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https://www.readbyqxmd.com/read/28640035/the-professionalism-and-integrity-in-research-program-description-and-preliminary-outcomes
#1
James M DuBois, John T Chibnall, Raymond Tait, Jillon S Vander Wal
Violations of rules and regulations in research can cause significant problems for human participants, animal subjects, data integrity, institutions, and investigators. The Professionalism and Integrity in Research Program (PI Program) provides remediation training that addresses the root causes of violations of rules and regulations in research. Through assessments, a three-day workshop, and follow-up coaching calls, the PI Program teaches evidence-based decision-making strategies designed to help researchers to compensate for bias, uncertainty, and work-related stress, and foster the skills needed to oversee research projects in today's complex regulatory environments...
June 20, 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28632130/the-laminar-organization-of-the-drosophila-ellipsoid-body-is-semaphorin-dependent-and-prevents-the-formation-of-ectopic-synaptic-connections
#2
Xiaojun Xie, Masashi Tabuchi, Matthew P Brown, Sarah P Mitchell, Mark N Wu, Alex L Kolodkin
The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons, and that early-developing EB neurons play an important regulatory role in EB laminae formation...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28624199/engineering-next-generation-bet-independent-mlv-vectors-for-safer-gene-therapy
#3
Sara El Ashkar, Dominique Van Looveren, Franziska Schenk, Lenard S Vranckx, Jonas Demeulemeester, Jan De Rijck, Zeger Debyser, Ute Modlich, Rik Gijsbers
Retroviral vectors have shown their curative potential in clinical trials correcting monogenetic disorders. However, therapeutic benefits were compromised due to vector-induced dysregulation of cellular genes and leukemia development in a subset of patients. Bromodomain and extraterminal domain (BET) proteins act as cellular cofactors that tether the murine leukemia virus (MLV) pre-integration complex to host chromatin via interaction with the MLV integrase (IN) and thereby define the typical gammaretroviral integration distribution...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622346/flavivirus-and-filovirus-evoprinters-new-alignment-tools-for-the-comparative-analysis-of-viral-evolution
#4
Thomas Brody, Amarendra S Yavatkar, Dong Sun Park, Alexander Kuzin, Jermaine Ross, Ward F Odenwald
BACKGROUND: Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest...
June 16, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28618157/liver-microsomal-lipid-enhances-the-activity-and-redox-coupling-of-co-localised-cytochrome-p450-reductase-cytochrome-p450-3a4-in-nanodiscs
#5
Kang-Cheng Liu, John M X Hughes, Sam Hay, Nigel S Scrutton
The haem-containing monooxygenase cytochrome P450 3A4 (CYP3A4) and its redox partner NADPH-dependent cytochrome P450 oxidoreductase (CPR) are among the most important enzymes in human liver for metabolising drugs and xenobiotic compounds. They are membrane-bound in the endoplasmic reticulum (ER). How ER co-localisation and the complex ER phospholipid composition influence enzyme activity are not well understood. CPR and CYP3A4 were incorporated into phospholipid bilayer nanodiscs, both singly, and together in a 1:1 ratio, to investigate the significance of membrane insertion and the influence of varying membrane composition on steady-state reaction kinetics...
June 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28610226/integrative-taxonomy-reveals-cryptic-diversity-in-neotropical-grasshoppers-taxonomy-phylogenetics-and-evolution-of-the-genus-i-sphenarium-i-charpentier-1842-orthoptera-pyrgomorphidae
#6
Salomón Sanabria-Urbán, Hojun Song, Ken Oyama, Antonio González-Rodríguez, Raúl Cueva Del Castillo
The genus Sphenarium Charpentier, 1842 comprises the most diverse group of the New World Pyrgomorphidae. These grasshoppers show an extensive variation in external morphology, and are culturally and economically important for Mexican people since pre-Hispanic times. Nevertheless, the taxonomy of Sphenarium has been chaotic and remained incompletely resolved until now. Following an integrative taxonomic framework, we infer the number of species in this genus by species delimitation based on morphological, phylogenetic, and geographic information...
June 8, 2017: Zootaxa
https://www.readbyqxmd.com/read/28607146/epigenetic-transcriptional-memory-of-gal-genes-depends-on-growth-in-glucose-and-the-tup1-transcription-factor-in-saccharomyces-cerevisiae
#7
Varun Sood, Ivelisse Cajigas, Agustina D'Urso, William H Light, Jason H Brickner
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2 and GAL7 These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory...
June 12, 2017: Genetics
https://www.readbyqxmd.com/read/28600887/therapeutic-effects-of-fgf23-c-tail-fc-in-a-murine-pre-clinical-model-of-x-linked-hypophosphatemia-via-the-selective-modulation-of-phosphate-reabsorption
#8
Kristen Johnson, Kymberly Levine, Joseph Sergi, Jean Chamoun, Rachel Roach, Jackie Vekich, Mike Favis, Mark Horn, Xianjun Cao, Brian Miller, William Snyder, Dikran Aivazian, William Reagan, Edwin Berryman, Jennifer Colangelo, Victoria Markiewicz, Cedo Bagi, Thomas P Brown, Anthony Coyle, Moosa Mohammadi, Jeanne Magram
Fibroblast growth factor 23 (FGF23) is the causative factor of X-linked hypophosphatemia (XLH), a genetic disorder effecting 1:20,000 that is characterized by excessive phosphate excretion, elevated FGF23 levels and a rickets/osteomalacia phenotype. FGF23 inhibits phosphate reabsorption and suppresses 1α,25-dihydroxyvitamin D (1,25D) biosynthesis, analytes that differentially contribute to bone integrity and deleterious soft tissue mineralization. As inhibition of ligand broadly modulates downstream targets, balancing efficacy and unwanted toxicity is difficult when targeting the FGF23 pathway...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28592807/reconstruction-of-complex-directional-networks-with-group-lasso-nonlinear-conditional-granger-causality
#9
Guanxue Yang, Lin Wang, Xiaofan Wang
Reconstruction of networks underlying complex systems is one of the most crucial problems in many areas of engineering and science. In this paper, rather than identifying parameters of complex systems governed by pre-defined models or taking some polynomial and rational functions as a prior information for subsequent model selection, we put forward a general framework for nonlinear causal network reconstruction from time-series with limited observations. With obtaining multi-source datasets based on the data-fusion strategy, we propose a novel method to handle nonlinearity and directionality of complex networked systems, namely group lasso nonlinear conditional granger causality...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591182/an-integrated-calcium-imaging-processing-toolbox-for-the-analysis-of-neuronal-population-dynamics
#10
Sebastián A Romano, Verónica Pérez-Schuster, Adrien Jouary, Jonathan Boulanger-Weill, Alessia Candeo, Thomas Pietri, Germán Sumbre
The development of new imaging and optogenetics techniques to study the dynamics of large neuronal circuits is generating datasets of unprecedented volume and complexity, demanding the development of appropriate analysis tools. We present a comprehensive computational workflow for the analysis of neuronal population calcium dynamics. The toolbox includes newly developed algorithms and interactive tools for image pre-processing and segmentation, estimation of significant single-neuron single-trial signals, mapping event-related neuronal responses, detection of activity-correlated neuronal clusters, exploration of population dynamics, and analysis of clusters' features against surrogate control datasets...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28587660/recommendations-for-cerebrospinal-fluid-collection-for-the-analysis-by-elisa-of-neurogranin-trunc-p75-%C3%AE-synuclein-and-total-tau-in-combination-with-a%C3%AE-1-42-a%C3%AE-1-40
#11
Hugo Vanderstichele, Leentje Demeyer, Shorena Janelidze, Els Coart, Erik Stoops, Kimberley Mauroo, Victor Herbst, Cindy François, Oskar Hansson
BACKGROUND: The pathophysiology of neurodegeneration is complex. Its diagnosis requires an early identification of sequential changes in several hallmarks in the brains of affected subjects. The presence of brain pathology can be visualized in the cerebrospinal fluid (CSF) by protein profiling. It is clear that the field of Alzheimer's disease (AD) will benefit from an integration of algorithms including CSF concentrations of individual proteins, especially as an aid in clinical decision-making or to improve patient enrolment in clinical trials...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28584084/logical-modeling-of-lymphoid-and-myeloid-cell-specification-and-transdifferentiation
#12
Samuel Collombet, Chris van Oevelen, Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di Stefano, Morgane Thomas-Chollier, Thomas Graf, Denis Thieffry
Blood cells are derived from a common set of hematopoietic stem cells, which differentiate into more specific progenitors of the myeloid and lymphoid lineages, ultimately leading to differentiated cells. This developmental process is controlled by a complex regulatory network involving cytokines and their receptors, transcription factors, and chromatin remodelers. Using public data and data from our own molecular genetic experiments (quantitative PCR, Western blot, EMSA) or genome-wide assays (RNA-sequencing, ChIP-sequencing), we have assembled a comprehensive regulatory network encompassing the main transcription factors and signaling components involved in myeloid and lymphoid development...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28575120/structural-basis-for-5-ets-recognition-by-utp4-at-the-early-stages-of-ribosome-biogenesis
#13
Fabiola R Calviño, Markus Kornprobst, Géza Schermann, Fabienne Birkle, Klemens Wild, Tamas Fischer, Ed Hurt, Yasar Luqman Ahmed, Irmgard Sinning
Eukaryotic ribosome biogenesis begins with the co-transcriptional assembly of the 90S pre-ribosome. The 'U three protein' (UTP) complexes and snoRNP particles arrange around the nascent pre-ribosomal RNA chaperoning its folding and further maturation. The earliest event in this hierarchical process is the binding of the UTP-A complex to the 5'-end of the pre-ribosomal RNA (5'-ETS). This oligomeric complex predominantly consists of β-propeller and α-solenoidal proteins. Here we present the structure of the Utp4 subunit from the thermophilic fungus Chaetomium thermophilum at 2...
2017: PloS One
https://www.readbyqxmd.com/read/28572580/uropa-a-tool-for-universal-robust-peak-annotation
#14
Maria Kondili, Annika Fust, Jens Preussner, Carsten Kuenne, Thomas Braun, Mario Looso
The annotation of genomic ranges of interest represents a recurring task for bioinformatics analyses. These ranges can originate from various sources, including peaks called for transcription factor binding sites (TFBS) or histone modification ChIP-seq experiments, chromatin structure and accessibility experiments (such as ATAC-seq), but also from other types of predictions that result in genomic ranges. While peak annotation primarily driven by ChiP-seq was extensively explored, many approaches remain simplistic ("most closely located TSS"), rely on fixed pre-built references, or require complex scripting tasks on behalf of the user...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28559158/tissue-and-cellular-biomechanics-during-corneal-wound-injury-and-repair
#15
Vijay Krishna Raghunathan, Sara M Thomasy, Peter Strøm, Bernardo Yañez-Soto, Shaun P Garland, Jasmyne Sermeno, Christopher M Reilly, Christopher J Murphy
Corneal wound healing is an enormously complex process that requires the simultaneous cellular integration of multiple soluble biochemical cues, as well as cellular responses to the intrinsic chemistry and biophysical attributes associated with the matrix of the wound space. Here, we document how the biomechanics of the corneal stroma are altered through the course of wound repair following keratoablative procedures in rabbits. Further we documented the influence that substrate stiffness has on stromal cell mechanics...
May 27, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28551818/novel-three-dimensional-image-fusion-software-to-facilitate-guidance-of-complex-cardiac-catheterization-3d-image-fusion-for-interventions-in-chd
#16
Sebastian Goreczny, Pawel Dryzek, Gareth J Morgan, Maciej Lukaszewski, Jadwiga A Moll, Tomasz Moszura
We report initial experience with novel three-dimensional (3D) image fusion software for guidance of transcatheter interventions in congenital heart disease. Developments in fusion imaging have facilitated the integration of 3D roadmaps from computed tomography or magnetic resonance imaging datasets. The latest software allows live fusion of two-dimensional (2D) fluoroscopy with pre-registered 3D roadmaps. We reviewed all cardiac catheterizations guided with this software (Philips VesselNavigator). Pre-catheterization imaging and catheterization data were collected focusing on fusion of 3D roadmap, intervention guidance, contrast and radiation exposure...
May 27, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28551477/an-evaluation-of-approaches-used-to-teach-quality-improvement-to-pre-registration-healthcare-professionals-an-integrative-review
#17
REVIEW
Lorraine Armstrong, Ashley Shepherd, Fiona Harris
BACKGROUND: Improving the quality of healthcare remains central to UK and international policy, practice and research. In 2003, The Institute of Medicine's 'Health Professions Education: A Bridge to Quality', advocated quality improvement as a core competency for all healthcare professionals. As a result, developing capacity and capability of those applying improvement methodologies in the pre-registration population has risen, yet, little is known about the teaching approaches employed for this purpose...
May 22, 2017: International Journal of Nursing Studies
https://www.readbyqxmd.com/read/28545431/structured-feedback-on-students-concept-maps-the-proverbial-path-to-learning
#18
Conran Joseph, David Conradsson, Lena Nilsson Wikmar, Michael Rowe
BACKGROUND: Good conceptual knowledge is an essential requirement for health professions students, in that they are required to apply concepts learned in the classroom to a variety of different contexts. However, the use of traditional methods of assessment limits the educator's ability to correct students' conceptual knowledge prior to altering the educational context. Concept mapping (CM) is an educational tool for evaluating conceptual knowledge, but little is known about its use in facilitating the development of richer knowledge frameworks...
May 25, 2017: BMC Medical Education
https://www.readbyqxmd.com/read/28528380/the-rat-corticospinal-system-is-functionally-and-anatomically-segregated
#19
Rafael Olivares-Moreno, Yunuen Moreno-Lopez, Luis Concha, Guadalupe Martínez-Lorenzana, Miguel Condés-Lara, Matilde Cordero-Erausquin, Gerardo Rojas-Piloni
The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord...
May 20, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28526435/the-bidirectional-gut-brain-microbiota-axis-as-a-potential-nexus-between-traumatic-brain-injury-inflammation-and-disease
#20
Mark H Sundman, Nan-Kuei Chen, Vignesh Subbian, Ying-Hui Chou
As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS)...
May 17, 2017: Brain, Behavior, and Immunity
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