bluuebunny/crossref_metadata_2025_split huggingface dataset:
The primary motor cortex prospectively computes the spinal reflex
Authors: Umeda Tatsuya , Isa Tadashi , Nishimura Yukio 
Published: June 2020

AbstractThe spinal reflex transforms sensory signals to generate muscle activity. However, it is unknown how the motor cortex (MCx) takes the spinal reflex into account when performing voluntary limb movements. We simultaneously recorded the activity of the MCx, afferent neurons, and forelimb muscles in behaving monkeys. We decomposed muscle activity into subcomponents explained by the MCx or afferent activity using linear models. Long preceding activity in the MCx, which is responsible for subsequent afferent activity, had the same spatiotemporal contribution to muscle activity as afferent activity, indicating that the MCx drives muscle activity not only by direct descending activation but also by trans-afferent descending activation. Therefore, the MCx implements internal models that prospectively estimate muscle activation via the spinal reflex for precise movement control.
Anin vitroassessment of anti-SARS-CoV-2 activity of oral preparations of iodine complexes (RENESSANS)
Authors: Altaf Imran , Nadeem Muhammad Faisal , Hussain Nadir , Nawaz Muhammad , Raza Sohail , Ali Muhammad Asad , Hasan Sohail , Matti Nazish , Ashraf Muhammad , Ulla Ihsan , Fazal Sehar , Rafique Saira , Adnan Muhammad , Sardar Nageen , Khan Tahir , Moavia Muhammad , Ashraf Sohaib , Tahir Zarfishan , Mukhtar Nadia , Yaqub Tahir 
Published: June 2020

ABSTRACTSince the emergence of CoVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determinedIn Vitroanti-SARS-CoV-2 activity of oral formulations (syrup and capsule) of an Iodine-complex (Renessans). A monolayer of vero cells were exposed to SARS-CoV-2 in the presence and absence of different concentrations (equivalent to 50, 05 and 0.5 μg/ml of I2) of Renessans. Anti-SARS-CoV-2 activity of each of the formulation was assessed in the form of cell survival, SARS-CoV-2-specific cytopathic effect (CPE) and genome quantization. With varying concentrations of syrup and capsule, a varying rate of inhibition of CPE, cells survival and virus replication was observed. Compared to 0.5 μg/ml concentration of Renessans syrup, 5 and 50 μg/ml showed comparable results where there was a 100% cell survival, no CPEs and a negligible viral replication (ΔCT= 0.11 and 0.13, respectively). This study indicates that Renessans, containing iodine, may have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.
Predicting clinical drug response from model systems by non-linear subspace-based transfer learning
Authors: Mourragui Soufiane , Loog Marco , Vis Daniel J. , Moore Kat , Manjon Anna G. , van de Wiel Mark A. , Reinders Marcel J.T. , Wessels Lodewyk F.A. 
Published: June 2020

AbstractPre-clinical models have been the workhorse of cancer research for decades. While powerful, these models do not fully recapitulate the complexity of human tumors. Consequently, translating biomarkers of drug response from pre-clinical models to human tumors has been particularly challenging. To explicitly take these differences into account and enable an efficient exploitation of the vast pre-clinical drug response resources, we developed TRANSACT, a novel computational framework for clinical drug response prediction. First, TRANSACT employs non-linear manifold learning to capture biological processes active in pre-clinical models and human tumors. Then, TRANSACT builds predictors on cell line response only and transfers these to Patient-Derived Xenografts (PDXs) and human tumors. TRANSACT outperforms four competing approaches, including Deep Learning approaches, for a set of 15 drugs on PDXs, TCGA cohorts and 226 metastatic tumors from the Hartwig Medical Foundation data. For only four drugs Deep Learning outperforms TRANSACT. We further derived an algorithmic approach to interpret TRANSACT and used it to validate the approach by identifying known biomarkers to targeted therapies and we propose novel putative biomarkers of resistance to Paclitaxel and Gemcitabine.
Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states
Authors: Girbig Mathias , Misiaszek Agata D. , Vorländer Matthias K. , Lafita Aleix , Grötsch Helga , Baudin Florence , Bateman Alex , Müller Christoph W. 
Published: June 2020

ABSTRACTRNA polymerase III (Pol III) synthesises tRNAs and other short, essential RNAs. Human Pol III misregulation is linked to tumour transformation, neurodegenerative and developmental disorders, and increased sensitivity to viral infections. Pol III inhibition increases longevity in different animals but also promotes intracellular bacterial growth owing to its role in the immune system. This highlights the importance to better understand human Pol III transcription on a molecular level. Here, we present cryo-EM structures at 2.8 to 3.3 Å resolution of transcribing and unbound human Pol III purified from human suspension cells that were gene-edited by CRISPR-Cas9. We observe insertion of the TFIIS-like subunit RPC10 into the polymerase funnel, providing insights into how RPC10 triggers transcription termination. Our structures also resolve elements absent from S. cerevisiae Pol III such as the winged-helix domains of RPC5 and an iron-sulphur cluster in RPC6, which tethers the heterotrimer subcomplex to the Pol III core. The cancer-associated RPC7α isoform binds the polymerase clamp, potentially interfering with Pol III inhibition by the tumour suppressor MAF1, which may explain why overexpressed RPC7α enhances tumour transformation. Finally, the human Pol III structure allows mapping of disease-related mutations and might contribute to developing inhibitors that selectively target Pol III for therapeutic interventions.
microbialPhenotypes: An R package that analyzes high-throughput microbial phenotype data
Authors: Wu Peter I-Fan , Hu James C. , Siegele Deborah A. 
Published: June 2020

AbstractVarious microbial high-throughput phenotyping techniques have been vastly conducted to infer functions of genes, generating large numbers of valuable datasets whose potential in providing insights to characterize genes hasn’t been fully exploited. Therefore, computational tools that allow unbiased, systematic analysis of these data also have become vital. Here we describe a package that evaluates high-throughput microbial phenotype data by one or several sets of associated functional annotations are provided. In addition, some helper functions are provided to help clean high-throughput microbial phenotype data.
Real-Time Measurement of Stimulated Dopamine Release in Compartments of the AdultDrosophila melanogasterMushroom Body
Authors: Shin Mimi , Copeland Jeffrey M. , Venton B. Jill 
Published: June 2020

AbstractDrosophila melanogaster, the fruit fly, is an exquisite model organism to understand neurotransmission. Dopaminergic signaling in theDrosophilamushroom body (MB) is involved in olfactory learning and memory, with different compartments controlling aversive learning (corner) vs appetitive learning (medial tip). Here, the goal was to develop techniques to measure endogenous dopamine in compartments of the MB for the first time. We compared three stimulation methods: acetylcholine (natural stimulus), P2X2(chemogenetics), and CsChrimson (optogenetics). Evoked dopamine release was measured with fast-scan cyclic voltammetry in isolated adultDrosophilabrains. Acetylcholine stimulated the largest dopamine release (0.40 μM), followed by P2X2(0.14 μM), and CsChrimson (0.07 μM). With the larger acetylcholine and P2X2stimulations, there were no regional or sex differences in dopamine release. However, with CsChrimson, dopamine release was significantly higher in the corner than the medial tip, and females had more dopamine than males. Michaelis-Menten modeling of the single-light pulse revealed no significant regional differences in Km, but the corner had a significantly lower Vmax(0.12 μM/s vs. 0.19 μM/s) and higher dopamine release (0.05 μM vs. 0.03 μM). Optogenetic experiments are challenging because CsChrimson is also sensitive to blue light used to activate green fluorescent protein, and thus, light exposure during brain dissection must be minimized. These experiments expand the toolkit for measuring endogenous dopamine release inDrosophila, introducing chemogenetic and optogenetic experiments for the first time. With a variety of stimulations, different experiments will help improve our understanding of neurochemical signaling inDrosophila.
Baclofen decreases compulsive alcohol drinking in rats characterised by reduced levels of GAT-3 in the central amygdala
Authors: Marti-Prats Lucia , Belin-Rauscent Aude , Fouyssac Maxime , Puaud Mickaёl , Cocker Paul J. , Everitt Barry J. , Belin David 
Published: June 2020

AbstractWhile most individuals with access to alcohol drink it recreationally, about 5 % lose control over their intake and progressively develop an alcohol use disorder (AUD), characterised by compulsive alcohol drinking accompanied by decreased interest in alternative sources of reinforcement. The neural and molecular mechanisms underlying the vulnerability to switch from controlled to compulsive alcohol intake have not been fully characterized, so limiting the development of new treatments for AUD. It has recently been shown that rats having reduced levels of expression of the gamma-aminobutyric acid (GABA) transporter, GAT-3, in the amygdala tend to persist in seeking and drinking alcohol even when adulterated with quinine, suggesting that pharmacological interventions aimed at restoring GABA homeostasis in these individuals may provide a targeted treatment to limit compulsive alcohol drinking. Here, we tested the hypothesis that the GABABreceptor agonist baclofen, which decreases GABA release, specifically decreases compulsive alcohol drinking in vulnerable individuals. In a large cohort of Sprague-Dawley rats allowed to drink alcohol under an intermittent two-bottle choice procedure, a cluster of individuals was identified that persisted in drinking alcohol despite adulteration or the availability of an alternative ingestive reinforcer, saccharin. In these rats, that were characterised by decreased GAT-3 mRNA levels in the central amygdala, acute baclofen administration (1.5 mg/kg, intraperitoneal) resulted in a decrease in compulsive drinking. These results indicate that low GAT-3 mRNA levels in the central amygdala represent an endophenotype of AUD and that the associated compulsive alcohol drinking characteristic is sensitive to baclofen.
Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase
Authors: Chen Zhuoyao , Zhang Jinwei , Heilig Raphael , Sorrell Fiona J. , D’Angiolella Vincenzo , Fischer Roman , Alessi Dario R. , Bullock Alex N. 
Published: June 2020

AbstractThe BTB-Kelch protein KLHL3 is a Cullin3-dependent E3 ligase that mediates the ubiquitin-dependent degradation of kinases WNK1-4 to control blood pressure and cell volume. A crystal structure of KLHL3 has defined its binding to an acidic degron motif containing a PXXP sequence that is strictly conserved in WNK1, WNK2 and WNK4. Mutations in the second proline abrograte the interaction causing the hypertension syndrome pseudohypoaldosteronism type II. WNK3 shows a diverged degron motif containing 4 amino acid substitutions that remove the PXXP motif raising questions as to the mechanism of its binding. To understand this atypical interaction, we determined the crystal structure of the KLHL3 Kelch domain in complex with a WNK3 peptide. The electron density enabled the complete 11-mer WNK-family degron motif to be traced for the first time revealing several conserved features not captured in previous work, including additional salt bridge and hydrogen bond interactions. Overall, the WNK3 peptide adopted a conserved binding pose except for a subtle shift to accommodate bulkier amino acid substitutions at the binding interface. At the centre, the second proline was substituted by WNK3 Thr541, providing a unique phosphorylatable residue among the WNK-family degrons. Fluorescence polarisation and structural modelling experiments revealed that its phosphorylation would abrogate the KLHL3 interaction similarly to hypertension-causing mutations. Together, these data reveal how the KLHL3 Kelch domain can accommodate the binding of multiple WNK isoforms and highlight a potential regulatory mechanism for the recruitment of WNK3.
Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study
Authors: Norris Rachael P. , Terasaki Mark 
Published: June 2020

AbstractGap junctions have well-established roles in cell-cell communication by way of forming permeable intercellular channels. Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Here, we systematically studied the fate of connexosomes in intact ovarian follicles. High pressure frozen, serial sectioned tissue was immunogold labeled for Connexin 43. Within a volume of electron micrographs, every labeled structure was categorized and counted. Surface area measurements indicate that large connexosomes undergo fission. Subsequent modifications are separation of inner and outer membranes, loss of Cx43 from the outer membrane, and outward budding of the modified membranes. We also documented several clear examples of organelle transfer from one cell to another by gap junction internalization. We discuss how connexosome formation and processing may be a novel means for gap junctions to mediate cell-cell communication.
Overexpression ofblaOXA-58Gene Driven by ISAba3is Associated with Imipenem Resistance in a ClinicalAcinetobacter baumanniiIsolate from Vietnam
Authors: Nguyen Anh T. , Pham Son C. , Ly Anh K. , Nguyen Chau V.V. , Vu Thanh T. , Ha Tuan M. 
Published: June 2020

AbstractThe aim of this study was to investigate genetic structures and expression ofblaOXA-58 gene in fiveAcinetobacter baumanniiclinical isolates recovered from two hospitals in southern Vietnam during 2012-2014.A. baumanniiisolates were identified by automated microbiology systems and confirmed by PCR. All isolates were characterized as multidrug resistant by antimicrobials testing using the disk diffusion method. Four imipenem susceptible and one non-susceptible isolates (MIC > 32μg.ml−1) were identified by E-test. PCR amplification ofblaOXA-58gene upstream and downstream sequences revealed the presence of ISAba3at both locations in one multidrug resistant isolate. Semi quantitation ofblaOXA-51andblaOXA-58gene expression was performed by the 2−ΔΔCtmethod. TheblaOXA-51gene expression of five isolates showed little difference but the isolate bearing ISAba3-blaOXA-58-ISAba3exhibited significant higherblaOXA-58mRNA level. Higher β-lactamases activity in periplasmic than cytoplasmic fraction was found in most isolates. The isolate overexpressingblaOXA-58 gene possessed very high periplasmic enzyme activity. In conclusion, theA. baumanniiisolate bearing ISAba3-blaOXA-58gene exhibited high resistance to imipenem, corresponding to an overexpression ofblaOXA-58gene and very high periplasmic β-lactamases activity.
Changes to the growth and discount rates and asset impairment
Authors: Georges Maxeem 
Published: June 2020

Purpose
With timeliness and measurement of asset impairments as well as management opportunistic behaviour being topical, since the issuance of Australian Accounting Standards Board (AASB) 136, this study aims to examine whether assumptions about growth and discount rates made about asset recoverable amounts determine asset impairments.

Design/methodology/approach
This study uses a sample of 450 firm-year observations representing 133 Australian listed firms from 2015 to 2018. An estimation model is used where asset impairments is the dependent variable, growth and discount rates are the variables of interest and several impairment indicators are included as controls.

Findings
The results show that the decrease in growth rate but not the increase in discount rate affects the recognition of large asset impairments, where firms decrease the growth rate in the year of recognition. A change in discount rate affects asset impairments only when it is higher than the industry average. Hence, the growth rate is the management’s tool of choice in the recognition of asset impairments.

Originality/value
This study provides additional insight into how AASB 136 is used in practice. This includes investigating the tools used by firms in the calculation of asset recoverable amount and whether firms provide important information, as a part of disclosure. The results are of interest to investors and policymakers because they highlight the need for more restrictions around growth rate assumptions and less variation in disclosure.
A model of traditional functional food consumption behaviour
Authors: Sumaedi Sik , Sumardjo  
Published: June 2020

PurposeThis study aims to analyse the influence of descriptive norm, perceived behavioural control, perceived threat of non-communicable disease (NCD), healthy food extension education frequency, the frequency of healthy food community group meetings, healthy food-related newspapers/magazines usage frequency, healthy food-related websites usage frequency and healthy food-related social media usage frequency towards traditional functional food consumption behaviour, especially tempeh, in Indonesia.Design/methodology/approachThis study collected data from 99 respondents who consumed traditional functional food. The data were analysed using multiple regression.FindingsTraditional functional food consumption behaviour is significantly influenced by descriptive norm, perceived behavioural control and the frequency of healthy food community group meetings. The traditional functional food consumption behaviour is not affected by the perceived threat of NCD, healthy food extension education frequency, healthy food-related newspapers/magazines usage frequency, healthy food-related websites usage frequency and healthy food-related social media usage frequency.Research limitations/implicationsThis research investigated only one functional food type and employed a purposive sampling technique. Future research should be conducted in other contexts to examine the stability of the research findings.Practical implicationsTo improve traditional functional food consumption, it is essential to ensure that people can easily consume traditional functional food. It is also essential to develop an extension education strategy that involves the community's influential person/leader and healthy food community group meetings.Originality/valueThis paper is the first that investigates traditional functional foods consumption behaviour.
The impact of perceived stress on US millennials' external and emotional eating behavior
Authors: Okumus Bendegul , Ozturk Ahmet Bulent 
Published: June 2020

PurposeThe purpose of this paper is to identify the relationship between Millennials' perceived stress and their external and emotional eating behaviors. Furthermore, the moderating effect of nutritional knowledge on the relationship between perceived stress and emotional eating and perceived stress and external eating of US Millennials was tested.Design/methodology/approachData was collected from 649 Millennials between the ages of 18 and 35 in the United States, and structural equation modeling (SEM) was performed to test the study hypotheses.FindingsThis study extends the literature and provides further insights into the relationship between US Millennials' eating behavior and stress factors. Perceived stress positively influenced Millennials' emotional and external eating behavior, and nutritional knowledge significantly moderated the relationships between perceived stress and emotional eating and perceived stress and external eating.Research limitations/implicationsFirst, data was collected from Millennials living in the United States. Second, not all of the predictors, save one (perceived stress), were selected and hypothesized as predictors of Millennials' eating behavior. The paper provides the essential psychological elements of US Millennials' eating behavior.Originality/valueIf unbalanced eating and obesity are the result of negative psychological factors, the recommended diet models or physical exercise by themselves may be less effective at combating obesity and related health issues. This is because stress was found to be a highly significant reason for unbalanced eating, new and more practical stress coping strategies are needed to moderate unbalanced eating behavior.
Empirical approach to the sequential relationships between generation, relational capital and performance in family wineries in Spain
Authors: Fernandez-Olmos Marta , Diaz-Vial Isabel , Malorgio Giulio 
Published: June 2020

PurposeThis study aims to focus on relational social capital in family wineries. Relational social capital is influenced by the family nature of the business and is at the same time a key antecedent of winery performance. The aim is to analyse these relationships in the qualified denomination of origin (DOC) Rioja wine industry (Spain).Design/methodology/approachUsing a final sample of 110 family wineries, a Baron and Kenny approach was performed to investigate the causal and mediating relationships between the generation in control, relational social capital and family winery performance.FindingsUsing a final sample of 110 family wineries, the study demonstrates that later generations show a higher level of relational social capital, that the positive relationship between relational social capital and performance is maintained in a family firm sample and that the generation in control sequentially influence on performance through its influence on relational social capital.Research limitations/implicationsThe main limitations are that empirical data were obtained only from DOC Rioja wine family businesses and a cross-sectional study was conducted.Social implicationsThis study provides policymakers and family managers responsible for succession with a better understanding of the effects of transferring the business to the next generations in terms of relational social capital and performance.Originality/valueTo the best of the knowledge, this is the first study to examine the sequential relationships between generation, relational social capital and performance in DOC Rioja family wineries. The context of the DOC Rioja wine industry is particularly noteworthy for two reasons. First, in this industry, family-controlled firms predominate. Second, the DOC Rioja wine industry is focussed on the small-to-medium context, which has conventionally provided a very good area for the development of social capital theory.