bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic, Physiologic, and Behavioral Predictors of Cardiorespiratory Fitness in Specialized Military Men
Authors: Taylor Marcus K , Hernández Lisa M , Schoenherr Matthew R , Stump Jeremiah 
Published: March 2019

AbstractIntroductionCardiorespiratory fitness (CRF) is a crucial performance requirement of specialized military occupations. Age and physical activity are established predictors of CRF, but it is not clear how these predictors combine with each other and/or with genetic predisposition. The goal of this study was to derive inclusive explanatory models of CRF in US Navy Explosive Ordnance Disposal (EOD) operators, synthesizing conventional (e.g., age, body composition, and physical activity) and novel influences (e.g., genetic variance).Materials and MethodsIn this cross-sectional study, 40 male, active duty EOD operators completed a graded exercise test to assess maximal oxygen consumption and ventilatory threshold (VT) using the Bruce protocol. Aerobic performance was further quantified via time of test termination and time at which VT was achieved. Body composition was determined via dual x-ray absorptiometry, and physical activity was assessed by self-report. Genetic variants underlying human stress systems (5HTTLPR, BclI, −2 C/G, and COMT) were assayed. Descriptive analyses were conducted to summarize subject characteristics. Hypotheses were tested with linear regression models. Specifically, separate univariate regression models first determined associations between each of the independent and dependent variables. This protocol was approved by the Naval Health Research Center Institutional Review Board (NHRC.2015.0013).ResultsIn univariate regression models, age, body composition, physical activity, and 5HTTLPR consistently predicted CRF and/or aerobic performance (R2 range 0.07–0.55). Multivariate regression models routinely outperformed the univariate models, explaining 36–62% of variance.ConclusionThis study signifies a shift toward inclusive explanatory models of CRF and aerobic performance, accounting for combined roles of genetic, physiologic, and behavioral influences. Although we were able to quantify combined effects, we were unable to evaluate interaction effects (e.g., gene–gene, gene–behavior) due to limited statistical power. Other limitations are that this specialized military population may not readily generalize to broader populations, and the current sample was all male. Considering these limitations, we aim to replicate this study in various populations, both male and female. Despite its limitations, this study reflects a shift toward more comprehensive predictive models of CRF, explaining the unique and shared contributions of genetic predisposition, physiology, and behavior. These findings have implications for assessment, selection, and training of specialized military members, and may also impact mission success and survivability. Future studies are needed to better characterize additive, interactive, and mediated effects.
Effects of Early Altitude Exposure on the Open Abdomen After Laparotomy in Trauma
Authors: Martin Grace E , Johnson Mark , Veile Rose , Friend Lou Ann , Elterman Joel B , Johannigman Jay A , Pritts Timothy A , Goodman Michael D , Makley Amy T 
Published: March 2019

AbstractIntroductionWhile damage control surgery and resuscitation techniques have revolutionized the care of injured service members who sustain severe traumatic hemorrhage, the physiologic and inflammatory consequences of hemostatic resuscitation and staged abdominal surgery in the face of early aeromedical evacuation (AE) have not been investigated. We hypothesized that post-injury AE with an open abdomen would have significant physiologic and inflammatory consequences compared to AE with a closed abdomen.Materials and MethodsEvaluation of resuscitation and staged abdominal closure was performed using a murine model of hemorrhagic shock with laparotomy. Mice underwent controlled hemorrhage to a systolic blood pressure of 25 mmHg and received either no resuscitation, blood product resuscitation, or Hextend resuscitation to a systolic blood pressure of either 50 mmHg (partial resuscitation) or 80 mmHg (complete resuscitation). Laparotomies were either closed prior to AE (closed abdomens) or left open during AE (open abdomens) and subsequently closed. AE was simulated with a 1-hour exposure to a hypobaric hypoxic environment at 8,000 feet altitude. Mice were euthanized at 0, 4, or 24 hours following AE. Serum was collected and analyzed for physiologic variables and inflammatory cytokine levels. Samples of lung and small intestine were collected for tissue cytokine and myeloperoxidase analysis as indicators of intestinal inflammation. Survival curves were also performed.ResultsUnresuscitated mice sustained an 85% mortality rate from hemorrhage and laparotomy, limiting the assessment of the effect of simulated AE in these subgroups. Overall survival was similar among all resuscitated groups regardless of the presence of hypobaric hypoxia, type of resuscitation, or abdominal closure status. Simulated AE had no observed effects on acid/base imbalance or the inflammatory response as compared to ground level controls. All mice experienced both metabolic acidosis and an acute inflammatory response after hemorrhage and injury, represented by an initial increase in serum interleukin (IL)-6 levels. Furthermore, mice with open abdomens had an elevated inflammatory response with increased levels of serum IL-10, serum tumor necrosis factor alpha, intestinal IL-6, intestinal IL-10, and pulmonary myeloperoxidase.ConclusionThese results demonstrate the complex interaction of AE and temporary or definitive abdominal closure after post-injury laparotomy. Contrary to our hypothesis, we found that AE in those animals with open abdomens is relatively safe with no difference in mortality compared to those with closed abdomens. However, given the physiologic and inflammatory changes observed in animals with open abdomens, further evaluation is necessary prior to definitive recommendations regarding the safety or downstream effects of exposure to AE prior to definitive abdominal closure.
Quantitative multiplexed ChIP reveals global alterations that shape promoter bivalency in ground state embryonic stem cells
Authors: Kumar Banushree , Elsässer Simon J 
Published: March 2019

ABSTRACTTo understand the epigenetic foundation of naïve pluripotent cells, we implement a quantitative multiplexed ChIP-Seq method (MINUTE-ChIP) comparing mouse ESC grown in 2i versus Serum conditions. Combined with quantitative western blot and mass spectrometry, we find compelling evidence for a broad H3K27me3 hypermethylation of the genome, concomitant with the widespread loss of DNA CpG methylation. We show that opposing action of EZH2 and JMJD3/UTX shape the H3K27me3 landscape, with almost all bivalent promoters stably retaining high H3K27me3 levels in 2i. In parallel, we show a mechanistically uncoupled, global decrease of H3K4me3 and strong reduction at bivalent promoters, suggesting that low H3K4me3 and high H3K27me3 levels at bivalent promoters safeguard naïve pluripotency.
Metabolic Cost of Rapid Adaptation of Single Yeast Cells
Authors: Woronoff Gabrielle , Nghe Philippe , Baudry Jean , Boitard Laurent , Braun Erez , Griffiths Andrew D. , Bibette Jérôme 
Published: March 2019

AbstractCells can rapidly adapt to changing environments through non-genetic processes; however, the metabolic cost of such adaptation has never been considered. Here we demonstrate metabolic coupling in a remarkable, rapid adaptation process (10-3cells/hour) by simultaneously measuring metabolism and division of thousands of individual Saccharomyces cerevisiae cells using a droplet microfluidic system. Following a severe challenge, most cells, while not dividing, continue to metabolize, displaying a remarkably wide diversity of metabolic trajectories from which adaptation events can be anticipated. Adaptation requires the consumption of a characteristic amount of energy, indicating that it is an active process. The demonstration that metabolic trajectories predict a priori adaptation events provides the first evidence of tight energetic coupling between metabolism and regulatory reorganization in adaptation.One Sentence SummaryDemonstration of the tight coupling between metabolic activity and regulatory processes during rapid adaptation at the single-cell level.
Genomic architecture of phenotypic plasticity of complex traits in tetraploid wheat in response to water stress
Authors: Fatiukha Andrii , Deblieck Mathieu , Klymiuk Valentina , Merchuk-Ovnat Lianne , Peleg Zvi , Ordon Frank , Fahima Tzion , Korol Abraham B. , Saranga Yehoshua , Krugman Tamar 
Published: March 2019

AbstractPhenotypic plasticity is one of the main mechanisms of adaptation to abiotic stresses via changes in critical developmental stages. Altering flowering phenology is a key evolutionary strategy of plant adaptation to abiotic stresses in order to achieve maximum possible reproduction. The current study is the first to apply the linear regression residuals as a drought plasticity scores, while taking into account the differences in flowering phenology and trait variation under non-stress conditions. We characterized the genomic architecture of 17 complex traits and their drought plasticity using a mapping population derived from a cross between durum wheat (Triticum durum) and wild emmer wheat (T. dicoccoides). We identified 79 QTLs, of which 33 were plastic in response to water stress and exhibited epistatic interactions and/or pleiotropy between the initial and plasticity traits.Vrn-B3 (TaTF1)residing within an interval of a major drought-escape QTL was proposed as a candidate gene. The favorable alleles for most of the plasticity QTLs were contributed by wild emmer, demonstrating the high potential of wild relatives for wheat improvement. Our study presents a new approach for quantification of plant adaptation to various stresses and provides new insights into the genetic basis of wheat complex traits under water-deficit stress.HighlightThe study presents a new approach for quantification of plant adaptation to various stresses and provides new insights into the genetic basis of wheat complex traits under water-deficit stress.
Postural Representations of the Hand in Primate Sensorimotor Cortex
Authors: Goodman James M. , Tabot Gregg A. , Lee Alex S. , Suresh Aneesha K. , Rajan Alexander T. , Hatsopoulos Nicholas G. , Bensmaia Sliman J. 
Published: March 2019

SummaryDexterous hand control requires not only a sophisticated motor system but also a sensory system to provide tactile and proprioceptive feedback. To date, the study of the neural basis of proprioception in cortex has focused primarily on reaching movements, at the expense of hand-specific behaviors such as grasp. To fill this gap, we record both the time-varying hand kinematics and the neural activity evoked in somatosensory and motor cortices as monkeys grasp a variety of different objects. We find that neurons in somatosensory cortex, as well as in motor cortex, preferentially track postures of multi-joint combinations spanning the entire hand. This contrasts with neural responses during reaching movements, which preferentially track movement kinematics of the arm rather than its postural configuration. These results suggest different representations of arm and hand movements likely adapted to suit the different functional roles of these two effectors.
HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation
Authors: van Dierendonck Xanthe A.M.H. , de la Rosa Rodriguez Montserrat A. , Georgiadi Anastasia , Mattijssen Frits , Dijk Wieneke , van Weeghel Michel , Singh Rajat , Borst Jan Willem , Stienstra Rinke , Kersten Sander 
Published: March 2019

ABSTRACTObesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.
The neurofunctional basis of affective startle modulation in humans – evidence from combined facial EMG-fMRI
Authors: Kuhn Manuel , Wendt Julia , Sjouwerman Rachel , Büchel Christian , Hamm Alfons , Lonsdorf Tina B. 
Published: March 2019

AbstractThe startle reflex, a protective response elicited by an immediate, unexpected sensory event, ispotentiatedwhen evoked during threat andinhibitedduring safety. In contrast to skin conductance responses or pupil dilation, modulation of the startle reflex is valence-specific and consideredthecross-species translational tool for defensive responding.Rodent models implicate a modulatory pathway centering on the brainstem (i.e., nucleus reticularis pontis caudalis, PnC) and the centromedial amygdala (CeM) as key hubs for flexibly integrating valence information into differential startle magnitude.We employed innovative combined EMG-fMRI measurements in two independent experiments and samples and provide converging evidence for the involvement of these key regions in the modulatory acoustic startle reflex pathway in humans. Furthermore, we provide the crucial direct link between EMG startle eye-blink magnitude and neural response strength.We argue that startle-evoked amygdala responding and its affective modulation may hold promise as an important novel tool for affective neuroscience.
Translational products encoded by novel ORFs may form protein-like structures and have biological functions
Authors: Erady Chaitanya , Chong David , Meena Narendra , Puntambekar Shraddha , Chauhan Ruchi , Umrania Yagnesh , Andreani Adam , Nel Jean , Wayland Matthew T. , Pina Cristina , Lilley Kathryn S. , Prabakaran Sudhakaran 
Published: March 2019

AbstractTranslation products encoded by non canonical or novel open reading frame (ORF) genomic regions are generally considered too small to play any significant biological role, and dismissed as inconsequential. In this study, we show that mutations mapping to novel ORFs have significantly higher pathogenicity scores than mutations in protein-coding regions. Importantly, novel ORFs can translate into protein-like structures with putative independent biological functions that can be of relevance in disease states, including cancer. We thus provide strong evidence to support the systematic study of novel ORFs to gain new insights into normal biological and disease processes.One Sentence SummaryNon coding regions may encode protein-like products that are important to understand diseases.
Dynamic neuronal activation of a distributed cortico-basal ganglia-thalamus loop in learning a delayed sensorimotor task
Authors: Gu Xiaowei , Li Chengyu T. 
Published: March 2019

AbstractThe cortico-basal ganglia-thalamus (CBT) loop is important for behavior. However, the activity and learning-related modulation within the loop in behavior remain unclear. To tackle this problem, we trained mice to perform a delayed sensorimotor-transformation task and recorded single-unit activity during learning simultaneously from four regions in a CBT loop: prelimbic area (PrL), posterior premotor cortex (pM2), dorsomedial caudate/putamen (dmCP), and mediodorsal thalamus (MD). Sensory and decision related information were encoded by the neurons within the loop, with weak interaction among neurons of different coding ability. The functional interaction among regions within the loop was dynamically routed in the loop during different behavioral phases and contributed to explain decision-related neuronal activity. The neurons of PrL and dmCP exhibited learning-related reorganization in neuronal activity and more persistent coding of sensory and decision-related information. Thus, both sensory- and decision-related information are processed in a functionally interacted CBT loop that is modulated by learning.
Mechanics of wood boring by beetle mandibles
Authors: Kundanati Lakshminath , Chahare Nimesh R. , Jaddivada Siddhartha , Karkisaval Abhijith G. , Pugno Nicola M. , Gundiah Namrata 
Published: March 2019

AbstractWood boring is a feature of several insect species and is a major cause of severe and irreparable damage to trees. Adult females typically deposit their eggs on the stem surface under bark scales. The emerging hatchlings live within hard wood during their larval phase, avoiding possible predation, whilst continually boring and tunneling through wood until pupation. A study of wood boring by insects offers unique insights into the bioengineering principles that drive evolutionary adaptations. We show that larval mandibles of the coffee wood stem borer beetle (Xylotrechus quadripes: Cerambycidae) have a highly sharp cusp edge to initiate fractures inArabicawood and a suitable shape to generate small wood chips that are suitable for digestion. Cuticle hardness at the tip is significantly enhanced through zinc-enrichment. Finite element model of the mandible, based on the differential material properties at the tip, intermediate and base regions of the mandible, showed highest stresses in the tip region; these decreased to significantly lower values at the start of the hollow section. A hollow architecture significantly reduces bending stresses at mandibular base without compromising the structural integrity. A scaling model based on a fracture mechanics framework shows the importance of the mandible shape in generating optimal chip sizes. These findings contain general principles in tool design and put in focus interactions of insects and their woody hosts.
Human liver organoids; a patient-derived primary model for HBV Infection and Related Hepatocellular Carcinoma
Authors: Crignis Elisa De , Romal Shahla , Carofiglio Fabrizia , Moulos Panagiotis , Verstegen Monique M.A. , Khalid Mir Mubashir , Pourfarzad Farzin , Rao Shringar , Bazrafshan Ameneh , Koutsothanassis Christina , Gehart Helmuth , Kan Tsung Wai , Palstra Robert-Jan , Boucher Charles , IJzermans Jan M.N. , Huch Meritxell , Boj Sylvia F. , Vries Robert , Clevers Hans , van der Laan Luc , Hatzis Pantelis , Mahmoudi Tokameh 
Published: March 2019

AbstractThe molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV infected organoids produced cccDNA, expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity as well as for drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor NTCP by lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the HCC cohort on the TCGA LIHC dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for disease surveillance and development of HCC in HBV infected patients.
Single-Organelle Quantification Reveals Stoichiometric and Structural Variability of Carboxysomes Dependent on the Environment
Authors: Sun Yaqi , Wollman Adam J. M. , Huang Fang , Leake Mark C. , Liu Lu-Ning 
Published: March 2019

ABSTRACTThe carboxysome is a complex, proteinaceous organelle that plays essential roles in carbon assimilation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble in space to form an icosahedral structure. Despite its significance in enhancing CO2fixation and potentials in bioengineering applications, the formation of carboxysomes and their structural composition, stoichiometry and adaptation to cope with environmental changes remain unclear. Here we use live-cell single-molecule fluorescence microscopy, coupled with confocal and electron microscopy, to decipher the absolute protein stoichiometry and organizational variability of single β-carboxysomes in the model cyanobacteriumSynechococcus elongatusPCC7942. We determine the physiological abundance of individual building blocks within the icosahedral carboxysome. We further find that the protein stoichiometry, diameter, localization and mobility patterns of carboxysomes in cells depend sensitively on the microenvironmental levels of CO2and light intensity during cell growth, revealing cellular strategies of dynamic regulation. These findings, also applicable to other bacterial microcompartments and macromolecular self-assembling systems, advance our knowledge of the principles that mediate carboxysome formation and structural modulation. It will empower rational design and construction of entire functional metabolic factories in heterologous organisms, for example crop plants, to boost photosynthesis and agricultural productivity.One Sentence SummaryDetermination of absolute protein stoichiometry reveals the organizational variability of carboxysomes in response to microenvironmental changesThe authors responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Author (www.plantcell.org) is: Lu-Ning Liu (luning.liu@liverpool.ac.uk).