bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK2 activity determines the timing of cell-cycle commitment and sequential DNA replication
Authors: Kim Sungsoo , Leong Alessandra , Nayar Chellam , Kim Minah , Yang Hee Won 
Published: June 2020

AbstractTo enter the cell cycle, mammalian cells must cross a point of no return (the commitment point), after which they proceed through the cell cycle regardless of changes in external signaling. This process is tightly regulated by the cyclin-dependent kinases (CDKs) and downstream molecules such as retinoblastoma (Rb). Here we show that CDK2 activity coordinates the timing of cell-cycle commitment and DNA replication. CDK4/6 activation initiates Rb phosphorylation and E2F activity, causing a gradual increase in CDK2 activity. Once CDK2 activity reaches a threshold level, CDK2 triggers the commitment point by maintaining Rb phosphorylation and subsequently initiates DNA replication. While the timing of the commitment point is tightly coupled with DNA replication, our experiments, which acutely increased CDK2 activity, suggest that the timing of the commitment point is before DNA replication. These findings highlight how cells utilize a safety mechanism to maintain genome stability by protecting against incomplete DNA replication.
Oxytocin excites BNST interneurons and inhibits BNST output neurons to the central amygdala
Authors: Francesconi Walter , Berton Fulvia , Olivera-Pasilio Valentina , Dabrowska Joanna 
Published: June 2020

AbstractThe dorsolateral bed nucleus of the stria terminalis (BNSTDL) has high expression of oxytocin (OT) receptors (OTR), which were shown to facilitate cued fear. However, the role of OTR in the modulation of BNSTDLactivity remains elusive. BNSTDLcontains GABA-ergic neurons classified based on intrinsic membrane properties into three types. Usingin vitropatch-clamp recordings in male rats, we demonstrate that OT selectively excites and increases spontaneous firing rate of Type I BNSTDLneurons. As a consequence, OT increases the frequency, but not amplitude, of spontaneous inhibitory post-synaptic currents (sIPSCs) selectively in Type II neurons, an effect abolished by OTR antagonist or tetrodotoxin, and reduces spontaneous firing rate in these neurons. These results suggest an indirect effect of OT in Type II neurons, which is mediated via OT-induced increase in firing of Type I interneurons. As Type II BNSTDLneurons were shown projecting to the central amygdala (CeA), we also recorded from retrogradelly labeled BNST→CeA neurons and we show that OT increases the frequency of sIPSC in these Type II BNST→CeA output neurons. In contrast, in Type III neurons, OT reduces the amplitude, but not frequency, of both sIPSCs and evoked IPSCs via a postsynaptic mechanism without changing their intrinsic excitability. We present a model of fine-tuned modulation of BNSTDLactivity by OT, which selectively excites BNSTDLinterneurons and inhibits Type II BNST→CeA output neurons. These results suggest that OTR in the BNST might facilitate cued fear by inhibiting the BNST→CeA neurons.HighlightsOxytocin directly excites and increases spontaneous firing of Type I BNST interneuronsOxytocin indirectly inhibits Type II BNST neuronsOxytocin inhibits Type II BNST output neurons to the central amygdala (BNST→CeA)Oxytocin reduces GABA-ergic transmission in Type III BNST neuronsOxytocin might facilitate cued fear by inhibiting the Type II BNST→CeA neuronsGraphical abstract
Vibrio campbelliichitoporin: thermostability study and implications for the development of therapeutic agents againstVibrioinfections
Authors: Aunkham Anuwat , Schulte Albert , Sim Wei Chung , Chumjan Watcharin , Suginta Wipa 
Published: June 2020

AbstractVibrio campbellii(formerlyVibrio harveyi) is a bacterial pathogen that causes vibriosis, which devastates fisheries and aquaculture worldwide.V. campbelliiexpresses chitinolytic enzymes and chitin binding/transport proteins, which serve as excellent targets for antimicrobial agent development. We previously characterizedVhChiP, a chitooligosaccharide-specific porin from the outer membrane ofV. campbelliiBAA-1116. This study employed far-UV circular dichroism and tryptophan fluorescence spectroscopy, together with single channel electrophysiology to demonstrate that the strong binding of chitoligosaccharides enhanced thermal stability ofVhChiP. The alanine substitution of Trp136at the center of the affinity sites caused a marked decrease in the binding affinity and decreased the thermal stability ofVhChiP. Tryptophan fluorescence titrations over a range of temperatures showed greater free-energy changes on ligand binding (ΔG°binding) with increasing chain length of the chitooligosaccharides. Our findings suggest the possibility of designing stable channel-blockers, using sugar-based analogs that serve as antimicrobial agents, active againstVibrioinfection.
Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity
Authors: Roland Bartholomew P. , Jain Bhawik K. , Graham Todd R. 
Published: June 2020

AbstractThe plasma membrane of a cell is characterized by an asymmetric distribution of lipid species across the exofacial and cytofacial aspects of the bilayer. The regulation of membrane asymmetry is a fundamental characteristic of membrane biology, and is crucial for signal transduction, vesicle transport, and cell division. The type-IV family of P-ATPases, or P4-ATPases, establish membrane asymmetry by selection and transfer of a subset of membrane lipids from the lumenal or exofacial leaflet to the cytofacial aspect of the bilayer. It is still unclear how these enzymes sort through the spectrum of lipids within the membrane to identify their desired substrate(s) and how the membrane environment modulates this activity. Therefore, we tested how the yeast plasma membrane P4-ATPase, Dnf2, responds to changes in membrane composition induced by perturbation of endogenous lipid biosynthetic pathways or exogenous application of lipid. The primary substrates of Dnf2 are two chemically divergent lipids, glucosylceramide (GlcCer) and phosphatidylcholine ((PC) or their lyso-lipid derivatives), and we find that these substrates compete with each other for transport. Acutely inhibiting sphingolipid synthesis using myriocin attenuates transport of exogenously applied GlcCer without perturbing PC transport. Deletion of genes controlling later steps of glycosphingolipid production also perturb GlcCer transport to a greater extent than PC transport. Surprisingly, application of lipids that are poor transport substrates differentially affect PC and GlcCer transport by Dnf2, thus altering substrate preference. Our data indicate that Dnf2 exhibits exquisite sensitivity to the membrane composition; thus, providing feedback onto the function of the P4-ATPases.
Structural basis ofBlastomycesEndoglucanase-2 adjuvancy in anti-fungal and -viral immunity
Authors: Santos Dias Lucas Dos , Dobson Hannah E. , Bakke Brock Kingstad , Kujoth Greg C. , Huang Junfeng , Kohn Elaine M. , Taira Cleison Ledesma , Wang Huafeng , Supekar Nitin T. , Azadi Parastoo , Li Lingjun , Suresh M. , Klein Bruce S. , Wüthrich Marcel 
Published: June 2020

ABSTRACTThe development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy,Blastomycesendoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+and CD8+T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit induced protective immunity against lethal influenza and fungal pulmonary challenge.AUTHOR SUMMARYFungal disease remains a challenging clinical and public health problem in part because there is no commercial vaccine available. The lack of suitable adjuvants is a critical barrier to developing safe and effective vaccines against fungal pathogens. Current adjuvants such as alum preferentially induce antibody responses which may be limited in mediating protection against fungi. Clinical observations and animal studies implicate cellular immunity as the essential component for the resolution of fungal infections. We have recently discovered an adjuvant that augments cell mediated immune responses and vaccine induced protection against fungi. Here, we identified the structural and mechanistic requirements by which this newly discovered adjuvant induces cell mediated immunity against fungi. As a proof of principle we also demonstrate that the adjuvant drives cellular immune responses against viruses such as influenza. We anticipate that our adjuvant can be used for vaccination with safe subunit vaccines against many microbial pathogens including viruses, intracellular bacteria, fungi and parasites that require cell mediated immune responses.
Systems genetics analyses in Diversity Outbred mice inform human bone mineral density GWAS and identifyQsox1as a novel determinant of bone strength
Authors: Al-Barghouthi Basel M. , Mesner Larry D. , Calabrese Gina M. , Brooks Daniel , Tommasini Steven M. , Bouxsein Mary L. , Horowitz Mark C. , Rosen Clifford J. , Nguyen Kevin , Haddox Samuel , Farber Emily A. , Onengut-Gumuscu Suna , Pomp Daniel , Farber Charles R. 
Published: June 2020

ABSTRACTGenome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we used Diversity Outbred (DO) mice to directly address these limitations by performing the first systems genetics analysis of 55 complex skeletal phenotypes. We applied a network approach to cortical bone RNA-seq data to discover 72 genes likely to be causal for human BMD GWAS associations, including the novel genesSERTAD4andGLT8D2. We also performed GWAS in the DO for a wide-range of bone traits and identifiedQsox1as a novel gene influencing cortical bone accrual and bone strength. Our results provide a new perspective on the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
Dopamine-related striatal neurophysiology is associated with specialization of frontostriatal reward circuitry through adolescence
Authors: Parr Ashley C. , Calabro Finnegan , Larsen Bart , Tervo-Clemmens Brenden , Foran Will , Olafsson Valur , Luna Beatriz 
Published: June 2020

SummaryCharacterizing developmental changes in frontostriatal circuitry is critical to our understanding of adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and sensation seeking, and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We combine longitudinal MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology with functional magnetic resonance imaging indices of resting-state and reward-state connectivity to investigate the contribution of dopaminergic processes to developmental changes in frontostriatal circuitry. Connectivity between the nucleus accumbens and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood. Nucleus accumbens tissue-iron mediated age-related changes and was associated with variability in connectivity. Our results provide evidence that developmental changes in dopamine-related striatal properties contribute to specialization of frontostriatal circuitry, potentially underlying changes in sensation seeking and reward sensitivity into adulthood.
Impact Of Covid-19 Pandemic On Mental Health Of Medical Students: A Cross-Sectional Study Using GAD-7 And PHQ-9 Questionnaires
Authors: Sartorão Filho Carlos Izaias , de Las Villas Rodrigues Wilson Conte , de Castro Ricardo Beauchamp , Marçal Arlete Aparecida , Pavelqueires Shirlene , Takano Luiz , de Oliveira Wilson Luis , Sartorão Neto Carlos Izaias 
Published: June 2020

AbstractAimto evaluate anxiety and depression disorders among medical students during COVID-19 pandemic.Methodscross-sectional study of medical students conducted in May 2020 with questionnaires regarding social and demographic status and GAD-7 for anxiety and PHQ-9 for depression questionnaires.Resultsparticipated 340 (97.98%) students. Average GAD-7 score was 9.18 (M = 9.18; SD = 4.75); average PHQ-9 score was 12.72 (M = 12.72; SD = 6.62). Results indicate a positive significant relationship between GAD-7 and females, and social distancing affecting finances. Using cut-off score of 10 for GAD-7, 157 (46.17%) students were identified with moderated or severe symptoms of anxiety. For PHQ-9 score, using cut-off of 10, 219 (64.41%) students were identified with moderate or severe symptoms of depression; results indicate a positive significant relationship between PHQ-9 and females and between social distancing affecting finances.Conclusionanalysis demonstrated a higher prevalence of moderated and severe anxiety and depression symptoms among medical students during COVID-19 pandemic, significantly among women and on medical students relating financial impairment related to COVID-19 epidemic.The project was approved by the Research Ethics Committee of Institution under report number CAAE: 30718220.5.0000.8547
Circuit mechanisms for chemical modulation of cortex-wide network interactions and exploration behavior
Authors: Pfeffer T. , Ponce-Alvarez A. , Meindertsma T. , Gahnström C. , van den Brink R. L. , Nolte G. , Tsetsos K. , Engel A.K. , Deco G. , Donner T.H. 
Published: June 2020

AbstractInfluential accounts postulate distinct roles of the catecholamine and acetylcholine neuromodulatory systems in cognition and behavior. But previous work found similar effects of these modulators on the response properties of individual cortical neurons. Here, we report a double dissociation between catecholamine and acetylcholine effects at the level of cortex-wide network interactions in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. Conversely, an acetylcholine-boost decreased correlations during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly altered by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted increased behavioral exploration, which we confirmed in human behavior during both a perceptual and value-based choice task. In sum, we identified specific circuit mechanisms for shaping cortex-wide network interactions and behavior by key neuromodulatory systems.
On the drivers of profitability in the banking industry in restructuring times: a Bayesian perspective
Authors: Cruz-García Paula , Forte Anabel , Peiró-Palomino Jesús 
Published: June 2020

PurposeThere is abundant literature analyzing the determinants of banks’ profitability through its main component: the net interest margin. Some of these determinants are suggested by seminal theoretical models and subsequent expansions. Others are ad-hoc selections. Up to now, there are no studies assessing these models from a Bayesian model uncertainty perspective. This paper aims to analyze this issue for the EU-15 countries for the period 2008-2014, which mainly corresponds to theGreat Recessionyears.Design/methodology/approachIt follows a Bayesian variable selection approach to analyze, in a first step, which variables of those suggested by the literature are actually good predictors of banks’ net interest margin. In a second step, using a model selection approach, the authors select the model with the best fit. Finally, the paper provides inference and quantifies the economic impact of the variables selected as good candidates.FindingsThe results widely support the validity of the determinants proposed by the seminal models, with only minor discrepancies, reinforcing their capacity to explain net interest margin disparities also during the recent period of restructuring of the banking industry.Originality/valueThe paper is, to the best of the knowledge, the first one following a Bayesian variable selection approach in this field of the literature.
Experimental and numerical analysis on using CuO-Al2O3/water hybrid nanofluid in a U-type tubular heat exchanger
Authors: Gürbüz Emine Yağız , Variyenli Halil İbrahim , Sözen Adnan , Khanlari Ataollah , Ökten Mert 
Published: June 2020

Purpose
Heat exchangers (HEXs) are extensively used in many applications such as heating and cooling systems. To increase the thermal performance of HEXs, nano-sized particles could be added to the base working fluid which can improve the thermophysical properties of the fluid. In addition, further improvement in the thermal performance of nanofluids can be obtained by using two or more different nanoparticles which are known as hybrid nanofluids. This paper aims to improve the thermal efficiency of U-type tubular HEX (THEX) by using CuO-Al2O3/water hybrid nanofluid.

Design/methodology/approach
Numerical simulation has been used to model THEX with various configurations. Also, CuO-Al2O3/water hybrid nanofluid has been experimented in THEX in two various modes including parallel (PTHEX) and counter flow (CTHEX) regarding to the numerical findings. Hybrid nanofluids have been prepared in two particle concentrations and compared with CuO/water nanofluid at the same concentrations and also with water.

Findings
The numerical simulation results showed that adding fins and also using hybrid nanofluid can increase heat transfer rate in HEX. However, adding fins cannot be a good option in U-type THEX with lower diameter because it increases pressure drop notably. Experimental results of this work illustrated that using Al2O3-CuO/water hybrid nanofluid in the THEX improved thermal performance significantly. Maximum enhancement in overall heat transfer coefficient of THEX by using CuO-Al2O3/water nanofluid in 0.5% and 1% concentrations achieved as 9.5% and 12%, respectively.

Originality/value
The obtained findings of the study showed the positive effects of using hybrid type nanofluid in comparison with single type nanofluid. In this study, numerical and experimental analysis have been conducted to investigate the effect of using hybrid type nanofluid in U-type HEX. The obtained results exhibited successful utilization of CuO-Al2O3/water hybrid type nanofluid in HEX. Moreover, it was observed that thermal performance analysis of the nanofluids without any experiment can be done by using numerical method.
A novel multi-dimensional features fusion algorithm for the EEG signal recognition of brain's sensorimotor region activated tasks
Authors: Wei Minghua , Lin Feng 
Published: June 2020

PurposeAiming at the shortcomings of EEG signals generated by brain's sensorimotor region activated tasks, such as poor performance, low efficiency and weak robustness, this paper proposes an EEG signals classification method based on multi-dimensional fusion features.Design/methodology/approachFirst, the improved Morlet wavelet is used to extract the spectrum feature maps from EEG signals. Then, the spatial-frequency features are extracted from the PSD maps by using the three-dimensional convolutional neural networks (3DCNNs) model. Finally, the spatial-frequency features are incorporated to the bidirectional gated recurrent units (Bi-GRUs) models to extract the spatial-frequency-sequential multi-dimensional fusion features for recognition of brain's sensorimotor region activated task.FindingsIn the comparative experiments, the data sets of motor imagery (MI)/action observation (AO)/action execution (AE) tasks are selected to test the classification performance and robustness of the proposed algorithm. In addition, the impact of extracted features on the sensorimotor region and the impact on the classification processing are also analyzed by visualization during experiments.Originality/valueThe experimental results show that the proposed algorithm extracts the corresponding brain activation features for different action related tasks, so as to achieve more stable classification performance in dealing with AO/MI/AE tasks, and has the best robustness on EEG signals of different subjects.
“I was trying to speak to their human side” coping responses of Belgium’s undocumented migrants to barriers in health-care access
Authors: Lafaut Dirk , Coene Gily 
Published: June 2020

PurposeUndocumented migrants experience major legal constraints in their health-care access. Little is known on how undocumented migrants cope with these limitations in health-care access as individuals. The purpose of this study is to explore the coping responses of undocumented migrants when they experience limited health-care access in face-to-face encounters with health-care providers.Design/methodology/approachThe authors conducted multi-site ethnographic observations and 25 semi-structured in-depth interviews with undocumented migrants in Belgium. They combined the “candidacy model” of health-care access with models from coping literature on racism as a framework. The candidacy model allowed them to understand access to health care as a dynamic and interactive negotiation process between health-care workers and undocumented migrants.FindingsResponses to impaired health-care access can be divided into four main strategies: (1) individuals can react with a self-protective response withdrawing from seeking further care; (2) they can get around the obstacle; (3) they can influence the health-care worker involved by deploying discursive or performative skills; or (4) they can seek to confront the source of the obstacle.Research limitations/implicationsThese findings point to the importance of care relations and social networks, as well as discursive and performative skills of undocumented migrants when negotiating barriers in access to health care.Originality/valueThis study refines the candidacy model by highlighting how individuals respond on a micro-level to shifts towards exclusionary health policies and, by doing so dynamically, change provision of health-care services.