bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic inequalities in co-morbidity of overweight, obesity and mental ill-health from adolescence to mid-adulthood in two national birth cohort studies
Authors: Khanolkar Amal R. , Patalay Praveetha 
Published: October 2020

AbstractAimTo examine socioeconomic inequalities in risk of comorbidity between overweight (including obesity) and mental ill-health in two national cohorts. We investigated independent effects of childhood and adulthood socioeconomic disadvantage on comorbidity from childhood to mid-adulthood, and differences by sex and cohort.MethodsData were from 1958 National Child Development Study (NCDS58) and 1970 British Cohort Study (BCS70) [total N=30,868, 51% males] assessed at ages 10, 16, 23, 34 and 42 years. Socioeconomic indicators included childhood and adulthood social class and educational level. Risk for i. having healthy BMI and mental ill-health, ii. overweight and good mental health, and iii. overweight and mental ill-health was analysed using multinomial logistic regression.ResultsSocioeconomic disadvantage was consistently associated with greater risk for overweight-mental ill-health comorbidity at all ages (RRR 1.43, 2.04, 2.38, 1.64 and 1.71 at ages 10, 16, 23, 34 and 42 respectively for unskilled/skilled vs. professional/managerial class). The observed inequalities in co-morbidity were greater than that observed for either condition alone (overweight; RRR 1.39 and 1.25, mental ill-health; 1.36 and 1.22 at ages 16 and 42 respectively, for unskilled/skilled vs. professional/managerial class). In adulthood, childhood and adulthood socioeconomic disadvantage were independently associated with comorbid overweight-mental ill-health, with a clear inverse gradient between educational level and risk for comorbidity; no education, RRR 6.11 (95% CI 4.31-8.65) at age 34 and 4.42 (3.28-5.96) at age 42 compared to university education. There were no differences observed in the extent of inequalities by sex and differences between cohorts were limited.ConclusionsSocioeconomic disadvantage in childhood and adulthood are consistently and independently associated with greater risk for mental ill-health and overweight separately, and even greater inequalities in the risk for comorbidity between both conditions through the lifecourse. These findings are significant given the increasing global prevalence of obesity and mental ill-health, and their implications for lifelong health and mortality.
Spatially expandable fiber-based probes as a multifunctional deep brain interface
Authors: Jiang Shan , Patel Dipan C. , Kim Jongwoon , Yang Shuo , Mills William A. , Zhang Yujing , Wang Kaiwen , Feng Ziang , Vijayan Sujith , Cai Wenjun , Wang Anbo , Guo Yuanyuan , Kimbrough Ian F. , Sontheimer Harald , Jia Xiaoting 
Published: October 2020

AbstractUnderstanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, usingThy1-ChR2-YFPmice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.
Activating mGlu3metabotropic glutamate receptors rescues schizophrenia-like cognitive deficits through metaplastic adaptations within the hippocampus
Authors: Dogra Shalini , Stansley Branden J. , Xiang Zixiu , Qian Weilun , Gogliotti Rocco G. , Nicoletti Ferdinando , Lindsley Craig W. , Niswender Colleen M. , Joffe Max E. , Conn P. Jeffrey 
Published: October 2020

AbstractBackgroundPolymorphisms inGRM3, the gene encoding the mGlu3 metabotropic glutamate receptor, are associated with impaired cognition and neuropsychiatric disorders such as schizophrenia. Limited availability of selective genetic and molecular tools has hindered progress in developing a clear understanding of the mechanisms through which mGlu3 receptors regulate synaptic plasticity and cognition.MethodsWe examined associative learning in mice with trace fear conditioning, a hippocampal-dependent learning task disrupted in patients with schizophrenia. Underlying cellular mechanisms were assessed usingex vivohippocampal slice preparations with selective pharmacological tools and selective genetic deletion of mGlu3 receptor expression in specific neuronal subpopulations.ResultsmGlu3receptor activation enhanced trace fear conditioning and reversed deficits induced by subchronic phencyclidine. Mechanistic studies revealed that mGlu3receptor activation induced metaplastic changes, biasing afferent stimulation to induce long-term potentiation through a mGlu5receptor-dependent, endocannabinoid-mediated, disinhibitory mechanism. Selective genetic deletion of either mGlu3or mGlu5from hippocampal pyramidal cells eliminated effects of mGlu3activation, revealing a novel mechanism by which mGlu3and mGlu5interact to enhance cognitive function.ConclusionsThese data demonstrate that activation of mGlu3receptors in hippocampal pyramidal cells enhances hippocampal-dependent cognition in control and impaired mice by inducing a novel form of metaplasticity to regulate circuit function – providing a clear mechanism through which genetic variation inGRM3can contribute to cognitive deficits. Developing approaches to positively modulate mGlu3receptor function represents an encouraging new avenue for treating cognitive disruption in schizophrenia and other psychiatric diseases.
Electroencephalogram Monitoring of Depth of Anesthesia during Office-Based Anesthesia
Authors: Nagaraj Sunil B. , Kahali Pegah , Purdon Patrick L. , Shapiro Fred E. , Westover M. Brandon 
Published: October 2020

ABSTRACTObjectiveElectroencephalogram (EEG) monitors are often used to monitor depth of general anesthesia. EEG monitoring is less well developed for lighter levels of anesthesia. Here we present an automated method to monitor the depth of anesthesia for office based procedures using EEG spectral features.MethodsWe analyze EEG recordings from 30 patients undergoing sedation using a multimodal anesthesia strategy. Level of sedation during the procedure is coded using the Richmond Agitation and Sedation Scale (RASS). The power spectrum from the frontal EEG is used to infer the level of sedation, by training a logistic regression model with elastic net regularization. Area under the receiver operator characteristic curve (AUC) is used to evaluate how well the automated system distinguishes awake from sedated EEG epochs.ResultsEEG power spectral characteristics vary systematically and consistently across patients with the levels of light anesthesia and relatively healthy patients encountered during office-based anesthesia procedures. The logistic regression model using spectral EEG features distinguishes awake and sedated states with an AUC of 0.85 (± 0.14).ConclusionsOur results demonstrate that frontal EEG spectral features can reliably monitor sedation levels during office based anesthesia.
TaqMan Array Cards enable monitoring of diverse enteric pathogens across environmental and host reservoirs
Authors: Lappan Rachael , Henry Rebekah , Chown Steven L. , Luby Stephen P. , Higginson Ellen E. , Bata Lamiya , Jirapanjawat Thanavit , Schang Christelle , Openshaw John J. , O’Toole Joanne , Lin Audrie , Tela Autiko , Turagabeci Amelia , Wong Tony H.F. , French Matthew A. , Brown Rebekah R. , Leder Karin , Greening Chris , McCarthy David 
Published: October 2020

AbstractBackgroundMultiple bacteria, viruses, protists, and helminths cause enteric infections that greatly impact human health and wellbeing. These enteropathogens are transmitted via several pathways through human, animal, and environmental reservoirs. Individual quantitative PCR (qPCR) assays have been extensively used to detect enteropathogens within these types of samples, whereas the TaqMan Array Card (TAC) that allows simultaneous detection of multiple enteropathogens has only previously been validated in human clinical samples.MethodsHere, we performed a comprehensive double-blinded comparison of the performance of a custom TAC relative to standard qPCR for the detection of eight enteric targets, by using spiked samples, wastewater from Melbourne (Australia), and human, animal, and environmental samples from informal settlements in Suva, Fiji.FindingsBoth methods exhibited high and comparable specificity (TAC: 100%, qPCR: 94%), sensitivity (TAC: 92%; qPCR: 100%), and quantitation accuracy (TAC: 91%; qPCR: 99%) in non-inhibited sample matrices. PCR inhibitors substantially impacted detection via TAC, though this issue was alleviated by 10-fold sample dilution. Among samples from informal settlements, the two techniques were comparable for detection (89% agreement) and quantitation (R2= 0.82). The TAC additionally included 38 other targets, enabling detection of diverse faecal pathogens and extensive environmental contamination that would be prohibitively labour intensive to assay by standard qPCR.InterpretationOverall, the two techniques produce comparable results across diverse sample types, with qPCR prioritising greater sensitivity and quantitation accuracy, and TAC trading small reductions in these for a cost-effective larger enteropathogen panel that enables a greater number of enteric pathogens to be analysed concurrently, which is beneficial given the abundance and variety of enteric pathogens in environments such as urban informal settlements. The ability to monitor multiple enteric pathogens across diverse reservoirs in turn allows better resolution of pathogen exposure pathways, and the design and monitoring of interventions to reduce pathogen load.FundingWellcome TrustOur Planet, Our Healthprogram [OPOH grant 205222/Z/16/Z].
Exact and WKB-approximate distributions in a gene expression model with feedback in burst frequency, burst size, and protein stability
Authors: Bokes Pavol 
Published: October 2020

AbstractThe expression of individual genes into functional protein molecules is a noisy dynamical process. Here we model the protein concentration as a jump–drift process which combines discrete stochastic production bursts (jumps) with continuous deterministic decay (drift). We allow the drift rate, the jump rate, and the jump size to depend on the protein level to implement feedback in protein stability, burst frequency, and burst size. We specifically focus on positive feedback in burst size, while allowing for arbitrary autoregulation in burst frequency and protein stability. Two versions of feedback in burst size are thereby considered: in the first, newly produced molecules instantly participate in feedback, even within the same burst; in the second, within-burst regulation does not occur due to the so-called infinitesimal delay. Without infinitesimal delay, the model is explicitly solvable; with its inclusion, an exact distribution to the model is unavailable, but we are able to construct a WKB approximation that applies in the asymptotic regime of small but frequent bursts. Comparing the asymptotic behaviour of the two model versions, we report that they yield the same WKB quasi-potential but a different exponential prefactor. We illustrate the difference on the case of a bimodal protein distribution sustained by a sigmoid feedback in burst size: we show that the omission of the infinitesimal delay overestimates the weight of the upper mode of the protein distribution. The analytic results are supported by kinetic Monte-Carlo simulations.
Cambium-specific Transcriptome Analysis of Paulownia to Study the Molecular Impacts of Winter and Spring Seasons on Tree Growth
Authors: Perry Zachary D , Saminathan Thangasamy , Arun Alok , Vaidya Brajesh N , Basu Chhandak , Reddy Umesh K , Joshee Nirmal 
Published: October 2020

AbstractPaulownia (Paulownia elongata) is a fast-growing, multipurpose deciduous hardwood species that grows in a wide range of temperatures from –30 °C to 45 °C. Seasonal cues influence the secondary growth of tree stems, including cambial activity, wood chemistry, and transition to latewood formation. In this study, ade novotranscriptome approach was conducted to identify the transcripts expressed in vascular cambial tissue from senescent winter and actively growing spring seasons. Illumina paired-end sequenced cambial transcriptome generated 297,049,842 clean reads which finally yielded 61,639 annotated unigenes. Based on non- redundant protein database analyses, Paulownia cambial unigenes shared highest homology (64.8%) withErythranthe guttata. A total of 35,471 unigenes resulted from KEGG annotation that were mapped to 128 pathways with metabolic pathways dominated among all. Additionally, DEG analysis showed that 2,688 and 7,411 genes were significantly upregulated and downregulated, respectively in spring compared to winter. Interestingly, quite a number of transcripts belonging to heat shock proteins were upregulated in spring season. RT-qPCR expression results of fifteen wood-forming candidate genes involved in hemicellulose, cellulose, lignin, auxin and cytokinin pathways showed that the hemicellulose genes (CSLC4, FUT1, AXY4, GATL1, andIRX19) were significantly upregulated in spring season tissues when compared to winter tissues. In contrast, lignin pathway genesCCR1andCAD1were upregulated in winter cambium. Finally, a transcriptome-wide marker analysis identified 11,338 Simple Sequence Repeat (SSRs). The AG/CT dinucleotide repeat predominately represented all SSRs. Altogether, the cambial transcriptomic analysis reported here highlights the molecular events of wood formation during winter and spring. The identification of candidate genes involved in the cambial growth provides a roadmap of wood formation in Paulownia and other trees for the seasonal growth variation.
Selective and Improved Photoannealing of Microporous Annealed Particle (MAP) Scaffolds
Authors: Pfaff Blaise N. , Pruett Lauren J. , Cornell Nicholas J. , de Rutte Joseph , Di Carlo Dino , Highley Christopher B. , Griffin Donald R. 
Published: October 2020

AbstractMicroporous Annealed Particle (MAP) scaffolds consist of a slurry of hydrogel microspheres that undergo annealing to form a solid scaffold. MAP scaffolds have contained functional groups with dual abilities to participate in Michael-type addition (gelation) and radical polymerization (photoannealing). Functional groups with efficient Michael-type additions react with thiols and amines under physiological conditions, limiting usage for therapeutic delivery. We present a heterofunctional maleimide/methacrylamide 4-arm PEG macromer (MethMal) engineered for selective photopolymerization compatible with multiple polymer backbones. Rheology using two classes of photoinitiators demonstrates advantageous photopolymerization capabilities. Functional assays show benefits for therapeutic delivery and 3D printing without impacting cell viability.
Bacterial microcompartments linked to the flavin-based extracellular electron transfer drives anaerobic ethanolamine utilization inListeria monocytogenes
Authors: Zeng Zhe , Boeren Sjef , Bhandula Varaang , Light Samuel H. , Smid Eddy J. , Notebaart Richard A. , Abee Tjakko 
Published: October 2020

AbstractEthanolamine (EA) is a valuable microbial carbon and nitrogen source derived from phospholipids present in cell membranes. EA catabolism is suggested to occur in so-called bacterial microcompartments (BMCs) and activation of EA utilization (eut) genes is linked to bacterial pathogenesis. Despite reports showing that activation ofeutinListeria monocytogenesis regulated by a vitamin B12-binding riboswitch and that upregulation ofeutgenes occurs in mice, it remains unknown whether EA catabolism is BMC dependent. Here, we provide evidence for BMC-dependent anaerobic EA utilization via metabolic analysis, proteomics and electron microscopy. First, we show B12-induced activation of theeutoperon inL. monocytogenescoupled to uptake and utilization of EA thereby enabling growth. Next, we demonstrate BMC formation in conjunction to EA catabolism with the production of acetate and ethanol in a molar ratio of 2:1. Flux via the ATP generating acetate branch causes an apparent redox imbalance due to reduced regeneration of NAD+ in the ethanol branch resulting in a surplus of NADH. We hypothesize that the redox imbalance is compensated by linkingeutBMC to anaerobic flavin-based extracellular electron transfer (EET). UsingL. monocytogeneswild type, a BMC mutant and a EET mutant, we demonstrate an interaction between BMC and EET and provide evidence for a role of Fe3+as an electron acceptor. Taken together, our results suggest an important role of anaerobic BMC-dependent EA catabolism in the physiology ofL. monocytogenes, with a crucial role for the flavin-based EET system in redox balancing.IMPORTANCEListeria monocytogenesis a food-borne pathogen causing severe illness and, as such, it is crucial to understand the molecular mechanisms contributing to pathogenicity. One carbon source that allowsL. monocytogenesto grow in humans is ethanolamine (EA), which is derived from phospholipids present in eukaryotic cell membranes. It is hypothesized that EA utilization occurs in bacterial microcompartments (BMCs), self-assembling subcellular proteinaceous structures and analogs of eukaryotic organelles. Here, we demonstrate that BMC-driven utilization of EA inL. monocytogenesresults in increased energy production essential for anaerobic growth. However, exploiting BMCs and the encapsulated metabolic pathways also requires balancing of oxidative and reductive pathways. We now provide evidence thatL. monocytogenescopes with this by linking BMC activity to flavin-based extracellular electron transfer (EET) using iron as an electron acceptor. Our results shed new light on an important molecular mechanism that enablesL. monocytogenesto grow using host-derived phospholipid degradation products.
Reverse Genetics with a Full-length Infectious cDNA Clone of Bovine Torovirus
Authors: Makoto Ujike , Yuka Etoh , Naoya Urushiyama , Fumihiro Taguchi , Luis Enjuanes , Wataru Kamitani 
Published: October 2020

AbstractTorovirus (ToV) has recently been classified in the new family Tobaniviridae, although it belonged to the Coronavirus (CoV) family historically. Reverse genetics systems for many CoVs have been established, but none exist for ToVs. Here, we describe a reverse genetics system using a full-length infectious cDNA clone of bovine ToV (BToV) in a bacterial artificial chromosome (BAC). Recombinant BToV containing genetic markers had the same phenotype as wild-type (wt) BToV. To generate two types of recombinant virus, the Hemagglutinin-esterase (HE) gene was manipulated, since cell-adapted wtBToV generally loses the full-length HE (HEf), resulting in soluble HE (HEs). First, recombinant viruses with HEf and HA-tagged HEf or HEs genes were rescued; these showed no significant differences in cell growth, suggesting that HE is not essential for viral growth in cells. Then, recombinant virus in which HE was replaced by the Enhanced Green Fluorescent Protein (EGFP) gene expressed EGFP in infected cells, but showed significantly reduced viral growth compared to wtBToV. Moreover, the recombinant virus readily deleted the EGFP gene after one passage. Interestingly, one variant with mutations in non-structural proteins (NSPs) showed improved EGFP expression and viral growth during serial passages, although it eventually deleted the EGFP gene, suggesting that these mutations contributed to EGFP gene acceptance. These recombinant viruses provide new insights regarding BToV and its reverse genetics will help advance understanding of this neglected pathogen.ImportanceToVs are diarrhea-causing pathogens that have been detected in many species, including humans. BToV has spread worldwide, leading to economic losses. We developed the first reverse genetics system for Tobaniviridae using a BAC-based BToV. Using this system, we showed that recombinant BToVs with HEf and HEs showed no significant differences in cell growth. In contrast, clinical BToVs generally lose the HE gene after a few passages but some recombinant viruses retained the HE gene for up to 20 passages, suggesting some benefits of HE retention. The EGFP gene of the recombinant viruses was unstable and was rapidly deleted, likely via negative selection. Interestingly, one virus variant with mutations in NSPs was more stable, resulting in improved EGFP-expression and viral growth, suggesting that the mutations contributed to some acceptance of the exogenous EGFP gene without clear positive selection. The recombinant BToVs and reverse genetics developed here are powerful tools for understanding fundamental viral processes and their pathogenesis and for developing BToV vaccines.
Role of managerial perception of competitive pressures in firms' product innovation success
Authors: Medhi Pankaj Kumar , Allamraju Ashita 
Published: October 2020

PurposeThis study explores the link between the level of importance managers assign to competitive pressures from domestic competition, foreign competition and customers as factors in the key business decisions related to innovation and the outcome of firms' product innovation efforts.Design/methodology/approachThe research sample is taken from the Business Environment and Enterprise Performance Survey by World Bank (2005). The relevant questions for the study were extracted from the survey. Logistic regression models were used for analysis using the ISLR library from R statistical software.FindingsManagers' consideration of customer pressure for innovation as important in key business decisions related to innovation has a positive and sustainable effect, distinct from that of R&D and other innovative activities, on firms' success of product innovation efforts.Research limitations/implicationsThe research acknowledges the need to verify the findings in a multicountry setting.Practical implicationsThis research can help mediate the managers' assignment of importance to certain types of competition for innovation decisions in multicompetitive environment for improved success of product innovation efforts.Originality/valueSimultaneous consideration of multiple competitive pressures by managers helps to identify the most suitable innovation activities for their respective firms and improve the chances of success of firms' innovation efforts.