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https://www.readbyqxmd.com/read/29909429/task-set-control-chunking-and-hierarchical-timing-in-rhythm-production
#1
Lars D Hestermann, Johan Wagemans, Ralf T Krampe
We investigated task-set control processes and chunking in 16 novices and 16 amateur musicians, who produced unimanual rhythms in three experimental conditions: low-level timing tasks required isochronous tapping at constant target durations; sequencing tasks consisted of individual rhythmic patterns comprising multiple target durations; the task-set control condition required alternations between two rhythmic patterns. According to our hierarchical timing control model conditions differed in their task-set control demands necessary to provide rhythm programs for the sequencing of individual intervals...
June 16, 2018: Psychological Research
https://www.readbyqxmd.com/read/29909059/mir-383-negatively-regulates-osteoblastic-differentiation-of-bone-marrow-mesenchymal-stem-cells-in-rats-by-targeting-satb2
#2
Jianfei Tang, Zeng Zhang, Xiangyun Jin, Huipeng Shi
Emerging evidence indicates that microRNAs (miRNAs, miRs) play diverse roles in the regulation of biological processes, including osteoblastic differentiation. In this study, we found that miR-383 is a critical regulator of osteoblastic differentiation. We showed that miR-383 was downregulated during osteoblastic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). Overexpression of miR-383 suppressed osteoblastic differentiation of BMSCs by downregulating alkaline phosphatase (ALP), matrix mineralization, and mRNA and protein levels of RUNX2 and OCN, whereas a knockdown of miR-383 promoted osteoblastic differentiation in vitro...
June 14, 2018: Bone
https://www.readbyqxmd.com/read/29909007/early-emergence-of-de-novo-egfr-t790-m-gatekeeper-mutations-during-erlotinib-treatment-in-pc9-non-small-cell-lung-cancer-cells
#3
Sujin Kim, Angela Kj Park, Jeonghee Cho
The emergence of the T790 M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) gene is an important mechanism that can lead to the acquired resistance to EGFR-targeted tyrosine kinase inhibitors such as erlotinib or gefitinib. These drugs have been used in treating a subset of non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. Here we investigated the paths leading to the acquisition of the T790 M mutation by establishing an erlotinib resistant PC9 cell model harboring ectopically introduced EGFR cDNA...
June 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29908837/expression-of-agpat2-an-enzyme-involved-in-the-glycerophospholipid-triacylglycerol-biosynthesis-pathway-is-directly-regulated-by-hif-1-and-promotes-survival-and-etoposide-resistance-of-cancer-cells-under-hypoxia
#4
Eleni-Anastasia Triantafyllou, Eleni Georgatsou, Ilias Mylonis, George Simos, Efrosyni Paraskeva
Hypoxia inducible factor-1 (HIF-1) supports survival of normal cells under low oxygen concentration and cancer cells in the hypoxic tumor microenvironment. This involves metabolic reprogramming via upregulation of glycolysis, downregulation of oxidative phosphorylation and, less well documented, effects on lipid metabolism. To investigate the latter, we examined expression of relevant enzymes in cancer cells grown under hypoxia. We show that expression of acylglycerol-3-phosphate acyltransferase 2 (AGPAT2), also known as lysophosphatidic acid acyltransferase β (LPAATβ), was upregulated under hypoxia and this was impaired by siRNA-mediated knockdown of HIF-1α...
June 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29908491/go-with-the-flow-or-solitary-confinement-a-look-inside-the-single-cell-toolbox-for-isolation-of-rare-and-uncultured-microbes
#5
REVIEW
Geert Rb Huys, Jeroen Raes
With the vast majority of the microbial world still considered unculturable or undiscovered, microbiologists not only require more fundamental insights concerning microbial growth requirements but also need to implement miniaturized, versatile and high-throughput technologies to upscale current microbial isolation strategies. In this respect, single-cell-based approaches are increasingly finding their way to the microbiology lab. A number of recent studies have demonstrated that analysis and separation of free microbial cells by flow-based sorting as well as physical stochastic confinement of individual cells in microenvironment compartments can facilitate the isolation of previously uncultured species and the discovery of novel microbial taxa...
June 13, 2018: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29908157/a-novel-electrochemical-dna-biosensor-for-ebola-virus-detection
#6
Hoda Ilkhani, Siamak Farhad
The aim of this study was to fabricate a novel electrochemical-based DNA-sensing device for Ebola virus DNA diagnostic by an enzyme-amplified detection, which improves the sensitivity and selectivity of the sensor. A thiolated DNA capture probe sequence was immobilized on the screen printed electrode surface and hybridized with biotinylated target strand DNA for the fabrication of Ebola DNA-sensing devices. Prior to the electrochemical detection of the enzymatic product by differential pulse voltammetry (DPV) method, the biotinylated hybrid was labelled with a streptavidin-alkaline phosphate conjugate on the surface of the working electrode...
June 13, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29908151/vaccination-with-a-cd4-and-cd8-t-cell-epitopes-based-recombinant-chimeric-protein-derived-from-leishmania-infantum-proteins-confers-protective-immunity-against-visceral-leishmaniasis
#7
Daniel S Dias, Patrícia A F Ribeiro, Vívian T Martins, Daniela P Lage, Lourena E Costa, Miguel A Chávez-Fumagalli, Fernanda F Ramos, Thaís T O Santos, Fernanda Ludolf, Jamil S Oliveira, Tiago A O Mendes, Eduardo S Silva, Alexsandro S Galdino, Mariana C Duarte, Bruno M Roatt, Daniel Menezes-Souza, Antonio L Teixeira, Eduardo A F Coelho
Vaccination seems to be the best approach to control visceral leishmaniasis (VL). Resistance against infection is based on the development of a Th1 immune response characterized by the production of interferons-γ (IFN-γ), interleukin-12 (IL-12), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), among others. A number of antigens have been tested as potential targets against the disease; few of them are able to stimulate human immune cells. In the present study, 1 prediction of MHC class I and II molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide repeat-containing proteins, was performed using bioinformatics tools, and a T-cell epitopes-based recombinant chimeric protein was constructed, synthetized and purified to be evaluated in invitro and in vivo experiments...
May 22, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29908130/designed-macrocyclic-peptides-as-nanomolar-amyloid-inhibitors-based-on-minimal-recognition-elements
#8
Anna Spanopoulou, Luzia Heidrich, Hong-Ru Chen, Christina Frost, Dean Hrle, Eleni Malideli, Kathleen Hille, Alexandros Grammatikopoulos, Jürgen Bernhagen, Martin Zacharias, Gerhard Rammes, Aphrodite Kapurniotu
Amyloid self-assembly is linked to the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), but so far none of the anti-amyloid molecules has reached the clinic. Macrocyclic peptides belong to the most attractive drug candidates. Here we present macrocyclic peptides (MCIPs) designed using minimal IAPP-derived recognition elements as a novel class of nanomolar amyloid inhibitors of both Abeta40(42) and IAPP or Abeta40(42) alone and show that chirality controls inhibitor selectivity. Sequence optimization led to the discovery of an Abeta40(42)-selective MCIP exhibiting high proteolytic stability in human plasma and human blood-brain-barrier (BBB) crossing ability in a cell model, two highly desirable properties for anti-amyloid drugs in AD...
June 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29908121/pathological-manifestations-of-farber-disease-in-a-new-mouse-model
#9
Nadine Beckmann, Stephanie Kadow, Fabian Schumacher, Joachim R Göthert, Stefanie Kesper, Annette Draeger, Walter J Schulz-Schaeffer, Jiang Wang, Jan U Becker, Melanie Kramer, Claudine Kühn, Burkhard Kleuser, Katrin Anne Becker, Erich Gulbins
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of Farber Disease is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of Farber Disease and ceramide accumulation. Asah1tmEx1 mice were generated by deletion of the acid ceramidase signal peptide sequence...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29907982/results-of-next-generation-sequencing-gene-panel-diagnostics-including-copy-number-variation-analysis-in-810-patients-suspected-of-heritable-thoracic-aortic-disorders
#10
Eline Overwater, Luisa Marsili, Marieke J H Baars, Annette F Baas, Irma van de Beek, Eelco Dulfer, Johanna M van Hagen, Yvonne Hilhorst-Hofstee, Marlies Kempers, Ingrid P Krapels, Leonie A Menke, Judith M A Verhagen, Kak K Yeung, Petra J G Zwijnenburg, Maarten Groenink, Peter van Rijn, Marjan M Weiss, Els Voorhoeve, J Peter van Tintelen, Arjan C Houweling, Alessandra Maugeri
Simultaneous analysis of multiple genes using next generation sequencing (NGS) technology has become widely available. Copy number variations (CNVs) in disease-associated genes have emerged as a cause for several hereditary disorders. CNVs are, however, not routinely detected using NGS analysis. The aim of this study was to assess the diagnostic yield and the prevalence of CNVs using our panel of Hereditary Thoracic Aortic Disease (H-TAD) associated genes. 810 patients suspected of H-TAD were analysed by targeted NGS analysis of 21 H-TAD associated genes...
June 16, 2018: Human Mutation
https://www.readbyqxmd.com/read/29907962/prenatal-diagnosis-of-skeletal-dysplasias-using-a-targeted-skeletal-gene-panel
#11
Xinyao Zhou, Natalie Chandler, Linbei Deng, Jia Zhou, Meizhen Yuan, Luming Sun
OBJECTIVE: This study aimed to perform an accurate and precise diagnosis for foetuses with suspected skeletal anomalies based on an incomplete and limited ultrasound phenotype. METHODS: Proband-only targeted skeletal gene panel sequencing was performed on twelve families who had foetuses with suspected skeletal anomalies based on ultrasound evaluations at a mean gestational age of 24 weeks and 3 days. The foetuses all had normal standard genetic testing yield (karyotyping and microarray)...
June 15, 2018: Prenatal Diagnosis
https://www.readbyqxmd.com/read/29907874/nearing-saturation-of-cancer-driver-gene-discovery
#12
EDITORIAL
David Hsiehchen, Antony Hsieh
Extensive sequencing efforts of cancer genomes such as The Cancer Genome Atlas (TCGA) have been undertaken to uncover bona fide cancer driver genes which has enhanced our understanding of cancer and revealed therapeutic targets. However, the number of driver gene mutations is bounded, indicating that there must be a point when further sequencing efforts will be excessive. We found that there was a significant positive correlation between sample size and identified driver gene mutations across 33 cancers sequenced by the TCGA, which is expected if additional sequencing is still leading to the identification of more driver genes...
June 15, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29907859/the-microrna-10a-id3-runx2-axis-modulates-the-development-of-ossification-of-posterior-longitudinal-ligament
#13
Chen Xu, Hao Zhang, Wei Gu, Huiqiao Wu, Yuanyuan Chen, Wenchao Zhou, Baifeng Sun, Xiaolong Shen, Zicheng Zhang, Yue Wang, Yang Liu, Wen Yuan
Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29907799/utility-and-limitations-of-exome-sequencing-as-a-genetic-diagnostic-tool-for-children-with-hearing-loss
#14
Sarah Sheppard, Sawona Biswas, Mindy H Li, Vijayakumar Jayaraman, Ian Slack, Edward J Romasko, Ariella Sasson, Joshua Brunton, Ramakrishnan Rajagopalan, Mahdi Sarmady, Jenica L Abrudan, Sowmya Jairam, Elizabeth T DeChene, Xiahoan Ying, Jiwon Choi, Alisha Wilkens, Sarah E Raible, Maria I Scarano, Avni Santani, Jeffrey W Pennington, Minjie Luo, Laura K Conlin, Batsal Devkota, Matthew C Dulik, Nancy B Spinner, Ian D Krantz
PURPOSE: Hearing loss (HL) is the most common sensory disorder in children. Prompt molecular diagnosis may guide screening and management, especially in syndromic cases when HL is the single presenting feature. Exome sequencing (ES) is an appealing diagnostic tool for HL as the genetic causes are highly heterogeneous. METHODS: ES was performed on a prospective cohort of 43 probands with HL. Sequence data were analyzed for primary and secondary findings. Capture and coverage analysis was performed for genes and variants associated with HL...
June 15, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29907797/a-comprehensive-iterative-approach-is-highly-effective-in-diagnosing-individuals-who-are-exome-negative
#15
Vandana Shashi, Kelly Schoch, Rebecca Spillmann, Heidi Cope, Queenie K-G Tan, Nicole Walley, Loren Pena, Allyn McConkie-Rosell, Yong-Hui Jiang, Nicholas Stong, Anna C Need, David B Goldstein
PURPOSE: Sixty to seventy-five percent of individuals with rare and undiagnosed phenotypes remain undiagnosed after exome sequencing (ES). With standard ES reanalysis resolving 10-15% of the ES negatives, further approaches are necessary to maximize diagnoses in these individuals. METHODS: In 38 ES negative patients an individualized genomic-phenotypic approach was employed utilizing (1) phenotyping; (2) reanalyses of FASTQ files, with innovative bioinformatics; (3) targeted molecular testing; (4) genome sequencing (GS); and (5) conferring of clinical diagnoses when pathognomonic clinical findings occurred...
June 15, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29907756/correction-cost-of-cancer-diagnosis-using-next-generation-sequencing-targeted-gene-panels-in-routine-practice-a-nationwide-french-study
#16
Patricia Marino, Rajae Touzani, Lionel Perrier, Etienne Rouleau, Dede Sika Kossi, Zou Zhaomin, Nathanaël Charrier, Nicolas Goardon, Claude Preudhomme, Isabelle Durand-Zaleski, Isabelle Borget, Sandrine Baffert
Since the publication of the article, it has been noted that there is an error in Table 2. Where 543€ is listed in the final column of the table, this should have been written as 550€.
June 15, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29907308/advanced-editing-of-the-nuclear-and-plastid-genomes-in-plants
#17
Agnieszka A Piatek, Scott C Lenaghan, C Neal Stewart
Genome editing is a powerful suite of technologies utilized in basic and applied plant research. Both nuclear and plastid genomes have been genetically engineered to alter traits in plants. While the most frequent molecular outcome of gene editing has been knockouts resulting in a simple deletion of an endogenous protein of interest from the host's proteome, new genes have been added to plant genomes and, in several instances, the sequence of endogenous genes have been targeted for a few coding changes. Targeted plant characteristics for genome editing range from single gene targets for agronomic input traits to metabolic pathways to endow novel plant function...
August 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29907144/a-rare-chd5-haplotype-and-its-interactions-with-environmental-factors-predicting-hepatocellular-carcinoma-risk
#18
Qin Xiao, Lianzhou Chen, Haiqing Luo, Hongmei Li, Qingming Kong, Fei Jiao, Shifeng Pang, Ming Zhang, Feifei Lan, Wenguo Fan, Hui Luo, Tao Tao, Xiao Zhu
BACKGROUND: CHD5 is a conventional tumour-suppressing gene in many tumours. The aim of this study was to determine whether CHD5 variants contribute to the risk of hepatocellular carcinoma (HCC). METHODS: Gene variants were identified using next-generation sequencing targeted on referenced mutations followed by TaqMan genotyping in two case-control studies. RESULTS: We discovered a rare variant (haplotype AG) in CHD5 (rs12564469-rs9434711) that was markedly associated with the risk of HCC in a Chinese population...
June 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29906997/diffusion-modulation-of-dna-by-toehold-exchange
#19
Thanapop Rodjanapanyakul, Fumi Takabatake, Keita Abe, Ibuki Kawamata, Shinichiro M Nomura, Satoshi Murata
We propose a method to control the diffusion speed of DNA molecules with a target sequence in a polymer solution. The interaction between solute DNA and diffusion-suppressing DNA that has been anchored to a polymer matrix is modulated by the concentration of the third DNA molecule called the competitor by a mechanism called toehold exchange. Experimental results show that the sequence-specific modulation of the diffusion coefficient is successfully achieved. The diffusion coefficient can be modulated up to sixfold by changing the concentration of the competitor...
May 2018: Physical Review. E
https://www.readbyqxmd.com/read/29906635/learning-of-goal-relevant-and-irrelevant-complex-visual-sequences-in-human-v1
#20
Clive R Rosenthal, Indira Mallik, Cesar Caballero-Gaudes, Martin I Sereno, David Soto
Learning and memory are supported by a network involving the medial temporal lobe and linked neocortical regions. Emerging evidence indicates that primary visual cortex (i.e., V1) may contribute to recognition memory, but this has been tested only with a single visuospatial sequence as the target memorandum. The present study used functional magnetic resonance imaging to investigate whether human V1 can support the learning of multiple, concurrent, and complex visual sequences involving discontinous (second-order) associations...
June 12, 2018: NeuroImage
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