calcium levels in skeletal muscle and differentiate disease status. Administration of Mn(2+) did not affect muscle function or the health of the animal, and Mn(2+) was cleared from skeletal muscle rapidly...
August 24, 2016: Journal of Physiology
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