bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ca2+ Mediates HIF-dependent Upregulation of Aquaporin 1 in Pulmonary Arterial Smooth Muscle Cells
Authors: Yun Xin , Maman Stephan , Jiang Haiyang , Semenza Gregg L. , Shimoda Larissa A. 
Published: December 2021

ABSTRACTProlonged exposure to hypoxia causes structural remodeling and sustained contraction of the pulmonary vasculature, resulting in the development of pulmonary hypertension. Both pulmonary arterial smooth muscle cell (PASMC) proliferation and migration contribute to the vascular remodeling. We previously showed that the protein expression of aquaporin 1 (AQP1), a membrane water channel protein, is elevated in PASMCs during following in vivo or in vitro exposure to hypoxia. Studies in other cell types suggest that AQP1 is a direct transcriptional target of hypoxia inducible factor (HIF)-1. Moreover, we and others have shown that an increase in intracellular calcium concentration ([Ca2+]i) is a hallmark of hypoxic exposure in PASMCs. Thus, we wanted to determine whether HIF regulates AQP1 in PASMCs and, if so, whether the process occurred via transcriptional regulation or was Ca2+-dependent. PASMCs were exposed to hypoxia, incubated with DMOG, which inhibits HIFα protein degradation or infected with constitutively active forms of HIF-1α or HIF-2α. Hypoxia, DMOG and HIF1/2α produced a time-dependent increase in AQP1 protein, but not mRNA. Interestingly, incubation with increasing HIF1/2a levels and DMOG increased [Ca2+]i in PASMCs, and this elevation was prevented by the voltage-gated Ca2+ channel inhibitor, verapamil (VER) and nonselective cation channel inhibitor SKF96365 (SKF). VER and SKF also blocked upregulation of AQP1 protein by DMOG or HIF1/2α, but had no effect on expression of GLUT1, a canonical HIF transcriptional target. Silencing of AQP1 abrogated increases in PASMC migration and proliferation induced by HIF1/2α, suggesting induction of AQP1 protein by HIF1/2α has a functional outcome in these cells. Thus, our results show that contrary to reports in other cell types, in PASMCs, AQP1 does not appear to be a direct target for HIF transcriptional regulation. Instead, AQP1 protein may be upregulated by a mechanism involving HIF-dependent increases in [Ca2+]i.
A method to build extended sequence context models of point mutations and indels
Authors: Bethune Jörn , Kleppe April , Besenbacher Søren 
Published: December 2021

AbstractThe mutation rate of a specific position in the human genome depends on the sequence context surrounding it. Modeling the mutation rate by estimating a rate for each possible k-mer, however, only works for small values of k since the data becomes too sparse for larger values of k. Here we propose a new method that solves this problem by grouping similar k-mers using IUPAC patterns. We refer to the method as k-mer pattern partition and have implemented it in a software package called kmerPaPa. We use a large set of human de novo mutations to show that this new method leads to improved prediction of mutation rates and makes it possible to create models using wider sequence contexts than previous studies. Revealing that for some mutation types, the mutation rate of a position is significantly affected by nucleotides that are up to four base pairs away. As the first method of its kind, it does not only predict rates for point mutations but also indels. We have additionally created a software package called Genovo that, given a k-mer pattern partition model, predicts the expected number of synonymous, missense, and other functional mutation types for each gene. Using this software, we show that the created mutation rate models increase the statistical power to detect genes containing disease-causing variants and to identify genes under strong constraint, e.g. haploinsufficient genes.
Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration
Authors: Duncan Emily D. , Han Ke-Jun , Trout Margaret A. , Prekeris Rytis 
Published: December 2021

ABSTRACTCell migration is a complex process that involves coordinated changes in membrane transport, actin cytoskeleton dynamics, and extracellular matrix remodeling. Ras-like small monomeric GTPases, such as Rap2, play a key role in regulating actin cytoskeleton dynamics and cell adhesions. However, how Rap2 function, localization, and activation are regulated during cell migration is not fully understood. We previously identified the small GTPase Rab40b as a regulator of breast cancer cell migration. Rab40b contains a Suppressor of Cytokine Signaling (SOCS) box, which facilitates binding to Cullin5, a known E3 Ubiquitin Ligase component responsible for protein ubiquitylation. In this study, we show that the Rab40b/Cullin5 complex ubiquitylates Rap2. Importantly, we demonstrate that ubiquitylation regulates Rap2 activation, as well as recycling of Rap2 from the endolysosomal compartment to the lamellipodia of migrating breast cancer cells. Based on these data, we propose that Rab40b/Cullin5 ubiquitylates and regulates Rap2-dependent actin dynamics at the leading-edge, a process that is required for breast cancer cell migration and invasion.SUMMARYThe Rab40b/Cul5 complex is an emerging pro-migratory molecular machine. Duncan et al. identify the small GTPase Rap2 as a substrate of the Rab40b/Cul5 complex. They provide evidence that Rab40b/Cul5 ubiquitylates Rap2 to regulate its localization and activity during breast cancer cell migration, ultimately proposing a model by which Rap2 is targeted to the leading-edge plasma membrane to regulate actin dynamics during cell migration.
Covid-19 social distancing: when less is more
Authors: Neuwirth C. , Gruber C. 
Published: December 2021

AbstractCovid-19 is the first digitally documented pandemic in history, presenting a unique opportunity to learn how to best deal with similar crises in the future. In this study we have carried out a model-based evaluation of the effectiveness of social distancing, using Austria and Slovenia as examples. Whereas the majority of comparable studies have postulated a negative relationship between the stringency of social distancing (reduction in social contacts) and the scale of the epidemic, our model has suggested a sinusoidal relationship, with tipping points at which the system changes its predominant regime from ‘less social distancing – more cumulative deaths and infections’ to ‘less social distancing – fewer cumulative deaths and infections’. This relationship was found to persist in scenarios with distinct seasonal variation in transmission and limited national intensive care capabilities. In such situations, relaxing social distancing during low transmission seasons (spring and summer) was found to relieve pressure from high transmission seasons (fall and winter) thus reducing the total number of infections and fatalities. Strategies that take into account this relationship could be particularly beneficial in situations where long-term containment is not feasible.
Sensory nerves enhance triple-negative breast cancer migration and metastasis via the axon guidance molecule PlexinB3
Authors: Le Thanh T , Payne Samantha L , Buckwald Maia N , Hayes Lily A , Burge Christopher B , Oudin Madeleine J 
Published: December 2021

AbstractIn breast cancer, nerve presence has been correlated with more invasive disease and worse prognosis, yet the mechanisms by which different types of peripheral nerves drive tumor progression remain poorly understood. In this study, we identified sensory nerves as more abundant in human triple-negative breast cancer (TNBC) tumors. Coinjection of sensory neurons isolated from the dorsal root ganglia (DRG) of adult female mice with human TNBC cells in immunocompromised mice increased the number of lung metastases. Directin vitroco-culture of human TNBC cells with the dorsal root ganglia (DRG) of adult female mice revealed that TNBC cells adhere to sensory neuron fibers leading to an increase in migration speed. Species-specific RNA sequencing revealed that co-culture of TNBC cells with sensory nerves upregulates the expression of genes associated with cell migration and adhesion in cancer cells. We demonstrate that the axon guidance molecule Plexin B3 mediates cancer cell adhesion to and migration on sensory nerves. Together, our results identify a novel mechanism by which nerves contribute to breast cancer migration and metastasis by inducing a shift in TNBC cell gene expression and support the rationale for disrupting neuron-cancer cell interactions to target metastasis.SignificanceThe presence of nerves in breast tumors has been associated with poor outcome. Understanding the mechanisms by which nerves contribute to tumor progression could help identify novel strategies to target metastatic disease.
Relationship between perceived performance management system (PMS) effectiveness, work engagement and turnover intention: mediation by psychological contract fulfillment
Authors: Sharma Neha Paliwal , Sharma Tanuja , Nanda Agarwal Madhushree 
Published: December 2021

PurposePerformance management systems (PMSs) are critical for organizational success, but research is undecided on their constructive influence and the means through which they impact work engagement and turnover intention. This study aims to fill this gap by surmising psychological contract fulfillment as a mediator in the relationship between PMS effectiveness (PMSE) and employee outcomes.Design/methodology/approachThe study uses a survey research design. Data were collected from 327 working professionals in India. The Statistical Package for Social Science Version 10.0 (SPSS 10.0) and the Analysis of Moments Structure (AMOS) 4.0 were used for data analyses.FindingsThe two-factor construct perceived PMSE was found to explain a larger variance in work engagement and turnover intention than the separate measures for its constituents PMS accuracy (PMSA) and PMS fairness (PMSF). Psychological contract fulfillment and work engagement were found to mediate the relationship between PMSE and turnover intention.Research limitations/implicationsThe study broadens the field of research on PMS in important ways. It demonstrates that the two-factor construct PMSE has a larger influence on employee outcomes in comparison to its constituent individual measures PMSA and PMSF. This is also the first study to suggest that in contrast to PMSF, PMSA explains a higher variance in employee outcomes.Practical implicationsThis study validates the strong relationship between PMSE and key employee outcomes. Besides PMSF, managers can use the findings of this study to focus on the “right things” or accuracy in the PMS context to enhance work engagement and reduce turnover.Social implicationsThe study findings will have value everywhere owing to the diffusion and convergence in the human resource management practices of multinational firms irrespective of their contexts (Ananthram and Nankervis, 2013).Originality/valueEarlier PMS studies have mostly been limited to either its fairness or accuracy and attended unduly to its appraisal element. This study adopts a systems vision of PMS and overcomes earlier drawbacks by investigating the role of both PMSA and PMSF in shaping employee outcomes. This is the first study to empirically confirm that in contrast to PMSF, the PMSA constituent of PMSE explains a higher variance in employee outcomes. The study provides greatly essential pragmatic support to the conjecture that PMSs advance work engagement (Mone and London, 2014; Gruman and Saks, 2011) and lower turnover intention (Kwak and Choi, 2015).
Disclosure of innovation on sustainability report
Authors: Bronzetti Giovanni , Rija Maurizio , Sicoli Graziella , Ippolito Dominga 
Published: December 2021

PurposeThere are several studies on various aspects of the disclosure of companies but there is little research on elements related to the disclosure of innovation in particular. The work aims to fill this important gap by examining to what extent the companies listed on the Italian Stock Exchange, which prepare the sustainability report (non-financial declaration – NFS), disseminate information relating to innovative activities.Design/methodology/approachThe methodology used to achieve the research goal has used multiple linear regression models (OLS), to study the factors that influence disclosure. The data were collected through the content analysis. The sample is made up of 171 companies listed on the Italian stock exchange which prepared a sustainability report for the period of four years 2016–2019 (Sustainability Reports and Integrated Documentation) and which contain information on innovative activity.FindingsThe research confirms a positive relationship between information on innovation and the economic variables of corporate investment. In addition, an important relationship emerges linked to the disclosure of innovative information and the business sector, innovation investments and R&D activity.Research limitations/implicationsThe work suffers from some limitations: the short period of observation subject to analysis, the lack of sustainability report 2020, the extension of the variables taken into consideration for the implementation of the regression models; it is desirable to consider a wider pool of variables in the future in order to implement further specific tests.Practical implicationsOn a practical level, the research suggests the adoption of a framework on the dissemination of innovative activity that allows easy reading of information (regardless of the sector and company size), built starting from the most representative keywords of the activities innovative, to be included in a specific section of the Sustainability Report. This work contributes to filling a cognitive gap connected to the disclosure of the innovative activity. There is much research on disclosure related to business activities, but no specific research regarding the communication of innovation.Originality/valueThe study conducted contributes to fill a gap in the literature related to the disclosure of the innovative activity. The latter is a strategic element for effective and clear communication with stakeholders.
Bankruptcy at family and non-family firms: do they fail differently?
Authors: Mitter Christine , Walcher Michaela , Mayr Stefan , Duller Christine 
Published: December 2021

PurposeFamily firms strive for transgenerational survivability. Thus, bankruptcy is a daunting event. Whether family firms fail for other causes than non-family firms has been scarcely researched and is investigated in this study.Design/methodology/approachThe paper draws on a sample of 459 Austrian bankruptcy cases to examine the effects of the distinct characteristics of family firms on failure causes.FindingsOur results indicate that family firm characteristics impact their failure, as bankruptcy causes differ from non-family firms. While family firms fail less often than non-family firms due to unqualified management and poor business-economic competencies, external bankruptcy causes, in particular bad debt and economic slowdown, are more widespread.Practical implicationsAs our findings suggest that the close social bonds of family firms may become a burden in crisis situations and make them especially prone to external bankruptcy causes, owner-managers should pay more attention to the dependencies, deficiencies and risks that come with their binding social ties. Moreover, they should rely on external advice and appropriate management tools to better recognize and fend off the resulting risks.Originality/valueTo the best of our knowledge, this is the first study that quantitatively examines differences in bankruptcy causes between family and non-family firms.
Improving the robustness of steel frame structures under localised fire conditions
Authors: Suwondo Riza , Cunningham Lee , Gillie Martin , Suangga Made , Hidayat Irpan 
Published: December 2021

PurposeThe robustness of building structures in a fire has recently drawn wide attention. This study presents the progressive collapse analysis of steel frame building structures under localised fire. The main objective of this study is to propose methods to enhance the structural collapse resistance of such structures in fire.Design/methodology/approachA modelling method was developed and validated against both experimental and analytical studies. Then, a series of robustness analyses were performed to investigate the interaction among the members and the pattern of load distribution within the structures. These analyses show that lateral resistance and load redistribution have a vital role in the robustness of the building. Thus, two approaches have been adopted to enhance the robustness of the focused steel frame during a fire.FindingsIt is found that increased size of floor beams and vertical bracing systems are effective measures in preventing whole structure collapse. The larger beam section is able to prevent catenary action so that the load in the failed columns can safely transfer to the adjacent columns without buckling. On the other hand, the bracing system improves the lateral resistance that can accommodate the lateral force when catenary action occurs in the beam.Originality/valuePrevious studies have focused on the collapse mechanism of steel frame structures. However, the parameters affecting the structural robustness in a fire have not yet been explored. To address this gap, this study adopted numerical modelling to undertake parametric studies to identify effective methods to improve the robustness of such structures under fire conditions.
Network topology and patch connectivity affect dynamics in experimental and model metapopulations
Authors: Arancibia Paulina A. , Morin Peter J. 
Published: December 2021

Abstract

Biological populations are rarely isolated in space and instead interact with others via dispersal in metapopulations. Theory predicts that network connectivity patterns can have critical effects on network robustness, as certain topologies, such as scale‐free networks, are more tolerant to disturbances than other patterns. However, at present, experimental evidence of how these topologies affect population dynamics in a metapopulation framework is lacking.

We used experimental metapopulations of the aquatic protist Paramecium tetraurelia to determine how network topology influences occupation patterns.

We created metapopulations engineered to be comparable in linkage density, but differing in their degree distribution. We compared random networks to scale‐free networks by evaluating local population occupancy and abundance throughout 18–30 protist generations. In parallel, we used simulations to explore differences in patch occupation patterns among topologies.

Our experimental results highlighted the importance of the balance between dispersal and extinction in the interaction with spatial network topology. Under low dispersal conditions, random metapopulations of P. tetraurelia reached higher abundance and higher occupancy (proportion of occupied patches) compared to scale‐free systems in both experimental and simulated systems. Under high dispersal conditions, we did not detect differences between types of metapopulations. Increasing patch degree (i.e. number of connections per patch) reduced the probability of extinction of local populations in both types of networks.

We suggest the interaction between colonization/extinction rates and network topology alters the likelihood of rescue effects which results in differential patterns of occupancy and abundance in metapopulations.
Are floral traits good predictors of effective pollinators? A test of pollination syndromes
Authors: de los Santos‐Gómez Samantha Maite , Figueroa‐Castro Dulce María , Castañeda‐Posadas Carlos 
Published: December 2021

AbstractPollination syndromes have been widely used to predict the groups of pollinators of plants. Their predictability has been demonstrated for plant species pollinated by bees, birds, and bats. However, the importance of other aspects on the predictability of pollination syndromes still remain unknown. For instance, plant life cycle has not been considered in evaluations of the pollination syndrome predictability. The goal of this study was to evaluate the predictability of pollination syndromes in nine species with contrasting life cycles. Pollination syndromes were inferred based on floral traits of each plant species, whereas pollinator effectiveness of each group of floral visitors was established through pollen load analysis. Predictability of pollination syndromes was tested through the association between floral traits and the abundance of the most‐effective pollinators. Bees, flies, birds, beetles, and butterflies were the primary and secondary pollinators inferred from floral traits of each species. Although six out of the nine plant species studied were visited by effective pollinators; only four species were effectively pollinated by the groups of primary or secondary pollinators predicted from floral traits. However,Dahlia coccineaandTigridia pavoniawere the only species in which the predicted pollinator group was both effective and showed an association with floral traits. Pollination syndromes were not predictive of pollinators for any of the annual and perennial plant species. Although pollination syndromes are useful to understand some aspects of the reproductive biology of plant species, several other factors might have a role on their predictability.
Alcohol use at the intersection of sexual orientation and gender identity in a representative sample of youth in Colorado
Authors: Gerke Donald R. , Call Jarrod , Atteberry‐Ash Brittanie , Katz‐Kattari Shanna , Kattari Leonardo , Hostetter C. Riley 
Published: December 2021

AbstractBackground and ObjectivesLesbian, gay, bisexual, and questioning (LGBQ) youth are at greater risk of problematic alcohol use than their heterosexual peers, yet there is a dearth of research examining variability in alcohol use among youth that simultaneously accounts for sexual orientation and gender identity. This paper examines the relationship between alcohol use and intersecting identities of sexual orientation and gender while accounting for this population's disproportionate experiences of depression and dating and sexual violence.MethodsThe study used a representative sample (n = 27,621) of high school students. Logistic regressions were used to determine if earlier age at first drink, 30‐day alcohol use, and binge drinking were significantly related to intersectional sexual orientation and gender identity. Secondary models added depression, dating violence, and sexual violence to analyses to determine if they explained any of the variance in alcohol use variables in LGBQ and transgender youth.ResultsTransgender youth who identified as heterosexual or questioning their sexual orientation were at greatest risk for early initiation of alcohol use and binge drinking. These relationships between intersectional identity and alcohol use became nonsignificant when depression, dating violence, and sexual violence were added to the models.Conclusions and Scientific SignificanceThis is the first study to examine relationships between intersecting identities of sexual orientation and gender identity and alcohol use among youth. Risky alcohol use among transgender youth may be attributed to experiences of depression, dating violence, and sexual violence impacting these populations. Interventions should focus on reducing transgender youth exposure to violence.