bluuebunny/crossref_metadata_2025_split huggingface dataset:
Australian Nurses' Knowledge of Pressure Injury Prevention and Management
Authors: Fulbrook Paul , Lawrence Petra , Miles Sandra 
Published: February 2019

PURPOSE:The aim of this study was to assess nurses' knowledge of pressure injuries in order to gather benchmark data, identify knowledge gaps, and based on results, implement educational strategies to improve practice.DESIGN:Cross-sectional survey.SUBJECTS AND SETTING:The study setting was a large Australian tertiary general hospital employing approximately 2500 nurses in both full-time and part-time roles. A proportional sample (25%) stratified by experience, preparation, and facility-generated categories (nursing grade) was generated. The sample included nursing students and nursing assistants. Three hundred six participants completing the survey.INSTRUMENT:The Pieper-Zulkowski Pressure Ulcer Knowledge Test (PZPUKT) version 2, comprising 72 statements, with 3 subscales (prevention/risk, staging, and wound description) was used to measure pressure injury knowledge. Item responses are “True,” “False,” and “Don't know.” For the purpose of analyses, correct responses were scored 1, and incorrect or “don't know” responses were scored 0. Generally accepted ranges of scoring for the original PZPUKT specify less than 70% as unsatisfactory, 70% to 79.9% as satisfactory, 80% to 89.9% as good, and 90% and greater as very good knowledge of pressure injury prevention.METHODS:The survey was advertised throughout the hospital by strategically placed posters, computer screen savers within the hospital, and e-mails. Respondents completed paper-based questionnaires and data were manually entered online. Data were collected between September 2015 and October 2016. Descriptive and nonparametric inferential statistical tests (Mann-WhitneyU, Kruskal-WallisH) were used to analyze within sample differences in scores.RESULTS:The overall mean knowledge score was 65%; approximately two-thirds of the sample (68%) scored 60% and greater, reflecting an unsatisfactory knowledge level of pressure injury prevention according to the original PZPUKT scores. The lowest mean scores were found in the “wound description” subscale. Participants who sought pressure injury information via the Internet or had read pressure injury guidelines scored significantly higher than those who did not (P= .001 andP< .001, respectively). Seventeen items were answered incorrectly by over half of participants, identifying important knowledge deficits, particularly within the wound description subscale.CONCLUSIONS:When compared with results from studies using the PZPUKT, we contend that a cutoff score of 60% and greater (instead of ≥70%) should be used to indicate an overall satisfactory score. Our results identified deficits in pressure injury knowledge related to seating support and seated individuals and wound dressings as areas where nurses would benefit from focused education strategies.
Molecular architecture of a membrane-spanning hormone acyltransferase required for metabolic regulation
Authors: Campaña Maria B. , Irudayanathan Flaviyan Jerome , Davis Tasha R. , McGovern-Gooch Kayleigh R. , Loftus Rosemary , Ashkar Mohammad , Escoffery Najae , Navarro Melissa , Sieburg Michelle A. , Nangia Shikha , Hougland James L. 
Published: February 2019

AbstractIntegral membrane proteins represent a large and essential portion of the proteome that often prove challenging for structural studies. We demonstrate a synergistic approach to structurally model topologically complex integral membrane proteins by combining co-evolutionary constraints and computational modeling with biochemical validation. We report the first structural model of a eukaryotic membrane-bound O-acyltransferase (MBOAT), ghrelin O-acyltransferase (GOAT), which modifies the metabolism-regulating hormone ghrelin. Our structure suggests an unanticipated strategy for trans-membrane protein acylation, with catalysis occurring in an internal channel as GOAT acts as an “enzyme inside a pore”. Our structure opens the door to structure-guided inhibitor design targeting GOAT and other MBOAT family members while validating the power of our approach to generate predictive structural models for other experimentally challenging integral membrane proteins.
Population responses of naïve roe deer to the recolonization of the French Vercors by wolves
Authors: Randon M , Bonenfant C , Michallet J , Chevrier T , Toïgo C , Gaillard J-M , Valeix M 
Published: February 2019

AbstractIn a context of rapidly changing carnivore populations worldwide, it is crucial to understand the consequences of these changes for prey populations. The recolonization by wolves of the French Vercors mountain range and the long-term monitoring (2001-2017) of roe deer populations provided us a unique opportunity to assess both lethal and non-lethal effects of wolves on these populations. We compared roe deer population abundance and growth, fawn body mass, and browsing intensity in two contrasted areas: a central area (core of a wolf pack territory characterized by an intense use by wolves) and a peripheral area (used more occasionally). Both populations of roe deer strongly dropped after an extremely severe winter but the population of the central area facing with wolves was slower to recover (due to a much lower growth rate the following year) and remained at lower abundance levels for 5 years. Fawn body mass was lower in the central area during that period and was not influenced by weather conditions or population abundance. The browsing index in the forests in presence of wolves decreased for a longer period, suggesting that possible habitat shifts have occurred. Altogether, the effects of wolves on the roe deer population in the central area occurred mainly during a 5-year period following the establishment of wolves, with effects at the population level in the first years only through the interplay between wolf predation (before wolves started preying on red deer), harsh winter conditions and naïveté of prey to this recolonizing predator.
Latent Mycobacterium tuberculosis infection provides protection for the host by changing the activation state of the innate immune system
Authors: Nemeth Johannes , Olson Gregory S. , Rothchild Alissa , Jahn Ana , Mai Dat , Duffy Fergal , Delahaye Jared , Srivatsan Sanjay , Plumlee Courtney , Urdahl Kevin , Gold Elizabeth , Diercks Alan , Aderem Alan 
Published: February 2019

AbstractAn efficacious vaccine against adult tuberculosis (TB) remains elusive. Progress is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of TB1. Over 90% of people who become infected with Mtb mount an immune response that contains the bacteria indefinitely, leading to a state known as “latent TB infection” (LTBI)2. A significant body of epidemiologic evidence indicates that LTBI protects against active TB after re-exposure, offering an intriguing avenue to identifying protective mechanisms3, 4. We show that in a mouse model, LTBI is highly protective against infection with Mtb for up to 100 days following aerosol challenge. LTBI mice are also protected against heterologous bacterial challenge (Listeria monocytogenes) and disseminated melanoma suggesting that protection is in part mediated by alterations in the activation state of the innate immune system. Protection is associated with elevated activation of alveolar macrophages (AM), the first cells that respond to inhaled Mtb, and accelerated recruitment of Mtb-specific T cells to the lung parenchyma upon aerosol challenge. Systems approaches, including transcriptome analysis of both naïve and infected AMs, as well as ex vivo functional assays, demonstrate that LTBI reconfigures the response of tissue resident AMs.. Furthermore, we demonstrate that both LTBI mice and latently infected humans show similar alterations in the relative proportions of circulating innate immune cells, suggesting that the same cellular changes observed in the LTBI mouse model are also occurring in humans. Therefore, we argue that under certain circumstances, LTBI could be beneficial to the host by providing protection against subsequent Mtb exposure.
De novo compartment deconvolution and weight estimation of tumor samples (DECODER)
Authors: Peng Xianlu Laura , Moffitt Richard A , Torphy Robert J , Volmar Keith E , Yeh Jen Jen 
Published: February 2019

AbstractTumors are mixtures of different compartments. While global gene expression analysis profiles the average expression of all compartments in a sample, identifying the specific contribution of each compartment remains a challenge. With the increasing recognition of the importance of non-neoplastic components, the ability to breakdown the gene expression contribution of each is critical. To this end, we developed DECODER, an integrated framework which performs de novo deconvolution, and compartment weight estimation for a single sample. We use DECODER to deconvolve 33 TCGA tumor RNA-seq datasets and show that it may be applied to other data types including ATAC-seq. We demonstrate that it can be utilized to reproducibly estimate cellular compartment weights in pancreatic cancer that are clinically meaningful. Application of DECODER across cancer types advances the capability of identifying cellular compartments in an unknown sample and may have implications for identifying the tumor of origin for cancers of unknown primary.
A new pathway of pre-tRNA surveillance in yeast
Authors: Payea Matthew J. , De Zoysa Thareendra C. , Phizicky Eric M. 
Published: February 2019

ABSTRACTDuring tRNA maturation in yeast, aberrant pre-tRNAs are targeted for 3’-5’ degradation by the nuclear surveillance pathway, and mature tRNAs are targeted for 5’-3’ degradation by the rapid tRNA decay (RTD) pathway, due to lack of certain body modifications or to destabilizing mutations. Here we show that the RTD pathway also targets pre-tRNAs through an unknown, but distinct, mechanism that occurs after nuclear export. Anticodon stem RTD variants of both tRNATyrand tRNASer(CGA)are substrates for pre-tRNA RTD, triggered by the accumulation of end-matured unspliced pre-tRNA due to altered secondary structure of the region comprising the anticodon stem-loop and the intron. Furthermore, increased nuclear availability of a pre-tRNA RTD substrate can provoke decay by nuclear surveillance. We interpret these results in terms of a model of opportunistic tRNA decay, wherein tRNAs are degraded due to a combination of structural instability and increased availability to decay pathways.
Molecular Dynamics Simulations of Glycosaminoglycan Oligosaccharide Using Newer Force Fields
Authors: Nagarajan Balaji , Sankaranarayanan Nehru Viji , Desai Umesh R. 
Published: February 2019

AbstractHeparin/heparan sulfate (H/HS) are ubiquitous biopolymers that interact with many proteins to induce myriad biological functions. It is critical to understand conformational properties of H/HS in solution so as to identify their preferred protein targets. Unfortunately, the massive heterogeneity of H/HS precludes the use of solution-based experimental techniques for the thousands of sequences that occur in nature. Computational simulations offer an attractive alternative and several all-atom force fields have been developed to understand their conformational properties. Recently, CHARMM36 carrying parameters forN-sulfamate was developed. This work compares molecular dynamics simulations of a hexasaccharide (HS06) using two all-atom force fields – CHARMM36 and GLYCAM06. We also introduce two new straightforward parameters, including end-to-end distance and minimum volume enclosing ellipsoid, to understand the conformational behavior of HS06. In addition, we analyzed inter- and intra-molecular hydrogen bonds and intermediate water bridges formed for HS06 using both force fields. Overall, CHARMM36 and GLYCAM06 gave comparable results, despite few, small differences. The MD simulations show that HS06 samples a range of conformations in solution with more than one nearly equivalent global minima, which contrasts with the assumed single conformation conclusion derived on the basis of 1HPN structure. A key reason for the stability of multiple low energy conformations was the contribution of intermediate water bridges, which is usually not evaluated in most MD studies of H/HS.
Analysis of movement recursions to detect reproductive events and estimate their fate in central place foragers
Authors: Picardi Simona , Smith Brian J. , Boone Matthew E. , Frederick Peter C. , Cecere Jacopo G. , Rubolini Diego , Serra Lorenzo , Pirrello Simone , Borkhataria Rena R. , Basille Mathieu 
Published: February 2019

AbstractRecursive movement patterns have been used to detect behavioral structure within individual movement trajectories in the context of foraging ecology, home-ranging behavior, and predator avoidance. Some animals exhibit movement recursions to locations that are tied to reproductive functions, including nests and dens; while existing literature recognizes that, no method is currently available to explicitly target different types of revisited locations. Moreover, the temporal persistence of recursive movements to a breeding location can carry information regarding the fate of breeding attempts, but it has never been used as a metric to quantify recursive movement patterns. Here, we introduce a method to locate breeding attempts and estimate their fate from GPS-tracking data of central place foragers. We tested the performance of our method in three bird species differing in breeding ecology (wood stork (Mycteria americana), lesser kestrel (Falco naumanni), Mediterranean gull (Ichthyaetus melanocephalus)) and implemented it in the R package ‘nestR’. We identified breeding sites based on the analysis of recursive movements within individual tracks. Using trajectories with known breeding attempts, we estimated a set of species-specific criteria for the identification of nest sites, which we further validated using non-reproductive individuals as controls. We then estimated individual nest survival as a binary measure of reproductive fate (success, corresponding to fledging of at least one chick, or failure) from nest-site revisitation histories during breeding attempts, using a Bayesian hierarchical modeling approach that accounted for temporally variable revisitation patterns, probability of visit detection, and missing data. Across the three species, positive predictive value of the nest-site detection algorithm varied between 87-100% and sensitivity between 88-92%, and we correctly estimated the fate of 86-100% breeding attempts. By providing a method to formally distinguish among revisited locations that serve different ecological functions and introducing a probabilistic framework to quantify temporal persistence of movement recursions, we demonstrated how the analysis of recursive movement patterns can be applied to estimate reproduction in central place foragers. Beyond avian species, the principles of our method can be applied to other central place foraging breeders such as denning mammals. Our method estimates a component of individual fitness from movement data and will help bridge the gap between movement behavior, environmental factors, and their fitness consequences.
CD29 marks superior cytotoxic human T cells
Authors: Nicolet Benoît P. , Guislain Aurélie , van Alphen Floris P.J. , Gomez-Eerland Raquel , Schumacher Ton N. M. , den Biggelaar Maartje van , Wolkers Monika C. 
Published: February 2019

ABSTRACTCytotoxic CD8+T cells can effectively kill target cells by producing cytokines, chemokines and granzymes. Expression of these effector molecules is however highly divergent, and tools that identify and pre-select potent killer cells are lacking. Human CD8+T cells can be divided into IFN-γ and IL-2 producing cells. Unbiased RNA-sequencing and proteomics analysis on cytokine-producing fixed cells revealed that IL-2+T cells produce helper cytokines, and that IFN-γ+T cells produce cytotoxic molecules. IFN-γ+T cells could be identified with the surface marker CD29 already prior to stimulation. CD29 also marked T cells with cytotoxic gene expression from different tissues in single-cell RNA-sequencing data. Notably, the cytotoxic features of CD29+T cells were maintained during cell culture, suggesting a stable phenotype. Pre-selecting CD29-expressing MART1 TCR-engineered T cells potentiated the killing of target cells. We therefore propose that selecting for CD29+T cells could boost the anti-tumoral activity of T cell therapeutics.
Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib Penetration into Liver Metastases of Gastrointestinal Stromal Tumors
Authors: Sammour Denis Abu , Marsching Christian , Geisel Alexander , Erich Katrin , Schulz Sandra , Guevara Carina Ramallo , Rabe Jan-Hinrich , Marx Alexander , Findeisen Peter , Hohenberger Peter , Hopf Carsten 
Published: February 2019

AbstractMass spectrometry imaging (MSI) is an enabling technology for label-free drug disposition studies at high spatial resolution in life science- and pharmaceutical research. We present the first extensive clinical matrix-assisted laser desorption/ionization (MALDI) quantitative mass spectrometry imaging (qMSI) study of drug uptake and distribution in clinical specimen, analyzing 56 specimens of tumor and corresponding non-tumor tissues from 28 imatinib-treated patients with biopsy-proven gastrointestinal stromal tumors (GIST). For validation, we compared MALDI-TOF-qMSI with conventional UPLC-ESI-QTOF-MS-based quantification from tissue extracts and with ultra-high resolution MALDI-FTICR-qMSI. We introduced a novel generalized nonlinear calibration model of drug quantities based on focused computational evaluation of drug-containing areas that enabled better data fitting and assessment of the inherent method nonlinearities. Imatinib tissue spatial maps revealed striking inefficiency in drug penetration into GIST liver metastases even though the corresponding healthy liver tissues in the vicinity showed abundant imatinib levels beyond the limit of quantification (LOQ), thus providing evidence for secondary drug resistance independent of mutation status. Taken together, these findings underline the important application of MALDI-qMSI for studying the spatial distribution of molecularly targeted therapeutics in oncology.
Perceptual saccadic suppression starts in the retina
Authors: Idrees Saad , Baumann Matthias P. , Franke Felix , Münch Thomas A. , Hafed Ziad M. 
Published: February 2019

AbstractVisual sensitivity, probed through perceptual detectability of very brief visual stimuli, is strongly impaired around the time of rapid eye movements. This robust perceptual phenomenon, called saccadic suppression, is frequently attributed to active suppressive signals that are directly derived from eye movement commands. Here we show instead that visual-only mechanisms, activated by saccade-induced image shifts, can account for all perceptual properties of saccadic suppression that we have investigated. Such mechanisms start at, but are not necessarily exclusive to, the very first stage of visual processing in the brain, the retina. Critically, neural suppression originating in the retina outlasts perceptual suppression around the time of saccades, suggesting that extra-retinal movement-related signals, rather than causing suppression, may instead act to shorten it. Our results demonstrate a far-reaching contribution of visual processing mechanisms to perceptual saccadic suppression, starting in the retina, without the need to invoke explicit motor-based suppression commands.
SNAP23 is required for the maintenance of meiotic arrest and cortical granule exocytosis in mouse oocytes
Authors: Mehlmann Lisa M. , Uliasz Tracy F. , Lowther Katie M. 
Published: February 2019

ABSTRACTMammalian oocytes are stored in the ovary for prolonged periods, arrested in meiotic prophase. During this period, their plasma membranes are constantly being recycled by endocytosis and exocytosis. However, the function of this membrane turnover is unknown. Here, we investigated the requirement for exocytosis in the maintenance of meiotic arrest. Using a newly developed method for rapidly and specifically depleting proteins in oocytes, we have identified the SNARE protein, SNAP23, to be required for meiotic arrest. Degradation of SNAP23 causes premature meiotic resumption in follicle-enclosed oocytes. The reduction in SNAP23 is associated with loss of gap junction communication between the oocyte and surrounding follicle cells. Reduction of SNAP23 protein also inhibits cortical granule exocytosis in response to a Ca2+ stimulus, as measured by lectin staining and cleavage of ZP2. Our results show an essential role for SNAP23 in two key processes that occur in mouse oocytes and eggs.SummaryThe SNARE protein, SNAP23, is required to maintain gap junction communication between the oocyte and follicle cells that is needed to maintain oocyte meiotic arrest, as well as for cortical granule exocytosis at fertilization.
Self-reported Health is Related to Body Height and Waist Circumference in Rural Indigenous and Urbanised Latin-American Populations
Authors: Leongoméz Juan David , Sánchez Oscar R. , Vásquez-Amézquita Milena , Valderrama Eugenio , Castellanos-Chacón Andrés , Morales-Sánchez Lina , Nieto Javier , González-Santoyo Isaac 
Published: February 2019

AbstractBody height is a life-history component. It involves important costs for its expression and maintenance, which may originate trade-offs on other costly components such as reproduction or immunity. Although previous evidence has supported the idea that human height could be a sexually selected trait, the explanatory mechanisms that underlie this selection are poorly understood. Despite extensive studies on the association between height and attractiveness, the role of immunity in linking this relation is scarcely studied, particularly in non-Western populations. Here, we tested whether human height is related to health measured by self-perception, and relevant nutritional and health anthropometric indicators in three Latin-American populations that widely differ in socioeconomic and ecological conditions: two urbanised populations from Bogota (Colombia) and Mexico City (Mexico), and one isolated indigenous population (Me’Phaa, Mexico). Results showed that self-reported health is best predicted by an interaction between height and waist circumference, and the costs associated with large waist circumference are height-dependent, affecting taller people more than shorter individuals. If health and genetic quality cues play an important role in human mate-choice, and height and waist interact to signal health, its evolutionary consequences, including cognitive and behavioural effects, should be addressed in future research.