bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHOSPHO1, a novel skeletal regulator of insulin resistance and obesity
Authors: Suchacki KJ , Morton NM , Vary C , Huesa C , Yadav MC , Thomas BJ , Rajoanah S , Bunger L , Ball D , Barrios-Llerena M , Guntur AR , Khavandgar Z , Cawthorn WP , Ferron M , Karsenty G , Murshed M , Rosen CJ , MacRae VE , Millán JL , Farquharson C 
Published: May 2020

AbstractThe skeleton is recognised as a key endocrine regulator of metabolism. Here we show that mice lacking the bone mineralization enzyme PHOSPHO1 (Phospho1-/-) exhibited improved basal glucose homeostasis and resisted high-fat-diet induced weight gain and diabetes. The metabolic protection inPhospho1-/-mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated fromPhospho1-/-mice were enriched for genes associated with energy metabolism and diabetes;Phospho1both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adultPhospho1-/-mice. However, the decreased serum choline levels inPhospho1-/-mice were normalized by feeding a 2% choline rich diet resulting in a normalization in insulin sensitivity and fat mass. This study identifies PHOSPHO1 as a potential therapeutic target for the treatment of obesity and diabetes.
Removal of the extracellular matrix biases auditory cortical layer dynamics towards supragranular frequency integration
Authors: El-Tabbal M , Niekisch H , Henschke JU , Budinger E , Frischknecht R , Deliano M , Happel MFK 
Published: May 2020

AbstractIn the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity. However, the underlying impact of local removal of the ECM on cortical circuit processing is still not understood. Here, we removed the ECM in the primary auditory cortex (ACx) of adult Mongolian gerbils using local injections of hyaluronidase (HYase). Using laminar current-source density (CSD) analysis, we found layer-specific changes of the spatiotemporal synaptic activity patterns. Applying multitaper spectral analysis and time-domain conditional Granger causality (GC) measures, we found increased stimulus-evoked oscillatory power in the beta band (25-36 Hz) selectively within infragranular layers Vb and enhanced supragranular synaptic activity. Our findings reveal new insights on how ECM modulation affects the sensory integration via altered translaminar cortical network dynamics with a supragranular lead of the columnar response profile.
Machine learning prediction of particle-size distribution from infrared spectra, methodologies and soil features
Authors: Parent Elizabeth J. , Parent Serge-É. , Parent Léon E. 
Published: May 2020

AbstractAccuracy of infrared (IR) models to measure soil particle-size distribution (PSD) depends on soil preparation, methodology (sedimentation, laser), settling times and relevant soil features. Compositional soil data may require log ratio (ilr) transformation to avoid numerical biases. Machine learning can relate numerous independent variables that may impact on NIR spectra to assess particle-size distribution. Our objective was to reach high IRS prediction accuracy across a large range of PSD methods and soil properties. A total of 1298 soil samples from eastern Canada were IR-scanned. Spectra were processed by Stochastic Gradient Boosting (SGB) to predict sand, silt, clay and carbon. Slope and intercept of the log-log relationships between settling time and suspension density function (SDF) (R2= 0.84-0.92) performed similarly to NIR spectra using eitherilr-transformed (R2= 0.81-0.93) or raw percentages (R2= 0.76-0.94). Settling times of 0.67-min and 2-h were the most accurate for NIR predictions (R2= 0.49-0.79). The NIR prediction of sand sieving method (R2= 0.66) was more accurate than Bouyoucos (R2= 0.53). The NIR 2X gain was less accurate (R2= 0.69-0.92) than 4X (R2= 0.87-0.95). The MIR (R2= 0.45-0.80) performed better than NIR (R2= 0.40-0.71) spectra. Adding soil carbon, reconstituted bulk density, pH, red-green-blue color, oxalate and Mehlich3 extracts returned R2value of 0.86-0.91 for texture prediction. In addition to slope and intercept of the SDF, 4X gain, method and pre-treatment classes, soil carbon and color appeared to be promising features for routine SGB-processed NIR particle-size analysis.Soil Classification(Soil Taxonomy): Inceptisols, Spodosols
Potential Impact of Climate Change on One-Horned Rhinoceros (Rhinoceros unicornis) in Nepal
Authors: Adhikari Ayush , Shah Deep Narayan 
Published: May 2020

AbstractAbrupt change in climate or simply termed as climate change is considered to be one of the major challenges in biodiversity. Change in climate has impacted many species around the world, particularly threatened species like One-Horned Rhinoceros (Rhinoceros unicornis).Rhinoceros unicornisis placed as an endangered species by International Union for Conservation of Nature (IUCN). Being an endangered species, studies regarding the impact of climate on the distribution ofRhinoceros unicornisis very rare in Nepal. Thus, the present study focuses on identifying the potential impact of climate change on the suitable habitat ofRhinoceros unicornisin Nepal using Species Distribution Modelling (SDM). For this, we used the present climatic scenarios and two greenhouse concentration trajectories (RCP 4.5 and RCP 8.5) for two different time periods (2050 and 2070) using different bioclimatic variables. Our model demonstrated the loose of the suitable habitat ofRhincoeros unicornisby 51.87% and 56.54% in RCP 4.5 for year 2050 and 2070 respectively. Under RCP 8.5 for year 2050 and 2070, the model demonstrated the loose of present suitable habitat by 54.25% and 49.51% respectively. Likewise, our result also predicted elevation as an important bioclimatic variable. This study would provide an information to the policy makers, conservationist and government officer of Nepal for the management and protection of habitat ofRhinoceros unicornisin present and future climatic context.
Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions
Authors: Rimington Rowan P. , Fleming Jacob W. , Capel Andrew J. , Wheeler Patrick C. , Lewis Mark P. 
Published: May 2020

AbstractInvestigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals and model organisms. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable temporal investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Separate maturation of primary human skeletal muscle and iPSC derived motor neurons seeks to accurately represent neuromuscular development via controlled addition of motor axons following primary myogenesis. Spheroid cultures of motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ∼400, ∼150 and ∼200-fold respectively. Axon projections of adhered motor neuron spheroids exceeded 1000μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced in a concentration dependent manner within optimised 3D type I collagen extracellular matrices. Bioengineered skeletal muscles produce functional forces, demonstrate increased acetylcholine receptor (AChR) clustering, and transcription of MUSK and LRP4 mRNAs indicating enhanced organisation of the post-synaptic membrane. Dosed integration of motor neuron spheroids outlined the motor pool required to functionally innervate muscle tissues in 3D, generating physiologically functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve terminal co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Finally, functional analyses outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling of NMJs within innervated motor units.
Ustilago maydisserves as a novel production host for the synthesis of plant and fungal sesquiterpenoids
Authors: Lee Jungho , Hilgers Fabienne , Loeschke Anita , Jaeger Karl-Erich , Feldbrügge Michael 
Published: May 2020

AbtractSesquiterpenoids are important secondary metabolites with various pharma- and nutraceutical properties. In particular, higher basidiomycetes possess a versatile biosynthetic repertoire for these bioactive compounds. To date, only a few microbial production systems for fungal sesquiterpenoids have been established. Here, we introduceUstilago maydisas a novel production host. This model fungus is a close relative of higher basidiomycetes. It offers the advantage of metabolic compatibility and potential tolerance for substances toxic to other microorganisms. We successfully implemented a heterologous pathway to produce the carotenoid lycopene that served as a straightforward read-out for precursor pathway engineering. Overexpressing genes encoding enzymes of the mevalonate pathway resulted in increased lycopene levels. Verifying the subcellular localisation of the relevant enzymes revealed that initial metabolic reactions might take place in peroxisomes: despite the absence of a canonical peroxisomal targeting sequence, acetyl-CoA C-acetyltransferase Aat1 localised to peroxisomes. By expressing the plant (+)-valencene synthase CnVS and the basidiomycete sesquiterpenoid synthase Cop6, we succeeded in producing (+)-valencene and α-cuprenene, respectively. Importantly, the fungal compound yielded about tenfold higher titres in comparison to the plant substance. This proof of principle demonstrates thatU. maydiscan serve as promising novel chassis for the production of terpenoids.
Cooperative foraging during larval stage affects fitness inDrosophila
Authors: Dombrovski Mark , Kuhar Rives , Mitchell Alexandra , Shelton Hunter , Condron Barry 
Published: May 2020

SummaryCooperative behavior can confer advantages to animals. This is especially true for cooperative foraging which provides fitness benefits through more efficient acquisition and consumption of food. While examples of group foraging have been widely described, the principles governing formation of such aggregations and rules that determine group membership remain poorly understood. Here we take advantage of an experimental model system featuring cooperative foraging behavior inDrosophila. Under crowded conditions, fly larvae form coordinated digging groups (clusters), where individuals are linked together by sensory cues and group membership requires prior experience. However, fitness benefits ofDrosophilalarval clustering remain unknown. We demonstrate that animals raised in crowded conditions on food partially processed by other larvae experience a developmental delay presumably due to the decreased nutritional value of the substrate. Intriguingly, same conditions promote formation of cooperative foraging clusters which further extends larval stage compared to non-clustering animals. Remarkably, this developmental retardation also results in a relative increase in wing size, serving an indicator of adult fitness. Thus, we find that the clustering-induced developmental delay is accompanied by fitness benefits. Therefore, cooperative foraging, while delaying development, may have evolved to giveDrosophilalarvae benefits when presented with competition for limited food resources.
Fenchel duality of Cox partial likelihood and its application in survival kernel learning
Authors: Wilson Christopher M. , Li Kaiqiao , Sun Qiang , Kuan Pei Fen , Wang Xuefeng 
Published: May 2020

AbstractThe Cox proportional hazard model is the most widely used method in modeling time-to-event data in the health sciences. A common form of the loss function in machine learning for survival data is also mainly based on Cox partial likelihood function, due to its simplicity. However, the optimization problem becomes intractable when more complicated regularization is employed with the Cox loss function. In this paper, we show that a convex conjugate function of Cox loss function based on Fenchel Duality exists, and this provides an alternative framework to optimization based on the primal form. Furthermore, the dual form suggests an efficient algorithm for solving the kernel learning problem with censored survival outcomes. We illustrate the application of the derived duality form of Cox partial likelihood loss in the multiple kernel learning setting
Regulation of light harvesting in multimeric and monomeric photosystem II supercomplexes
Authors: Kim Eunchul , Watanabe Akimasa , Duffy Christopher D. P. , Ruban Alexander V. , Minagawa Jun 
Published: May 2020

ABSTRACTAn intriguing architecture called ‘semi-crystalline photosystem II (PSII) array’ has been observed in the thylakoid membranes in vascular plants. It is an array of PSII–light harvesting complex II (LHCII) supercomplexes only appears in the low-light, whose functional role has not been clarified. We identified PSII–LHCII supercomplexes in their monomeric and multimeric forms in the low-light acclimated spinach leaves and prepared them using sucrose density gradient-ultracentrifugation in the presence of amphipol A8-35. When the leaves were acclimated to high-light, however, only monomeric forms were present. Single particle electron microscopy identified that the multimeric PSII–LHCII supercomplexes were composed of two (‘megacomplex’) or three (‘arraycomplex’) units of PSII–LHCII supercomplexes, which aligned like a fraction of the semi-crystalline array. Further characterization using fluorescence analysis revealed that multimeric forms have a higher light-harvesting capability, but a lower thermal dissipation capability than the monomeric form, suggesting such a configurational conversion of PSII–LHCII supercomplexes possibly serves as a structural basis for the plants’ acclimation to environmental light.
Dynamics of primitive streak regression controls the fate of neuro-mesodermal progenitors in the chicken embryo
Authors: Guillot Charlene , Michaut Arthur , Rabe Brian , Pourquié Olivier 
Published: May 2020

AbstractIn classical descriptions of vertebrate development, the segregation of the three embryonic germ layers is completed by the end of gastrulation. Body formation then proceeds in a head to tail fashion by progressive deposition of lineage committed progenitors during regression of the Primitive Streak (PS) and tail bud (Pasteels, 1937b; Stern, 2004). Identification of Neuro-Mesodermal Progenitors (NMPs) contributing to both musculo-skeletal precursors (paraxial mesoderm) and spinal cord during axis formation by retrospective clonal analysis challenged these notions (Henrique et al., 2015; Tzouanacou et al., 2009). However, in amniotes such as mouse and chicken, the precise identity and localization of these cells has remained unclear despite a wealth of fate mapping analyses of the PS region. Here, we use lineage tracing in the chicken embryo to show that single cells located in the SOX2/T positive anterior PS region contribute to both neural and mesodermal lineages in the trunk and tail, but only express this bipotential fate with some delay. We demonstrate that posterior to anterior gradients of convergence speed and ingression along the PS gradually lead to exhaustion of all mesodermal precursor territories except for NMPs where limited ingression and increased proliferation maintain and amplify this pool of axial progenitors. As a result, most of the remaining mesodermal precursors from the PS in the tail bud are bipotential NMPs. Together, our results provide a novel understanding of the contribution of the PS and tail bud to the formation of the body of amniote embryos.
Small-molecule sensitization of RecBCD helicase-nuclease to a Chi hotspot-activated state
Authors: Karabulut Ahmet C. , Cirz Ryan T. , Smith Gerald R. 
Published: May 2020

ABSTRACTCoordination of multiple activities of complex enzymes is critical for life, including transcribing, replicating, and repairing DNA. Bacterial RecBCD helicase-nuclease must coordinate DNA unwinding and cutting to repair broken DNA. Starting at a DNA end, RecBCD unwinds DNA with its fast RecD helicase on the 5’-ended strand and its slower RecB helicase on the 3’-ended strand. At Chi hotspots (5’GCTGGTGG3’), RecB’s nuclease cuts the 3’-ended strand and loads RecA strand-exchange protein onto it. We report here that a small molecule NSAC1003, a sulfanyltriazolobenzimidazole, mimics Chi sites by sensitizing RecBCD to cut DNA at a Chi-independent position a certain percent of the DNA substrate’s length. This percent decreases with increasing NSAC1003 concentration. Our data indicate that NSAC1003 slows RecB and sensitizes it to cut DNA when the leading helicase RecD stops at the DNA distal end. Two previously described RecBCD mutants altered in the RecB ATP-binding site also have this property, but uninhibited wild-type RecBCD lacks it. Computation docks NSAC1003 into the ATP-binding site, suggesting that NSAC1003 acts directly on RecB. NSAC1003 will help elucidate the molecular mechanisms of RecBCD-Chi regulation and DNA repair. Similar studies could help elucidate other DNA enzymes whose activities are coordinated at chromosomal sites.
Susceptibility trends of zoliflodacin against multidrug-resistantNeisseria gonorrhoeaeclinical isolates in Nanjing, China (2014-2018)
Authors: Le Wenjing , Su Xiaohong , Lou Xiangdi , Li Xuechun , Gong Xiangdong , Wang Baoxi , Genco Caroline A. , Mueller John P. , Rice Peter A. 
Published: May 2020

ABSTRACTPreviously, we reported potent activity of a novel spiropyrimidinetrione, zoliflodacin, againstN. gonorrhoeaeisolates from symptomatic men in Nanjing, China, collected in 2013. Here, we investigated trends of susceptibilities of zoliflodacin in 986 gonococcal isolates collected from men between 2014 and 2018.N. gonorrhoeaeisolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations ingyrA, gyrB, parCandparEgenes were determined by PCR and DNA sequencing. The MIC of zoliflodacin forN. gonorrhoeaeranged from ≤0.002 to 0.25 mg/L; the overall MIC50s and MIC90s were 0.06 mg/L and 0.125mg/L in 2018, increasing two-fold from 2014. However, the percent of isolates with lower zoliflodacin MICs declined in each year sequentially while the percent with higher MICs increased yearly (P≤0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥1 μg/ml); 21.2% (209/986) were resistant to azithromycin (≥1 μg/ml), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) tetracycline-resistant (TRNG) and 19.4% (191/986) were multi-drug resistant (MDR) isolates. Among 143 isolates with higher zoliflodacin MICs (0.125-0.25 mg/L), all had quinolone resistance associated double or triple mutations ingyrA; 139/143 (97.2%) also had mutations inparC. There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; a S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin has excellentin vitroactivity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin and extended spectrum cephalosporins.
Early Short Course Corticosteroids in Hospitalized Patients with COVID-19
Authors: Fadel Raef , Morrison Austin R. , Vahia Amit , Smith Zachary R. , Chaudhry Zohra , Bhargava Pallavi , Miller Joseph , Kenney Rachel M. , Alangaden George , Ramesh Mayur S. ,   Henry Ford COVID-19 Management Task Force
Published: May 2020

AbstractBackgroundThere is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19.MethodsWe conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of pre and post-corticosteroid groups were evaluated. A composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality was the primary outcome measure. All patients had at least 14 days of follow-up.ResultsWe analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in pre-and post-corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in post-corticosteroid group compared to pre-corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was observed in the post-corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.45; 95% CI [0.25 – 0.81]).ConclusionAn early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.SummaryIn this multi-center quasi-experimental study of 213 patients, we demonstrate early short course of methylprednisolone in moderate to severe COVID-19 patients reduced the composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality.
MALVIRUS: an integrated web application for viral variant calling
Authors: Ciccolella Simone , Denti Luca , Bonizzoni Paola , Vedova Gianluca Della , Pirola Yuri , Previtali Marco 
Published: May 2020

AbstractBeing able to efficiently call variants from the increasing amount of sequencing data daily produced from multiple viral strains is of the utmost importance, as demonstrated during the COVID-19 pandemic, in order to track the spread of the viral strains across the globe.We present MALVIRUS, an easy-to-install and easy-to-use web application that assists users in two tasks:computing a variant catalog consisting in a set of population SNP loci from the population sequences andefficiently calling variants of the catalog from a read sample.Tests on Illumina and Nanopore samples prove the efficiency and the effectiveness of MALVIRUS in genotyping SARS-CoV-2 strain samples with respect to GISAID data.
How strategy environment and wealth shape altruistic behaviour: Cooperation rules affecting wealth distribution in dynamic networks
Authors: Pathak Spandan , Verma Prateek , Ram Sumit K. , Sengupta Supratim 
Published: May 2020

AbstractSocieties rely on individual contributions to sustain public goods that benefit the entire community. Several mechanisms, that specify how individuals change their decisions based on past experiences, have been proposed to explain how altruists are not outcompeted by selfish counterparts. A key aspect of such strategy updates involves a comparison of an individual’s latest payoff with that of a random neighbour. In reality, both the economic and social milieu often shapes cooperative behaviour. We propose a new decision heuristic, where the propensity of an individual to cooperate depends on the local strategy environment in which she is embedded as well as her wealth relative to that of her neighbours. Our decision-making model allows cooperation to be sustained and also explains the results of recent experiments on social dilemmas in dynamic networks. Final cooperation levels depend only on the extent to which the strategy environment influences altruistic behaviour but are largely unaffected by network restructuring. However, the extent of wealth inequality in the community is affected by a subtle interplay between the environmental influence on a person’s decision to contribute and the likelihood of reshaping social ties, with wealth-inequality levels rising with increasing likelihood of network restructuring in some situations.