bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Mechanistic Characterization of a Peptide Inhibitor of Glycogen Synthase Kinase (GSK3β) Derived from the Disrupted in Schizophrenia 1 (DISC1) Protein
Authors: Saundh Stephanie , Patnaik Debasis , Gagné Steve , Bishop Josh , Lipsit Sean , Amat Samat , Pujari Narsimha , Nambisan Anand Krishnan , Bigsby Robert , Murphy Mary , Tsai Li-Huei , Haggarty Stephen , Leung Adelaine Kwun-Wai 
Published: June 2020

ABSTRACTGlycogen Synthase Kinase 3-beta (GSK3β) is a critical regulator of several cellular pathways involved in neuroplasticity and is a potential target for neurotherapeutic development in the treatment of neuropsychiatric and neurodegenerative diseases. The majority of efforts to develop inhibitors of GSK3β have been focused on developing small molecule inhibitors that compete with ATP through direct interaction with the ATP binding site. This strategy has presented selectivity challenges due to the evolutionary conservation of this domain within the kinome. The Disrupted in Schizophrenia (DISC1) protein, has previously been shown to bind and inhibit GSK3β activity. Here, we report the characterization of a 44-mer peptide derived from human DISC1 (hDISCtide) that is sufficient to both bind and inhibit GSK3β in a non-competitive mode that is distinct from classical ATP competitive inhibitors. Based on multiple independent biochemical and biophysical assays, we propose that hDISCtide interacts at two distinct regions of GSK3β: an inhibitory region that partially overlaps with the binding site of FRATide, a well-known GSK3β binding peptide, and a specific binding region that is unique to hDISCtide. Taken together, our findings present a novel avenue for developing a peptide-based selective inhibitor of GSK3β.
Monogamy in a moment: how do brief social interactions change over time in pair-bonded zebra finches (Taeniopygia guttata)?
Authors: Prior Nora H. , Smith Edward , Dooling Robert J. , Ball Gregory F. 
Published: June 2020

AbstractResearch on monogamy has largely focused on marked behaviors that are unique to pair bonded partners. However, these marked behaviors represent only a subset of the pair-directed behaviors that partners engage in; the influence of pair bonding on mundane or subtle social interactions among partners remains largely unknown. In the current study, we describe the changes that occur during brief social reunions (or greets) over the course of pair bonding in zebra finches. We quantified pair-directed behavior during five-minute reunions from three stages of pair bonding: initial pairing (between 4-72 hrs), early pairing (1-2 weeks) and late pairing (>1 month). These social interactions were operationalized in multiples ways. First, we quantified the overall activity levels (call and movement rates) for both the male and female. Overall, females were more active than males, but for both males and females calling activity was highest during the initial timepoint (between 4-72 hrs post-pairing). We quantified behavioral coordination between partners in two ways, 1) similarity in call and movement rates between partners, and 2) temporal synchrony between calls and movements (via sliding correlation coefficients of time-stamped calls and movements). Overall there were no effects of pairing on behavioral coordination. Finally, we used principal component analyses to disentangle behavioral coordination from the activity levels of the male and female. These results contribute to a growing line of evidence that male and female zebra finches differentially contribute to social dynamics and highlight the influence of pair bonding on the development of social dynamics. Behavioral coordination is clearly important for marked interactions (e.g. duetting, courtship displays and biparental care). Our results raise the question of what the roles of such mundane social interactions are in monogamous partnerships.
Host cell factors important for BHV-1 cell entry revealed by genome-wide CRISPR knockout screen
Authors: Tan Wenfang Spring , Rong Enguang , Dry Inga , Lillico Simon , Law Andy , Whitelaw Bruce , Dalziel Robert G. 
Published: June 2020

AbstractIn order to identify host factors that impact Bovine Herpes Virus Type 1 (BHV-1) infection we previously applied a genome wide CRISPR knockout screen with a library covering all bovine protein coding genes. We compiled a list of both pro-viral and anti-viral proteins involved in BHV-1 replication; here we provide further analysis of those that are potentially involved in viral entry into the host cell. These entry related factors include the cell surface proteins PVR and PVRL2, a group of enzymes directly or indirectly associated with the biosynthesis of Heparan Sulfate Proteoglycans (HSPG), and proteins that reside in the Golgi apparatus engaging in intra-Golgi trafficking. For the first time, we provide evidence that PVRL2 serves a receptor for BHV-1, mediating more efficient entry than the previously identified PVR. By knocking out two enzymes that catalyze HSPG chain elongation, HST2ST1 and GLCE, we demonstrated the significance of HSPG in BHV-1 entry. Another intriguing cluster of genes, COG1, COG2 and COG4-7 encodes for six subunits of the conserved oligomeric Golgi (COG) complex. MDBK cells lacking COG6 were less infectable by BHV-1 but release newly produced virions more efficiently as evidenced by fewer but bigger plaques compared to control cells, suggesting impaired HSPG biosynthesis. To facilitate candidate validation, we devised a one-step multiplex CRISPR interference (CRISPRi) system named CRISPR3i that enables quick and simultaneous deployment of three CRISPRs for efficient gene inactivation. Using CRISPR3i, we verified an additional 23 candidates, with many implicated in cellular entry.
Analyzing changes in respiratory rate to predict the risk of COVID-19 infection
Authors: Miller Dean J. , Capodilupo John V. , Lastella Michele , Sargent Charli , Roach Gregory D. , Lee Victoria H. , Capodilupo Emily R. 
Published: June 2020

ABSTRACTCOVID-19, the disease caused by the SARS-CoV-2 virus, can cause shortness of breath, lung damage, and impaired respiratory function. Containing the virus has proven difficult, in large part due to its high transmissibility during the pre-symptomatic incubation. The study’s aim was to determine if changes in respiratory rate could serve as a leading indicator of SARS-CoV-2 infections. A total of 271 individuals (age = 37.3 ± 9.5, 190 male, 81 female) who experienced symptoms consistent with COVID-19 were included – 81 tested positive for SARS-CoV-2 and 190 tested negative; these 271 individuals collectively contributed 2672 samples (days) of data (1856 healthy days, 231 while infected with COVID-19 and 585 while infected with something other than COVID-19). To train a novel algorithm, individuals were segmented as follows; (1) a training dataset of individuals who tested positive for COVID-19 (n=57 people, 537 samples); (2) a validation dataset of individuals who tested positive for COVID-19 (n=24 people, 320 samples) ; (3) a validation dataset of individuals who tested negative for COVID-19 (n=190 people, 1815 samples). All data was extracted from the WHOOP system, which uses data from a wrist-worn strap to produce validated estimates of respiratory rate and other physiological measures. Using the training dataset, a model was developed to estimate the probability of SARS-CoV-2 infection based on changes in respiratory rate during night-time sleep. The model’s ability to identify COVID-positive individuals not used in training and robustness against COVID-negative individuals with similar symptoms were examined for a critical six-day period spanning the onset of symptoms. The model identified 20% of COVID-19 positive individuals in the validation dataset in the two days prior to symptom onset, and 80% of COVID-19 positive cases by the third day of symptoms.
Performance characterization of PCR-free whole genome sequencing for clinical diagnosis
Authors: Zhang Ningzhi , Zhou Meizhen , Zeng Fanwei , Wang Xiaodan , Liu Fengxia , Qiao Zhihong , Fan Chunna , Wang Yaoshen , Fang Zhonghai , Dai Wentao , Xiang Jiale , Sun Jun , Peng Zhiyu , Song Lijie , Sun Yan 
Published: June 2020

AbstractPurposeTo evaluate the performance of PCR-free whole genome sequencing (WGS) for clinical diagnosis, and thereby revealing how experimental parameters affect variant detection.MethodsAll the 5 NA12878 samples were sequenced using MGISEQ-2000. NA12878 samples underwent WGS with differing DNA input and library preparation protocol (PCR-based versus PCR-free protocols for library preparation). The DP (depth of coverage) and GQ (genotype quality) of each sample were compared. We developed a systematic WGS pipeline for the analysis of down-sampling samples of the 5 NA12878 samples. The performance of each sample was measured for sensitivity, coverage of depth and breadth of coverage of disease-related genes and CNVs.ResultsIn general, NA12878-2 (PCR-free WGS) showed better DP and GQ distribution than NA12878-1 (PCR-based WGS). With a mean depth of ~40X, the sensitivity of homozyous and heterozygous SNPs of NA12878-2 showed higher sensitivity (>99.77% and > 99.82%) than NA12878-1, and positive predictive value (PPV) exceeded 99.98% and 99.07%. The sensitivity and PPV of homozygous and heterozygous indels for NA12878-2 (PCR-free WGS) showed great improvement than NA128878-1. The breadths of coverage for disease-related genes and CNVs are slightly better for samples with PCR-free library preparation protocol than the sample with PCR-based library preparation protocol. DNA input also influences the performance of variant detection in samples with PCR-free WGS.ConclusionDifferent experimental parameters may affect variant detection for clinical WGS. Clinical scientists should know the range of sensitivity of variants for different methods of WGS, which would be useful when interpreting and delivering clinical reports.
The Structure-Based Virtual Screening for Natural Compounds that Bind with the Activating Receptors of Natural Killer Cells
Authors: Rowaiye Adekunle Babajide , Oni Solomon , Uzochukwu Ikemefuna Chijioke , Akpa Alex , Esimone Charles Okechukwu 
Published: June 2020

AbstractAimThis study is aimed at prospecting for natural compounds that have strong binding affinity for the Activating Receptors of Natural Killer (NK) cells.BackgroundNK cells are responsible for the immunosurveillance of tumor and virally- infected cells. The cytotoxic potentials of this unique population of immune cells are triggered by the activating receptors. Through ligand-binding, these receptors induce the tyrosine phosphorylation of adapter proteins through their Immunoreceptor Tyrosine–based Activation Motif ITAM sequences and this triggers direct cytotoxicity and the production of cytokines through different signal pathways.ObjectiveTo computationally predict the selectivity, specificity, and efficacy of natural compounds to be used as immunostimulatory agents for cancer treatment.MethodIn this study, 1,697 natural compounds were obtained from 82 edible tropical plants through data mining. The molecular docking simulations of these compounds were executed against 18 activating NK cells receptor targets using the Python Prescription 0.8. An arbitrary docking score ≥ −7.0 kcal/mol was chosen as cut off value. Further screening for oral bioavailability, promiscuity, molecular complexity and pharmacokinetic properties using the Swissadme and pkCSM webservers. The ligand similarity analysis and phylogenetic analysis of the receptors was carried out with the ChemMine and Clustal Omega webservers respectively. Binding site analyses and bioactivity prediction were also done with the Protein-Ligand Interaction Profiler and Molinspiration webservers respectively. Normal mode analyses were carried out with the CABS-flex 2.0 server.ResultSeventeen bioactive and non-promiscuous lead compounds with good physicochemical and pharmacokinetic properties were identified.ConclusionFurther tests are required to evaluate the efficacy of the lead compounds.
Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window
Authors: Gouveia Duarte , Miotello Guylaine , Gallais Fabrice , Gaillard Jean-Charles , Debroas Stéphanie , Bellanger Laurent , Lavigne Jean-Philippe , Sotto Albert , Grenga Lucia , Pible Olivier , Armengaud Jean 
Published: June 2020

AbstractRapid but yet sensitive, specific and high-throughput detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples is key to diagnose infected people and to better control the spread of the virus. Alternative methodologies to PCR and immunodiagnostic that would not require specific reagents are worth to investigate not only for fighting the COVID-19 pandemic, but also to detect other emergent pathogenic threats. Here, we propose the use of tandem mass spectrometry to detect SARS-CoV-2 marker peptides in nasopharyngeal swabs. We documented that the signal from the microbiota present in such samples is low and can be overlooked when interpreting shotgun proteomic data acquired on a restricted window of the peptidome landscape. Simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC-MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. We argue that peptides ADETQALPQR and GFYAQGSR from the nucleocapsid protein are of utmost interest as their signal is intense and their elution can be obtained within a 3 min window in the tested conditions. These results pave the way for the development of time-efficient viral diagnostic tests based on mass spectrometry.
Single cell reconstruction of human basal cell diversity in normal and IPF lung
Authors: Carraro Gianni , Mulay Apoorva , Yao Changfu , Mizuno Takako , Konda Bindu , Petrov Martin , Lafkas Daniel , Arron Joe R. , Hogaboam Cory M. , Chen Peter , Jiang Dianhua , Noble Paul W. , Randell Scott H. , McQualter Jonathan L. , Stripp Barry R. 
Published: June 2020

AbstractRationaleDeclining lung function in patients with interstitial lung disease is accompanied by epithelial remodeling and progressive scarring of the gas-exchange region. There is a need to better understand the contribution of basal cell hyperplasia and associated mucosecretory dysfunction to the development of idiopathic pulmonary fibrosis (IPF).ObjectivesWe sought to decipher the transcriptome of freshly isolated epithelial cells from normal and IPF lung to discern disease-dependent changes within basal stem cells.MethodsSingle cell RNA sequencing was used to map epithelial cell types of the normal and IPF human airway. Organoid and ALI cultures were used to investigate functional properties of basal cell subtypes.Measurements and Main ResultsWe found that basal cells included multipotent and secretory primed subsets in control adult lung tissue. Secretory primed basal cells include an overlapping molecular signature with basal cells obtained from distal lung tissue of IPF lungs. We confirmed that NOTCH2 maintains undifferentiated basal cells and restrict basal-to-ciliated differentiation, and present evidence that NOTCH3 functions to restrain secretory differentiation.ConclusionsBasal cells are dynamically regulated in disease and are specifically biased towards expansion of the secretory primed basal cell subset in idiopathic pulmonary fibrosis. Modulation of basal cell plasticity may represent a relevant target for therapeutic intervention in IPF.
The changing nature of consumer animosity and cosmopolitanism among young, individualistic consumers in emerging Asia: evidence from China
Authors: Han C. Min , Wang Xiao , Nam Hyojin 
Published: June 2020

PurposeThis study is designed to address how rising individualism in emerging Asia changes consumer values and subsequent consumer behavior toward foreign brands. For this, we investigate consumer animosity (CA) and consumer cosmopolitanism (COS) in China and their impacts on consumer dispositions toward Japanese brands.Design/methodology/approachThe study hypothesizes that CA and COS mediate the effects of consumer individualism and age on brand attitudes and purchase intentions. Online surveys were conducted with 421 consumers in China.FindingsThe results indicate that consumers with individualistic values show favorable dispositions toward Japanese brands because of weak CA and strong COS values. In addition, the study found that younger consumers also harbor weak CA and do not avoid Japanese brands because of it. However, younger consumers were not found to be more cosmopolitan than their older counterparts.Originality/valueOur findings suggest that the modernization and individualization of a society can have impacts on consumer values in emerging Asia and that changes in consumer values among young and individualistic consumers can lead to increased preferences for foreign brands, especially brands from a country with historical animosity.
Consumer finance/household finance: the definition and scope
Authors: Xiao Jing Jian , Tao Chunsheng 
Published: June 2020

PurposeThe purpose of this literature review paper is to define consumer finance, describe the scope of consumer finance and discuss its future research directions.Design/methodology/approachIn this paper, consumer finance is used as a synonym of household finance. Consumers refer to individuals and families. After defining the term “consumer finance,” we conducted a critical review of consumer finance as an interdisciplinary research field in terms of money managing, insuring, borrowing and saving/investing. Future research directions are also discussed.FindingsThis paper discusses similarities and differences among several terms such as consumer finance, household finance, personal finance, family finance and behavioral finance. The paper also reviewed key studies on consumer financial behavior around four key financial functions, namely, money management, insurance, loan and saving/investment and several nontraditional topics such as fintech and financial capability/literacy. The paper also introduced several datasets of consumer finance commonly used in the United States and China.Originality/valueThis paper clarified several similar terms related to consumer finance and sorted out the diverse literature of consumer finance in multiple disciplines such as economics, finance and consumer science, which provide a foundation for generating more fruitful research in consumer finance in the future.
Effects of open innovation strategies on innovation performance of SMEs: evidence from China
Authors: Lu Chang , Yu Bo , Zhang Jing , Xu Dan 
Published: June 2020

PurposeThe purpose of this study is to investigate the relationships between two types of open innovation (OI) strategies (OI breadth and depth) and innovation performance of small- and medium-sized enterprises (SMEs) in China. The study examines how firms’ absorptive capacity and government institutional support affect these relationships.Design/methodology/approachSurvey data from 236 manufacturing SMEs in China were used to test the proposed model using hierarchical regression analysis.FindingsThe results show that both OI breadth and depth are positively related to innovation performance of SMEs. Moreover, this study finds that realized absorptive capacity serves as a mediator in the relationships between OI breadth and depth and innovation performance. The potential absorptive capacity and government institutional support moderate the relationship between OI breadth and innovation performance.Originality/valueThe effectiveness of OI strategies is significantly different among SMEs. One possible explanation is that SMEs adopt different types of OI strategies. Another is that a firm’s absorptive capacity and government institutional support may influence the effectiveness of OI. This study integrates these two possible reasons by investigating the effect of the interplay between different OI strategies, absorptive capacity and government institutional support on SMEs’ innovation performance. This study enriches the research on the relationships between OI strategies and innovation performance of SMEs in the Chinese context.
Personality, occupational sorting and routine work
Authors: Viinikainen Jutta , Böckerman Petri , Elovainio Marko , Hakulinen Christian , Hintsanen Mirka , Kähönen Mika , Pehkonen Jaakko , Pulkki-Råback Laura , Raitakari Olli , Keltikangas-Järvinen Liisa 
Published: June 2020

PurposeA prominent labour market feature in recent decades has been the increase in abstract and service jobs, while the demand for routine work has declined. This article examines whether the components of Type A behaviour predict workers' selection into non-routine abstract, non-routine service and routine jobs.Design/methodology/approachBuilding on the work by Barrick et al. (2013), this article first presents how the theory of purposeful work behaviour can be used to explain how individuals with different levels of Type A components sort into abstract, service and routine jobs. Then, using longitudinal data, it examines whether the components of Type A behaviour predict occupational sorting. Estimations were performed based on the linear regression method.FindingsThe results show that the Type A dimension “leadership” was associated with a higher level of abstract and service job tasks in occupation. High eagerness-energy and responsibility were also positively linked with occupation's level of abstract tasks. These results suggest that workers sort into jobs that allow them to pursue higher-order implicit goals.Originality/valueJob market polarisation towards low-routine jobs has had a pervasive influence on the labour market during the past few decades. Based on high-quality data that combine prime working-age register information on occupational attainment with information about personality characteristics, the findings contribute to our knowledge of how personality characteristics contribute to occupational sorting in terms of this important job aspect.
Evaluating the satisfaction rate for affordable housing in non-gated residential area (NGR): the case of Al-Sharq housing project in Zarqa-Jordan
Authors: Al Shawabkeh Rami Khaled , Alzouby Ahmad M. , Rjoub Abdelmajeed , Alsmadi Mays , AlKhamaiseh Maram , Shboul Deema , Smadi Ahmad , Al-Bzour Ahmad , Al-Omari Rawan , Alobaidat Esraa 
Published: June 2020

PurposeNon-gated residential communities (NGR) are now becoming significant in Jordan resulting in an increase in low and medium-income areas. This study aims to investigate the sense of community at residential level within NGR by testing the characteristics presented in the first and largest non-gated community in Jordan (Al-Sharq project).Design/methodology/approachSuch characteristics were identified via literary reviews and visual data collected through site visits, observation and photographs of the project's physical settings. This formed the basis of a questionnaire/survey that was distributed to the residents. This research depends on the mixed-method approach (qualitative and quantitative) to achieve the research objectives. The quantitative method involved the use of a questionnaire/survey, while the qualitative method undertook a comparative process using some statistical methods for the main characteristics. The results were analysed by using descriptive statistics, comprising frequency and factor analyses.FindingsThe study concludes with a framework consisting of suggestions and recommendations to remove the main constraints on improving the quality of life for the non-gated residential community.Practical implicationsThe outcome of this study will influence the decisions made by the parties involved in urban development in Jordan when designing residential neighborhoods.Originality/valueThe significance of this paper is that while the majority of studies have been on the evaluation of gated communities in developing countries, there have only been a limited of studies specifically examining the experience of residents in those environments. Therefore, this paper contributes and adds to the existing knowledge in the development of non-gated communities in a developing country.