bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice
Authors: Gul Seref , Akyel Yasemin Kubra , Gul Zeynep Melis , Isin Safak , Korkmaz Tuba , Selvi Saba , Danis Ibrahim , Ipek Ozgecan Savlug , Aygenli Fatih , Taskin Ali Cihan , Ozturk Nuri , Ozturk Narin , Ünal Durişehvar Özer , Guzel Mustafa , Turkay Metin , Okyar Alper , Kavakli Ibrahim Halil 
Published: July 2021

AbstractCryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous level of the CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis is unknown. Here, we discovered a molecule that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The small molecule, called M47, selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and the period of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 enhanced degradation rate of the CRY1 level in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced cisplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Finally, systemic repetitive administration of M47 increased the median lifespan of p53−/− mice by ~25%. Collectively our data suggest that M47 is a very promising molecule to treat forms of cancer depending on the p53 mutation.
Emergence of growth and dormancy from a kinetic model of theEscherichia colicentral carbon metabolism
Authors: Himeoka Yusuke , Mitarai Namiko 
Published: July 2021

AbstractPhysiological states of bacterial cells exhibit a wide spectrum of timescale. Under nutrient-rich conditions, most of the cells in an isogenic bacterial population grow at certain rates, while a small subpopulation sometimes falls into a dormant state where the growth rates slow down by orders of magnitude. The dormant cells have unique characteristics: The metabolic activity is quite slow, and the dormant cells typically exhibit a high tolerance for a range of stresses, such as antibiotics applications. To reveal the origins of such heterogeneity of timescales, we constructed a kinetic model ofEscherichia colicentral carbon metabolism, including the dynamics of the energy currency molecules, and asked if perturbations of the metabolites’ concentrations lead to the distinct metabolic states. By numerically studying the relaxation dynamics, we found that the model robustly exhibits two qualitatively distinct relaxation dynamics depending on the initial conditions generated by the perturbations. In the first type, the concentrations of metabolites reach the steady-state quickly, resembling the growing dynamics. On the other hand, the other type of dynamics takes a much longer time to reach the steady-state, and during the relaxation, cell growth almost halts, reminding us of the dormant cells. In order to unveil the mechanism of distinct behaviors, we reduced the metabolic network model into a minimal model without losing the emergence of distinct dynamics. Analytical and numerical studies of the 2-variable minimal model revealed the necessary conditions for the distinct behavior, namely, the depletion of energy due to the futile cycle and its non-uniform impact on the kinetics because of the coexistence of the energy currency-coupled and uncoupled reactions as well as branching of the network. The result is consistent with the experimental reports that the dormant cells commonly exhibit low ATP levels and provides a possible explanation for the appearance of dormant cells that causes antibiotic persistence.
Modelling the spatiotemporal spread of beneficial alleles using ancient genomes
Authors: Muktupavela Rasa , Petr Martin , Ségurel Laure , Korneliussen Thorfinn , Novembre John , Racimo Fernando 
Published: July 2021

AbstractAncient genome sequencing technologies now provide the opportunity to study natural selection in unprecedented detail. Rather than making inferences from indirect footprints left by selection in present-day genomes, we can directly observe whether a given allele was present or absent in a particular region of the world at almost any period of human history within the last 10,000 years. Methods for studying selection using ancient genomes often rely on partitioning individuals into discrete time periods or regions of the world. However, a complete understanding of natural selection requires more nuanced statistical methods which can explicitly model allele frequency changes in a continuum across space and time. Here we introduce a method for inferring the spread of a beneficial allele across a landscape using two-dimensional partial differential equations. Unlike previous approaches, our framework can handle time-stamped ancient samples, as well as genotype likelihoods and pseudohaploid sequences from low-coverage genomes. We apply the method to a panel of published ancient West Eurasian genomes to produce dynamic maps showcasing the inferred spread of candidate beneficial alleles over time and space. We also provide estimates for the strength of selection and diffusion rate for each of these alleles. Finally, we highlight possible avenues of improvement for accurately tracing the spread of beneficial alleles in more complex scenarios.
A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection
Authors: Goffin Emeline , Hemmi Silvio , Machiels Bénédicte , Gillet Laurent 
Published: July 2021

AbstractThe development of effective and flexible vaccine platforms is a major public health challenge as recently highlighted by the COVID-19 pandemic. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally as demonstrated by the long-term use of oral AdV 4 and 7 vaccines in the US military. These viruses therefore appear to be the ideal backbone for the development of oral replicative vector vaccines. However, research on these vaccines is limited by the ineffective replication of human AdVs in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicative conditions. Here, we orally vaccinated mice with MAV-1 vectors expressing the full length or the “headless” hemagglutinin (HA) of influenza to assess the protection conferred against an intranasal challenge of influenza. We showed that while the headless HA vector did not generate a significant humoral or cellular immune response to influenza, a single oral immunisation with the full-length HA vaccine generated influenza-specific and neutralizing antibodies and completely protected the mice against clinical signs and viral replication.ImportanceGiven the constant threat of pandemics and the need for annual vaccination against influenza and possibly emerging agents such as SARS-CoV-2, new types of vaccines that are easier to produce and administer and therefore more widely accepted are a critical public health need. Here, using a relevant animal model, we have shown that replicative oral AdV vaccine vectors can help make vaccination against major respiratory diseases more available, better accepted and therefore more effective. These results could be of major importance in the coming years in the fight against emerging diseases such as COVID-19.
Dual projecting cells linking thalamic and cortical communication routes between the medial prefrontal cortex and hippocampus
Authors: Schlecht Maximilian , Jayachandran Maanasa , Rasch Gabriela E. , Allen Timothy A. 
Published: July 2021

AbstractThe interactions between the medial prefrontal cortex (mPFC) and the hippocampus (HC) are critical for memory and decision making and have been specifically implicated in several neurological disorders including schizophrenia, epilepsy, frontotemporal dementia, and Alzheimer’s disease. The ventral midline thalamus (vmThal), and lateral entorhinal cortex and perirhinal cortex (LEC/PER) constitute major communication pathways that facilitate mPFC-HC interactions in memory. Although vmThal and LEC/PER circuits have been delineated separately we sought to determine whether these two regions share cell-specific inputs that could influence both routes simultaneously. To do this we used a dual fluorescent retrograde tracing approach using cholera toxin subunit-B (CTB-488 and CTB-594) with injections targeting vmThal and the LEC/PER in rats. Retrograde cell body labeling was examined in key regions of interest within the mPFC-HC system including: (1) mPFC, specifically anterior cingulate cortex (ACC), dorsal and ventral prelimbic cortex (dPL, vPL), and infralimbic cortex (IL); (2) medial and lateral septum (MS, LS); (3) subiculum (Sub) along the dorsal-ventral and proximal-distal axes; and (4) LEC and medial entorhinal cortex (MEC). Results showed that dual vmThal-LEC/PER-projecting cell populations are found in MS, vSub, and the shallow layers II/III of LEC and MEC. We did not find any dual projecting cells in mPFC or in the cornu ammonis (CA) subfields of the HC. Thus, mPFC and HC activity is sent to vmThal and LEC/PER via non-overlapping projection cell populations. Importantly, the dual projecting cell populations in MS, vSub, and EC are in a unique position to simultaneously influence both cortical and thalamic mPFC-HC pathways critical to memory.Significance StatementThe interactions between mPFC and HC are critical for learning and memory, and dysfunction within this circuit is implicated in various neurodegenerative and psychiatric diseases. mPFC-HC interactions are mediated through multiple communication pathways including a thalamic hub through the vmThal and a cortical hub through lateral entorhinal cortex and perirhinal cortex. Our data highlight newly identified dual projecting cell populations in the septum, Sub, and EC of the rat brain. These dual projecting cells may have the ability to modify the information flow within the mPFC-HC circuit through synchronous activity, and thus offer new cell-specific circuit targets for basic and translational studies in memory.
Analysis of genotype by environment interactions in a maize mapping population
Authors: Hudson Asher I. , Odell Sarah G. , Dubreuil Pierre , Tixier Marie-Helene , Praud Sébastien , Runcie Daniel E. , Ross-Ibarra Jeffrey 
Published: July 2021

AbstractGenotype by environment interactions are a significant challenge for crop breeding as well as being important for understanding the genetic basis of environmental adaptation. In this study, we analyzed genotype by environment interaction in a maize multi-parent advanced generation intercross population grown across five environments. We found that genotype by environment interactions contributed as much as genotypic effects to the variation in some agronomically important traits. In order to understand how genetic correlations between traits change across environments, we estimated the genetic variance-covariance matrix in each environment. Changes in genetic covariances between traits across environments were common, even among traits that show low genotype by environment variance. We also performed a genome-wide association study to identify markers associated with genotype by environment interactions but found only a small number of significantly associated markers, possibly due to the highly polygenic nature of genotype by environment interactions in this population.
Public health interventions in English local authorities: constructing the facts, (re)imagining the future
Authors: Brackley James , Tuck Penelope , Exworthy Mark 
Published: July 2021

PurposeThis paper examines the contested value of healthy life and wellbeing in a context of severe austerity, exploring how the value of “Public Health” is constructed through and with material-discursive practices and accounting representations. It seeks to explore the political and ethical implications of constructing the valuable through a shared consensus over the “facts” when addressing complex, multi-agency problems with long time horizons and outcomes that are not always easily quantifiable.Design/methodology/approachThe theorisation, drawing on science and technology studies (STS) scholars and Karen Barad's (2007) agential realism, opens up the analysis to the performativity of both material and discursive practices in the period following a major re-organisation of activity. The study investigates two case authorities in England and the national regulator through interviews, observations and documentary analysis.FindingsThe paper demonstrates the deeply ethical and political entanglements of accounting representations as objectivity, consensus and collective action are constructed and resisted in practice. It goes on to demonstrate the practical challenges of constructing “alternative accounts” and “intelligent accountabilities” through times of austerity towards a shared sense of public value and suggests austerity measures make such aims both more challenging and all the more essential.Originality/valueFew studies in the accounting literature have explored the full complexity of valuation practices in non-market settings, particularly in a public sector context; this paper, therefore, extends familiar conceptual vocabulary of STS inspired research to further explore how value(s), ethics and identity all play a crucial role in making things valuable.
Demystifying the role of internal dynamics in the path of innovative competitiveness: a serial mediation model of international joint ventures
Authors: Aggarwal Vijita , Kapoor Madhavi 
Published: July 2021

PurposeThe study proposes and evaluates a parsimonious research framework by integrating the major strategic theories related to an international firm's internal dynamics. This research's essence lies in the proposition that organizational competencies, knowledge resources and processes, absorptive capacity and innovativeness form the underlying base for sustainable competitive advantage in this dynamic world.Design/methodology/approachA cross-sectional explanatory research design is adopted. Using the quantitative data obtained from the sample of Indian international joint ventures (IJVs), partial least squares structural equation modeling (PLS-SEM) is deployed to confirm the proposed relationships among the research constructs. Finally, qualitative interviews helped in triangulating the primary survey's results.FindingsA well-established relationship between knowledge transfer and innovation is negated by the Indian IJVs' data, which is delved deeper with cross-industry qualitative analysis. The novel hierarchical model with multiple mediations has nurtured quite exciting results for the business world with some significant theoretical and managerial implications.Research limitations/implicationsThis study has investigated the nexus between multi-dimensional organizational competencies, knowledge transfer, absorptive capacity and venture innovativeness in the context of Indian IJVs. It has emphasized the role of internal dynamics in cross-cultural joint ventures to attain sustainable competitiveness through strategic and technological efficiency.Originality/valueThe study has addressed the specific research gap of under-investigation of dynamic capabilities and sustainable competitiveness in international joint ventures. It has investigated a complex model of multiple mediations, yielding interesting quantitative results with qualitative insights; which is rare to match in literature.
The dark side of teamwork–the relationship between social stressors, social resources and team member well-being in monocultural and multicultural work teams
Authors: Leifels Katrin , Bowen Paul 
Published: July 2021

PurposeThe purpose of this paper is to explore the relationship between cultural diversity in teams and team members' individual well-being. The paper further explores the relationship between social resources, social stressors, team member well-being and the influence of the type of team individuals are working in (mono- vs. multicultural), gender and individualism/collectivism (IC).Design/methodology/approachUsing data collected via an online survey, the authors analyzed 659 responses from individuals working in mono- and multicultural work teams. A theoretical model explaining the influence of social stressors, social resources, and social and demographic variables was proposed and tested using structural equation modeling.FindingsThe results indicate that members of multicultural work teams perceive significantly more social stressors and lower levels of social resources than do members of monocultural teams. Higher levels of social stressors suggest decreased psychological well-being, while social resources have an indirect positive effect on psychological well-being. Furthermore, personal characteristics, namely, individualism and gender, have direct effects on the perception of social stressors and indirect effects on team member well-being.Originality/valueThis paper demonstrates that cultural diversity in teams can influence the social stressors and resources that individual team members experience. Moreover, the pivotal role of social resources in the facilitation of team member well-being is highlighted primarily through its direct effect on social stressors and its concomitant indirect effect on well-being.
Government support for SMEs in response to COVID-19: theoretical model using Wang transform
Authors: Wang Shaun Shuxun , Goh Jing Rong , Sornette Didier , Wang He , Yang Esther Ying 
Published: July 2021

PurposeMany governments are taking measures in support of small and medium-sized enterprises (SMEs) to mitigate the economic impact of the COVID-19 outbreak. This paper presents a theoretical model for evaluating various government measures, including insurance for bank loans, interest rate subsidy, bridge loans and relief of tax burdens.Design/methodology/approachThis paper distinguishes a firm's intrinsic value and book value, where a firm can lose its intrinsic value when it encounters cash-flow crunch. Wang transform is applied to (1) calculating the appropriate level of interest rate subsidy payable to incentivize banks to issue more loans to SMEs and to extend the loan maturity of current debt to the SMEs, (2) describing the frailty distribution for SMEs and (3) defining banks' underwriting capability and overlap index in risk selection.FindingsGovernment support for SMEs can be in the form of an appropriate level of interest rate subsidy payable to incentivize banks to issue more loans to SMEs and to extend the loan maturity of current debt to the SMEs.Research limitations/implicationsMore available data on bank loans would have helped strengthen the empirical studies.Practical implicationsThis paper makes policy recommendations of establishing policy-oriented banks or investment funds dedicated to supporting SMEs, developing risk indices for SMEs to facilitate refined risk underwriting, providing SMEs with long-term tax relief and early-stage equity-type investments.Social implicationsThe model highlights the importance of providing bridge loans to SMEs during the COVID-19 disruption to prevent massive business closures.Originality/valueThis paper provides an analytical framework using Wang transform for analyzing the most effective form of government support for SMEs.
A computational model for diffusion-reaction-deformation coupled problems and its finite element implementation
Authors: Qin Bao , Zhou Yexin , Zhong Zheng 
Published: July 2021

PurposeA diffusion-reaction-deformation coupled model is employed and implemented as a user-defined element (UEL) subroutine in the commercial finite element software package ABAQUS.Design/methodology/approachChemical reaction and diffusion are treated as two distinct processes by introducing the extent of reaction and the diffusion concentration as two kinds of independent variables, for which the independent governing equations for chemical reaction and diffusion processes are obtained. Furthermore, an exponential form of chemical kinetics, instead of the linearly phenomenological relation, between the reaction rate and the chemical affinity is used to describe reaction process. As a result, complex chemical reaction can be simulated, no matter it is around or away from equilibrium.FindingsTwo numerical examples are presented, one for validation of the model and another for the modeling of the deflection of a plane caused by a chemical reaction.Originality/value1. Independent governing equations for diffusion and reaction processes are given. 2. An exponential relation between the reaction rate and its driving force is employed. 3. The UEL subroutine is used to implement the finite element procedure.
Predicting the adoption of mobile payment applications during the COVID-19 pandemic
Authors: Rafdinal Wahyu , Senalasari Widi 
Published: July 2021

PurposeThis study aims to analyse the adoption of mobile payment applications during the coronavirus disease 2019 (COVID-19) pandemic using the technology acceptance model (TAM) and Technology Readiness Index (TRI).Design/methodology/approachThe data were collected from 400 mobile payment application users in Indonesia. The structural equation model–partial least square (SEM-PLS) analysis was conducted to analyse the relationship between variables and test a series of hypotheses.FindingsTRI constructs affect perceived usefulness and perceived ease of use, with the exception of discomfort which has no significant effect on the perceived usefulness. In addition, attitude is influenced by two main TAM variables: perceived usefulness and perceived ease of use. Meanwhile, the intention to use mobile payment applications is influenced by attitude.Research limitations/implicationsThis study will assist mobile payment application service providers and policymakers in planning services and increasing the adoption of mobile payment applications during the COVID-19 pandemic. This study will also add the existing knowledge about the mobile payment applications literature in the context of a pandemic.Originality/valueThis study is the first to empirically employ the TAM and TRI in analysing the adoption of mobile payment applications during the COVID-19 pandemic.