bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential impact of GABAA receptors and gephyrin post-translational modifications on layer 2/3 pyramidal neuron responsiveness in vivo
Authors: Tsai Yuan-Chen , Hleihil Mohammad , Otomo Kanako , Abegg Andrin , Cavaccini Anna , Panzanelli Patrizia , Cramer Teresa , Ferrari Kim David , Barrett Matthew J.P. , Bosshard Giovanna , Karayannis Theofanis , Weber Bruno , Stobart Jillian L. , Tyagarajan Shiva K.
Published: November 2020

A diverse set of GABAA receptors (GABAARs) enable synaptic plasticity adaptations at inhibitory postsynaptic sites in collaboration with the scaffolding protein gephyrin. Early studies helped to identify distinctions between GABAAR subtypes allocated within specific functional circuits, but their contribution to the changing dynamics of a microcircuit remains unclear. Here, using the whisker-barrel system in mouse, we assessed the contribution of specific synaptic GABAAR subtypes and gephyrin scaffolding changes to sensory processing in vivo. We monitored spontaneous and evoked Ca2+ transients in layer 2/3 pyramidal cells with the genetically encoded Ca2+ sensor RCaMP1.07. Using Gabra1 or Gabra2 global and conditional knockout mice, we uncovered that α1- and α2-GABAARs determine the sparseness of L2/3 pyramidal neuron encoding. In a cell-type dependent manner, α1-GABAARs and α2-GABAARs affected neuronal excitability and the reliability of neuronal responses after whisker stimulation. We also discerned that gephyrin with its diverse post-translational modifications (PTMs) shows preference for specific GABAAR subtype to facilitate microcircuit activity. Our results underscore the relevance of the diversity of GABAARs within a cortical microcircuit.

Key points

While GABAergic inhibition from interneuron subtypes regulates cortical microcircuit activity the molecular determinants have remain unclear.

We demonstrate that specific-GABAA receptor subtypes contribute differentially to layer 2/3 neuronal activities in mouse barrel cortex.

Importantly, we link the GABAAR contributions to the scaffolding properties of its important postsynaptic density protein gephyrin. We show that different PTMs on gephyrin determines neuronal excitability via GABAAR recruitment and modulation of inhibition within layer 2/3 neurons.

Specifically, α1 and α2 subunits containing GABAA receptors, along with their scaffolding protein gephyrin determine the distribution of high, medium and low activity pyramidal neurons during sensory encoding, whereby controlling the total activity of cortical microcircuit.
The C99 domain of the amyloid precursor protein is a disordered membrane phase-preferring protein
Authors: Capone Ricardo , Tiwari Ajit , Hadziselimovic Arina , Peskova Yelena , Hutchison James M. , Sanders Charles R. , Kenworthy Anne K.
Published: November 2020

Processing of the amyloid precursor protein (APP) via the amyloidogenic pathway is associated with the etiology of Alzheimer’s disease. The cleavage of APP by β-secretase to generate the transmembrane 99-residue C-terminal fragment (C99) and subsequent processing of C99 by γ-secretase to yield amyloid-β (Aβ) peptides are essential steps in this pathway. Biochemical evidence suggests amyloidogenic processing of C99 occurs in cholesterol- and sphingolipid-enriched liquid ordered phase membrane raft domains. However, direct evidence that C99 preferentially associates with rafts has remained elusive. Here, we test this idea by quantifying the affinity of C99-GFP for raft domains in cell-derived giant plasma membrane vesicles. We find that C99 is essentially excluded from ordered domains in HeLa cells, SH-SY5Y cells and neurons, instead exhibiting a strong (roughly 90%) affinity for disordered domains. The strong association of C99 with disordered domains occurs independently of its cholesterol binding activity, homodimerization, or the familial Alzheimer disease Arctic mutation. Finally, we confirm previous studies suggesting that C99 is processed in the plasma membrane by α-secretase, in addition to the well-known γ-secretase. These findings suggest that C99 itself lacks an intrinsic affinity for raft domains, implying either that amyloidogenic processing of the protein occurs in disordered regions of the membrane, that processing involves a marginal sub-population of C99 found in rafts, or that as-yet-unidentified protein-protein interactions involving C99 in living cells drive it into rafts to promote its cleavage therein.
Global analysis of protein-RNA interactions in SARS-CoV-2 infected cells reveals key regulators of infection
Authors: Kamel Wael , Noerenberg Marko , Cerikan Berati , Chen Honglin , Järvelin Aino I. , Kammoun Mohamed , Lee Jeff , Shuai Ni , Garcia-Moreno Manuel , Andrejeva Anna , Deery Michael J. , Neufeldt Christopher J. , Cortese Mirko , Knight Michael L. , Lilley Kathryn S. , Martinez Javier , Davis Ilan , Bartenschlager Ralf , Mohammed Shabaz , Castello Alfredo
Published: November 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. SARS-CoV-2 relies on cellular RNA-binding proteins (RBPs) to replicate and spread, although which RBPs control SARS-CoV-2 infection remains largely unknown. Here, we employ a multi-omic approach to identify systematically and comprehensively which cellular and viral RBPs are involved in SARS-CoV-2 infection. We reveal that the cellular RNA-bound proteome is remodelled upon SARS-CoV-2 infection, having widespread effects on RNA metabolic pathways, non-canonical RBPs and antiviral factors. Moreover, we apply a new method to identify the proteins that directly interact with viral RNA, uncovering dozens of cellular RBPs and six viral proteins. Amongst them, several components of the tRNA ligase complex, which we show regulate SARS-CoV-2 infection. Furthermore, we discover that available drugs targeting host RBPs that interact with SARS-CoV-2 RNA inhibit infection. Collectively, our results uncover a new universe of host-virus interactions with potential for new antiviral therapies against COVID-19.
Different contrast encoding in ON and OFF visual pathways
Authors: Idrees Saad , Münch Thomas A.
Published: November 2020

Subjective visual experience builds on sensory encoding of light reflected by different objects in our environment. Most retinal ganglion cells encode changes in light intensity, quantified as contrast, rather than the absolute intensity. Mathematically, contrast is often defined as a relative change in light intensity. Activity in the visual system and perceptual responses are usually explained with such definitions of contrast. Here, for the first time, we explicitly explored how contrast is actually represented in the visual system. Using mouse retina electrophysiology, we show that response strength of OFF retinal ganglion cells does not represent relative, but absolute changes in light intensity. ON RGC response strength is governed by a combination of absolute and relative change in light intensity. This is true for a wide range of ambient light levels, at least from scotopic to high mesopic regimes. Consequently, light decrements and increments are represented asymmetrically in the retina, which may explain the asymmetries in responses to negative and positive contrast observed throughout the visual system. These findings may help to more thoroughly design and interpret vision science studies where responses are driven by contrast of the visual stimuli.
Modeling Research Project Grant Success Rates from NIH Appropriation History: Extension to 2020
Authors: Berg Jeremy M.
Published: November 2020

Communication of the likelihood that a grant proposal is funded is important for individual researchers and academic institutions. For research project grants (RPGs) funded by the US National Institutes of Health (NIH), this is measured by the success rate, the fraction of grants reviewed in a given fiscal year that are funded. In 2016, I posted a relatively simple computational model that allowed estimation of these success rates from historical data of NIH appropriations and associated data, based largely on the fact that commitments to fund NIH grants are typically made over four fiscal years rather than coming from a single fiscal year’s appropriations. Data for appropriations and success rates for fiscal years 2016-2020 are now available, allowing this model to be tested without no adjustable parameters. Over this period, the NIH appropriation increased by 29.7% to $39.313 billion, yet the RPG success rate increased from 0.183 to 0.201, a relative increase of only 9.8%. This difference is accurately reproduced by the model, indicating that the modest changes in success rate despite large appropriation increases reflect the consequences of the funding grants from multiple fiscal years and the response of the biomedical research community in submitting an increased number of proposals. The model can also be extended to estimate the success rates for individual institutes with reasonable accuracy.
Separation and Characterization of Endogenous Nucleosomes by Native Capillary Zone Electrophoresis – Top-Down Mass Spectrometry (nCZE-TDMS)
Authors: Jooß Kevin , Schachner Luis F. , Watson Rachel , Gillespie Zachary B. , Howard Sarah A. , Cheek Marcus A. , Meiners Matthew J. , Licht Jonathan D. , Keogh Michael-Christopher , Kelleher Neil L.
Published: November 2020

We report a novel platform (native capillary zone electrophoresis – top-down mass spectrometry; nCZE-TDMS) for the separation and characterization of whole nucleosomes, their histone subunits, and PTMs. As the repeating unit of chromatin, mononucleosomes (Nucs) are a ~200 kDa complex of DNA and histone proteins involved in the regulation of key cellular processes central to human health and disease. Unraveling the covalent modification landscape of histones and their defined stoichiometries within Nucs helps to explain epigenetic regulatory mechanisms. In nCZE-TDMS, online Nuc separation is followed by a three-tier tandem MS approach that measures the intact mass of Nucs, ejects and detects the constituent histones, and fragments to sequence the histone. The new platform was optimized with synthetic Nucs to reduce both sample requirements and cost significantly compared to direct infusion. Limits of detection were in the low attomole range, with linearity over ~three orders of magnitude. The nCZE-TDMS platform was applied to endogenous Nucs from two cell lines distinguished by overexpression or knockout of histone methyltransferase NSD2/MMSET, where analysis of constituent histones revealed changes in histone abundances over the course of the CZE separation. We are confident the nCZE-TDMS platform will help advance nucleosome-level research in the fields of chromatin and epigenetics.
An evaluation of multi-excitation-wavelength standing-wave fluorescence microscopy (TartanSW) to improve sampling density in studies of the cell membrane and cytoskeleton
Authors: Schniete Jana K. , Tinning Peter W. , Scrimgeour Ross C. , Robb Gillian , Kölln Lisa S. , Wesencraft Katrina , Paul Nikki R. , Bushell Trevor J. , McConnell Gail
Published: November 2020

Conventional standing-wave (SW) fluorescence microscopy uses a single wavelength to excite fluorescence from the specimen, which is normally placed in contact with a first surface reflector. The resulting excitation SW creates a pattern of illumination with anti-nodal maxima at multiple evenly-spaced planes perpendicular to the optical axis of the microscope. These maxima are approximately 90 nm thick and spaced 180 nm apart. Where the planes intersect fluorescent structures, emission occurs, but between the planes are non-illuminated regions which are not sampled for fluorescence. We evaluate a multi-excitation-wavelength SW fluorescence microscopy (which we call TartanSW) as a method for increasing the density of sampling by using SWs with different axial periodicities, to resolve more of the overall cell structure. The TartanSW method increased the sampling density from 50% to 98% over seven anti-nodal planes, with no notable change in axial or lateral resolution compared to single-excitation-wavelength SW microscopy. We demonstrate the method with images of the membrane and cytoskeleton of living and fixed cells.
Attitudes towards risk and decision-making within local government
Authors: Grimley Mairead , Burnard Kevin John
Published: November 2020

Purpose

This case study aims to explore the perceptions and attitudes towards risk within a UK local authority and the subsequent effects on decision-making. Through a qualitative analysis of both primary and secondary data, this study advances current understanding of the complex relationships between risk and decision-making. The study concludes by suggesting how local governments may better provide value to constituents.

Design/methodology/approach

This research follows a single case study approach. Data were collected through both a focused online survey and semi-structured interviews. Respondents were selected through purposive sampling in order to capture direct insights and understanding of the concepts under consideration. The study focuses on a single local authority within the UK.

Findings

Building on extant literature, this case study highlights both the individual and organisational considerations towards risk perception. Following the analysis of collected data, the study highlights the influence of risk aversion and public involvement within decision-making.

Originality/value

By aiming to improve and advance understanding of risk and decision-making in a local authority setting, the relevance of this research may be wider than internal organisational structures. The study provides recommendations for further research towards facilitating the inclusion of the citizen within decision-making processes.
Nitrous oxide use among young people – new trends, policy challenges, and knowledge gaps
Authors: Asmussen Frank Vibeke , MacLean Sarah , Herold Maria Dich
Published: November 2020

Purpose

Nitrous oxide (N2O) use for recreational purposes appears to have increased among young people in several countries, including Denmark, Australia, The Netherlands and the UK. This increase has prompted concern among health authorities and politicians. The purpose of this paper is to map out findings in the available literature about N2O use among young people to better understand current trends and contextualize the public concerns and the new policy responses to it.

Design/methodology/approach

The authors draw here on a range of sources, including research literature, reports and policy documents in English and Danish. Given the broad aim, the authors used a scoping study approach (Arksey and O’Malley, 2005).

Findings

The authors found literature on prevalence of use, health effects and policy regulations. The literature suggests that health harms associated with N2O use are generally associated with intensive and long-term use, and death is more likely where the means of administration entails a risk of suffocation. Overall, however, the analysis shows that substantial gaps exist in the available literature. The authors lack detailed knowledge on several issues, including comparable prevalence data of N2O use; the extent to which N2O is used with other drugs; how one can distinguish between harmful and non-harmful use in terms of both quantity inhaled and mode of administration; and on intended and unintended consequences of policy responses to this use.

Originality/value

The current increase and trend in inhaling N2O for intoxication among young people is under researched. This general review maps out what kind of knowledge would be valuable to have for prevention, harm reduction and policy interventions.
Resource transformation in the reconstitution of broken interorganizational relationships
Authors: Poblete León
Published: November 2020

Purpose

Adopting aspects of the resource-based perspective and interorganizational relational dynamics, this paper examines the notion of resource transformation in the reconstitution of broken interorganizational relationships.

Design/methodology/approach

Following a qualitative approach, the research involved four in-depth case studies of buyer–supplier relationships among 12 Scandinavian manufacturing firms.

Findings

The results suggest that reconstituting broken interorganizational relationships, whether overlooked or underutilized, can pose important consequences for resource transformations. To adapt in dynamic environments, firms use resources in new combinations, and various relationship-specific resources may be difficult, if not impossible, to transform independent of the reconstitution process. Such resource transformations can occur when competencies in reconstituting interorganizational relationships are combined to synthesize novel resources or recombined with other resources. Four identified types of resource transformations in reconstitution processes – in production facilities, products, human know-how and coordination of interorganizational collaboration – can occur in each firm and/or in the interorganizational relationship.

Research limitations/implications

Although the explorative multiple-case study approach afforded novel insights, the findings have no representative or generalizable implications in any positivist sense and thus warrant careful interpretation. Nevertheless, they make important contributions to the literature and illuminate promising avenues for future research, which should involve additional data collection and quantitative studies.

Practical implications

As firms reconstitute broken interorganizational relationships, the transformation of their resources can provide new, expected resources capable of generating substantial benefits.

Originality/value

This paper fills an identified gap in research regarding how reconstituting broken interorganizational relationships influence the transformation of resources. The paper provides new conceptual and empirical insights as well as makes several contributions to the literature on the topic.
HR’s ever-emerging contribution
Authors: Ulrich Dave
Published: November 2020

Purpose

This paper aims to examine the future contribution of human resources (HR) in three areas: first, the evolution of four waves of HR value creation leading to an outside-in focus. Second, HR insights about individual competence (talent), leadership and organization capabilities (culture). Third, creating more effective HR departments and upgrading HR professionals.

Design/methodology/approach

The author, Dave Ulrich, has worked extensively on HR theory, research and practice. This paper synthesizes and extends his (and others’) thinking about HR’s evolving contributions.

Findings

HR is not about HR, but about helping an organization succeed in the marketplace through talent, leadership and organization. HR departments can be assessed and improved based on nine dimensions and HR professionals can recognize and master competencies that help them deliver value.

Originality/value

Reading should come away recognize where HR can continue to contribute to individual and organizational success through thinking outside in, delivering HR agenda (talent, leadership and organization), and improving the HR department and upgrading HR professionals.
Does the Combination Matter? Examining the Influence of Alcohol and Cannabis Product Combinations on Simultaneous Use and Consequences in Daily Life
Authors: Stevens Angela K. , Aston Elizabeth R. , Gunn Rachel L. , Sokolovsky Alexander W. , Treloar Padovano Hayley , White Helene R. , Jackson Kristina M.
Published: November 2020

Background

Alcohol and marijuana/cannabis are frequently used simultaneously (i.e., SAM use). SAM use is complex, and the ways in which alcohol and cannabis are simultaneously used may reveal differential effects. The purpose of this study was to examine day‐level effects of distinct alcohol and cannabis product combinations on simultaneous use and consequences on that day.

Methods

College student SAM users (N = 274; 50% women; Mage = 19.82 years) were recruited to complete 54 days of data collection, including 5 repeated daily surveys each day. We identified 12 distinct product combinations reported during SAM‐use days. We tested 4 reference groups, with one reflecting the most common use pattern and 3 potentially risky use patterns. We considered 3 outcomes (negative consequences, number of drinks, and number of cannabis uses) and used generalized linear mixed‐effects models disentangling within‐ from between‐person effects in all analyses.

Results

Using multiple products (≥2) of alcohol was consistently linked to higher odds of experiencing a negative consequence. Combining beer with only one cannabis product (leaf or concentrate) was consistently associated with lower odds of a consequence. Combining cannabis with multiple alcohol products was associated with heavier alcohol consumption. Using dual cannabis products also was associated with heavier cannabis consumption, but this pattern was not significantly different than using concentrate only on a given day.

Conclusion

This is the first study to examine day‐level influences of distinct alcohol and cannabis product combinations on consumption and consequences among young adult SAM users. Findings suggest that mixing alcohol products confers greater risk for negative consequences and heavier consumption, whereas there is little difference in cannabis consumption when using concentrate only vs. 2 cannabis products on a given day, except for concentrate + beer. Our findings support existing protective strategies of not mixing alcohol products and avoiding use of cannabis concentrate for SAM use as well.
“Dancing on the Brink of the World”: Seeing Indigenous Dance and Resilience in the Archaeology of Colonial California
Authors: Schneider Tsim D.
Published: November 2020

In California, Indigenous hinterlands served as places of opportunity and safe harbor for Native people responding to colonization during the Mission Period (1769–1830s) and afterward. Even as Native communities visited Spanish missions in the San Francisco Bay Area, their long‐standing traditions of mobility supported novel opportunities to depart missions and seek out seasonally available foods. Hinterlands also provided contexts for Native people to conduct other social practices threatened by missionary colonialism. These were places to meet, mourn, dine, and dance. Expanding the Indigenous hinterlands concept, this article addresses the persistence of Indigenous dances. After reviewing the historical record of Native dances in California—simultaneously permitted/documented and forbidden/ignored within mission settings—I examine the archaeology of dances. Evidentiary priorities in archaeology and limited exploration of hinterland settings have impaired the study of where and how colonized people practiced their cultures. By paying closer attention to dance practice and the epistemological gaps in archaeology, Indigenous communities and archaeologists might further enhance studies of postcontact resilience and change and move closer to a decolonized archaeology. [dance, archaeology, colonialism, Indigenous peoples, California]
Higher content of microcystin‐leucine‐arginine promotes the survival of intrahepatic cholangiocarcinoma cells via regulating SET resulting in the poorer prognosis of patients
Authors: Gu Shen , He Wei , Yan Minghao , He Jian , Zhou Qun , Yan Xiaopeng , Fu Xiao , Chen Jun , Han Xiaodong , Qiu Yudong
Published: November 2020

Background & Aims

Intrahepatic cholangiocarcinoma (ICC) has over the last 10 years become the focus of increasing concern largely due to its rising incidence and high mortality rates worldwide. Microcystin‐leucine‐arginine (MC‐LR) has been reported to be carcinogenic, but there are no data on the linkage between MC‐LR and ICC. This study aimed to explore whether the content levels of MC‐LR in the tumour tissues of ICC patients be associated with the prognosis and if so, to characterize the mechanism in ICC cells.

Methods

We conducted a retrospective study to evaluate the prognostic value of MC‐LR in ICC after resection. All patients were divided into two groups according to the content of MC‐LR in tumour via immunohistochemistry: low‐MC‐LR group (n = 28) and high‐MC‐LR group (n = 30).

Results

Multivariate analysis showed high‐MC‐LR level was the prognostic factor for OS and RFS after hepatectomy (P = .011 and .044). We demonstrated that MC‐LR could promote the survival of human ICC cell lines and SET was identified as an important mRNA in the progression via RNA array.

Conclusions

We provide evidence that MC‐LR was an independent prognostic factor for ICC in humans by modulating the expression of SET in human ICC cells.
Adaptive Ad Network Selection for Publisher‐Return Optimization in Mobile‐App Advertising
Authors: Adikari Shalinda , Dutta Kaushik
Published: November 2020

In the era of online advertising, the new norm of mobile‐app advertising defines a novel revenue generation channel for publishers through user‐ and context‐targeted advertisements. Unlike online advertising, mobile‐app advertising has unique behaviors due to certain constraints and attributes. As a result, the existing solutions of return optimization for publishers do not always provide the expected outcome. This has created a new research gap. Finding a solution at the app instance level of the mobile advertising ecosystem has a high potential to bridge this gap. This study provides a full‐fledged mechanism to determine the ad network, which gains the highest return to the publisher at the app instance level based on the attributes of both the advertisement and the ad network. Using such attributes and the mobile‐app user's click behavior, we estimate the ad network effectiveness, the advertisement effectiveness, and the click‐through rate to determine the optimal ad network, which provides the highest return for the publisher. Through a simulation experiment based on data generated in real‐life scenarios, we demonstrate that the publisher‐return is higher in our proposed approach than that obtained from advertisements from a single ad network for all the mobile‐app users.
Extra‐nasal approach to access the dorsal and ventral conchal bullae in horses
Authors: Pouyet M. , Bonilla A.G.
Published: November 2020

Nasal conchal bulla empyema can be found in up to 20% of horses with paranasal sinus disease but remains difficult to diagnose and can result in persistent unilateral discharge before presentation. Our aim in this experimental ex vivo study was to describe two extra‐nasal approaches to access the nasal conchal bullae. Six cadaveric heads were used to determine the ideal landmarks to access the dorsal and ventral conchal bullae through two rhinocenteses performed with the aid of a 14G needle and a mallet through the maxillary bone, and to access both bullae simultaneously through a 13‐mm diameter trephination. Both techniques were performed bilaterally. To assess correct placement of the rhinocenteses and trephination, each bulla was injected with a coloured insulating foam before performing a maxillary bone flap to inspect the bullae. Both bullae were successfully entered with the 14G needle in all instances. The nasolacrimal duct was damaged while entering the ventral conchal bulla in 3/12 approaches. Trephination of the maxillary bone allowed access to both nasal conchal bullae in all cases but one, where the portal was placed too dorsally and did not allow access to the ventral conchal bulla. The opening created with the trephine could allow the use of a small instrument such as a rongeur which could have diagnostic and therapeutic benefits. The limitations are that this was an ex vivo study and nasolacrimal duct damage could have clinical repercussions if the duct becomes obstructed after accessing the ventral conchal bulla. It was concluded that the techniques described are simple, minimally invasive and provide access to the conchal bullae for diagnostic and therapeutic purposes. Additionally, they may reduce the need for CT or laser for the diagnosis and treatment of bulla empyema.
Century‐long records reveal shifting challenges to seagrass recovery
Authors: Krause‐Jensen Dorte , Duarte Carlos M. , Sand‐Jensen Kaj , Carstensen Jacob
Published: November 2020

Global losses over the 20th century placed seagrass ecosystems among the most threatened ecosystems in the world, with eutrophication, and associated deterioration of the submarine light environment identified as the main driver. Growing appreciation of the ecological and societal benefits of healthy seagrass meadows has stimulated efforts to protect and restore them, largely focused on reducing nutrient input to coastal waters. Here we analyze a unique data set spanning 135 years on eelgrass (Zostera marina), the dominant seagrass of the northern hemisphere. We show that meadows in the Western Baltic Sea exhibited major declines relative to historic (1890–1910) reference due to the wasting disease in the 1930s followed by eutrophication peaking in the 1980s, but have only shown modest improvement despite major eutrophication mitigation, halving nitrogen input since the 1980s. Across the past century, we identified generally shallower colonization depths of eelgrass for a given submarine light penetration and, hence, increased apparent light requirements. This suggests that eelgrass recovery is limited by additional stressors. Our study indicates that bottom trawling and intense recent warming (0.5°C per decade, 1985–2018), which impact on deeper and shallower meadows, respectively, suppress eelgrass from fully recovering from eutrophication. Warming is most severe in shallow turbid waters, while clear‐water areas offer eelgrass refugia from warming in deeper, cooler waters; but trawling can prevent eelgrass from reaching these refugia. Efforts to reduce nutrient input and thereby improve water clarity have been instrumental in avoiding a catastrophic loss of eelgrass ecosystems. However, local‐scale future management must, in addition, reduce bottom trawling to facilitate eelgrass reaching deeper, cooler refugia, and increase resilience toward realized and further warming. Warming needs to be limited by meeting global climate change mitigation goals.
Niche dynamics in amphitropical desert disjunct plants: Seeking for ecological and species‐specific influences
Authors: Quiroga R. Emiliano , Premoli Andrea C. , Fernández Roberto J.
Published: November 2020

Aim

Numerous studies have assessed whether species niches are conserved in geographically separated regions. However, most of them were performed on invasive species, with the limitation that such species have likely not yet reached their potential distribution in the invaded region. Here we test the hypothesis of niche conservatism in the entire group of 25 amphitropical desert disjunct plant species, naturally distributed in North and South America but absent in the tropics. We also assessed the influence of ecological (intensity of biotic interactions) and species‐specific factors (dispersal ability and adaptation to stress) on species niche differentiation between the two continents.

Location

North America and South America.

Time period

Recent.

Major taxa studied

Plants. Amphitropical desert disjunct species.

Methods

Species’ presence coordinates and five biologically relevant climatic variables were used to quantify niche differentiation of species between continents by means of principal component analysis. Then, structural equation modelling was performed to assess the influence on niche differentiation of proxies for intensity of biotic interactions (habitat net primary productivity), species dispersibility (dispersal mode and plant traits), and adaptation to stress (leaf size).

Results

Niche shift was detected for 24 out of the 25 species, mostly towards cooler environments in South America (−2.5 °C average) with respect to North America. These niche shifts were best explained by the productivity of species’ habitats, in particular by the displacement of species’ niches away from the more productive and competitive environments of South America.

Main conclusions

Niche shift seems to be the rule in amphitropical desert plants. Our findings highlight a previously undetected connection between amphitropical disjunct species and macroecological characteristics of the Americas. We show that prevalent environments differ between South and North America, and suggest that associated biotic contexts (mainly competition from widespread tropical and subtropical forests in South America) play a determinant role on species’ distribution and niches.
Met and unmet care needs of home‐living people with dementia in China: An observational study using the Camberwell Assessment of Need for the Elderly
Authors: Zhang Juxia , Xu Xiaoqing , Yang LiMei , Wang Jiancheng
Published: November 2020

Aim

The goal of the study was to investigate the patterns of needs in older individuals with mild‐to‐moderate dementia living at home using the Camberwell Assessment of Need for the Elderly questionnaire.

Methods

This was a cross‐sectional study. A total of 378 home‐living residents served as the sample. The Camberwell Assessment of Need for the Elderly questionnaire was used to analyze the needs of those receiving adequate interventions (met needs) and those without appropriate supports (unmet needs). Thereafter, the factors that correlated with total needs were determined using demographic characteristics.

Results

Persons with dementia (PWD) had a mean care needs of 18.5 ± 5.4 (range 5–35). Unmet needs were most common in caring for someone (65.1%), looking after the home (63.5%), self‐care (58.7%) and intimate relationships (44.4%) domains. Higher needs were significantly related to living with others than a spouse, longer length of diagnosis, older age and higher cognitive function.

Conclusion

Unmet needs are common in home‐living PWD. Home‐based dementia care can identify and address PWD's unmet needs by focusing on care recipients and caregivers to enable PWD to remain safely at home and improve their quality of life. Geriatr Gerontol Int 2021; 21: 102–107.
Analyzing the distribution of researchers in China: An approach using multiscale geographically weighted regression
Authors: Gu Hengyu , Yu Hanchen , Sachdeva Mehak , Liu Ye
Published: November 2020

We employ a Multiscale Geographically Weighted Regression (MGWR) model to examine the spatial variation of researchers in China in 2015 and its determinants. It is found that the distribution of researchers is driven by the economy in urban centers, public services, natural areas of recreation, urban consumption, and work‐related facilities. Results from the MGWR model conclusively identify significant spatial non‐stationarity in the determinants measuring scientific researchers' distribution. Other factors such as per capita GDP, the number of hospital beds per 10,000 inhabitants, and public financial expenditures influence the distribution of researchers more in the Western cities, and their effect decreases steadily from West to East. Air pollutants affect researchers negatively in the eastern part of the country, while the percentage of available green land is a strong driver in the central and western parts. The factor measuring the effect of the number of universities is seen to affect researchers more strongly in the northwestern and northeastern cities. Other findings further suggest that the economy and public services in cities have a consistent effect on the distribution of researchers across the country whereas, natural areas of recreation, work‐related facilities, and urban consumption have a significantly varying effect across cities.
Tax enforcement interactions among Chinese provinces: A frontier and spatial analysis
Authors: Chen Longjin
Published: November 2020

Spatial interactions in tax policy have been examined intensively for developed countries. This study presents new evidence of tax enforcement interactions from a developing country. A trend of intensified enforcement on the corporate income tax (CIT) over time is identified among Chinese provinces. Additionally, stringent CIT enforcement in neighboring provinces enhances CIT enforcement in the surrounded province. Furthermore, tax enforcement interactions involve both the state and local tax authorities. The findings not only help to understand the Chinese “regionally decentralized authoritarian system,” but also echo second‐generation fiscal federalism that highlights the role of institutional incentives in shaping intergovernmental fiscal relations.
Impact of antiviral therapy on risk prediction model for hepatocellular carcinoma development in patients with chronic hepatitis B
Authors: Chon Hye Yeon , Lee Jae Seung , Lee Hye Won , Chun Ho Soo , Kim Beom Kyung , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Kim Seung Up
Published: November 2020

Aim

Risk prediction models for hepatocellular carcinoma (HCC) development are available. However, the influence of antiviral therapy (AVT) on these models in patients with chronic hepatitis B is unknown.

Methods

The dynamic changes in risk prediction models during AVT and the association between risk prediction model and the risk of chronic hepatitis B‐related HCC development were investigated. Between 2005 and 2017, 4917 patients with chronic hepatitis B (3361 noncirrhotic, 1556 cirrhotic) were recruited.

Results

The mean age of the study population was 49.3 years and 60.6% (n = 2980) of the patients were male. The mean Chinese University‐HCC (CU‐HCC) score was 12.7 at baseline in the overall study population, and decreased significantly (mean, 8.7) after 1 year of AVT (p < 0.001). The score was maintained throughout 5 years of AVT (mean, 8.4–8.8; p > 0.05). The proportion of high‐risk patients (CU‐HCC score ≥ 20) was 28.9% at baseline, and decreased significantly after 1 year of AVT (5.0%; p < 0.001), and remained stable through 5 years of AVT (2.2%–3.6%; p > 0.05). In addition to the score at baseline, the CU‐HCC score at 1 year of AVT independently predicted the risk of HCC development (hazard ratio = 1.072; p < 0.001), together with male gender and platelet count (all p < 0.05).

Conclusions

The CU‐HCC score significantly decreased at 1 year of AVT and was maintained thereafter. The CU‐HCC score after 1 year of AVT independently predicted the risk of HCC development in patients with chronic hepatitis B.
Double Empirical Bayes Testing
Authors: Tansey Wesley , Wang Yixin , Rabadan Raul , Blei David
Published: November 2020

Analysing data from large‐scale, multiexperiment studies requires scientists to both analyse each experiment and to assess the results as a whole. In this article, we develop double empirical Bayes testing (DEBT), an empirical Bayes method for analysing multiexperiment studies when many covariates are gathered per experiment. DEBT is a two‐stage method: in the first stage, it reports which experiments yielded significant outcomes and in the second stage, it hypothesises which covariates drive the experimental significance. In both of its stages, DEBT builds on the work of Efron, who laid out an elegant empirical Bayes approach to testing. DEBT enhances this framework by learning a series of black box predictive models to boost power and control the false discovery rate. In Stage 1, it uses a deep neural network prior to report which experiments yielded significant outcomes. In Stage 2, it uses an empirical Bayes version of the knockoff filter to select covariates that have significant predictive power of Stage 1 significance. In both simulated and real data, DEBT increases the proportion of discovered significant outcomes and selects more features when signals are weak. In a real study of cancer cell lines, DEBT selects a robust set of biologically plausible genomic drivers of drug sensitivity and resistance in cancer.
Anti–coronavirus disease 2019 (COVID‐19) targets and mechanisms of puerarin
Authors: Qin Xingyue , Huang Chen , Wu Ka , Li Yu , Liang Xiao , Su Min , Li Rong
Published: November 2020

The present study aimed to uncover the pharmacological function and underlying mechanism of puerarin as a potential treatment for COVID‐19, using an in silico methodology, including network pharmacology and molecular docking. The pivotal targets of puerarin to treat COVID‐19 were identified and included the epidermal growth factor receptor (EGFR), tumour necrosis factor (TNF), tumour protein p53 (TP53), caspase 3 (CASP3), RELA proto‐oncogene (RELA), Fos proto‐oncogene (FOS), caspase 8 (CASP8), prostaglandin‐endoperoxide synthase 2 (PTGS2), interleukin 2 (IL2), protein kinase CB (PRKCB), B cell lymphoma/leukaemia gene‐2 (BCL2), protein kinase CA (PRKCA), nitric oxide synthase 3 (NOS3) and peroxisome proliferator–activated receptor gamma (PPARG). Functionally, the anti–COVID‐19 action of puerarin was associated with the suppression of oxidative stress and inflammatory cascades, and cell apoptosis. The signalling pathways of puerarin to treat COVID‐19 included modulation of the pathways of apoptosis, IL‐17 signalling, mitogen‐activated protein kinase (MAPK) signalling and TNF signalling. Molecular docking data illustrated the binding capacity of puerarin with COVID‐19 and the effective anti–COVID‐19 activity of puerarin. Taken together, our current network pharmacology–based findings revealed the pharmacological role of puerarin in the treatment of COVID‐19. Furthermore, the bioinformatic findings elucidated that some of these pivotal targets might serve as potential molecular markers for detecting COVID‐19.
Parenting in Postdivorce Families: The Influence of Residence, Repartnering, and Gender
Authors: Koster Tara , Poortman Anne‐Rigt , van der Lippe Tanja , Kleingeld Pauline
Published: November 2020

Objective

This study investigates the role of residence (including shared residence), repartnering (including LAT relationships), and additional children (step‐ and half‐siblings) on parenting in postdivorce families, and whether patterns differ by gender and type of parenting behavior.

Background

Patterns of parenting are indicative of how parents redefine their roles and responsibilities after divorce and repartnering, but extant research has largely overlooked parenting across a full array of postdivorce families.

Method

The analyses were based on data from Wave 2 of the New Families in the Netherlands survey, which was conducted among a random sample of divorced or separated heterosexual parents with minor children (N = 2,778).

Results

Residence was highly relevant for parenting in regular care, leisure, irregular care, and influence in child‐related decision‐making. Repartnering and additional children had smaller effects and it mattered which type of parenting behavior was considered, but they were generally associated with lower parental engagement, except for decision‐making influence. Gender differences were only found for decision‐making influence, showing that variations in parenting across residence arrangements or between repartnered or single parents were more pronounced for mothers than fathers.

Conclusion

Residence was more strongly related to parenting than repartnering, and the strength and nature of associations varied between parenting behaviors. Influence in decision‐making stood out as a distinct parenting behavior, and also the frequency and obligatory nature of parent–child activities mattered.
Effects of pimobendan on left atrial transport function in cats
Authors: Kochie Samantha L. , Schober Karsten E. , Rhinehart Jaylyn , Winter Randolph L. , Bonagura John D. , Showers Annie , Yildez Vedat
Published: November 2020

Background

Arterial thromboembolism is a sequela of hypertrophic cardiomyopathy (HCM) in cats related to left atrial (LA) enlargement and dysfunction.

Hypothesis

Pimobendan improves LA transport function in cats.

Animals

Twenty‐two client‐owned cats with HCM and 11 healthy cats.

Methods

Prospective, double‐blind, randomized, placebo‐controlled clinical cohort study. Cats were randomized to receive either pimobendan (0.25 mg/kg PO q12h) or placebo for 4 to 7 days. Nineteen echocardiographic variables of LA size and function were evaluated. Statistical comparisons included t tests, analysis of variance, and multivariable analyses.

Results

Peak velocity of left auricular appendage flow (LAapp peak; mean ± SD, 0.85 ± 0.20 vs 0.71 ± 0.22 m/s; P = .01), maximum LA volume (P = .03), LA total emptying volume (P = .03), peak velocity of late diastolic transmitral flow (A peak velocity; 0.77 ± 0.12 vs 0.62 ± 0.17 m/s; P = .05), and A velocity time integral (A VTI; 3.05 ± 0.69 vs 3.37 ± 0.49; P = .05) were increased after pimobendan. Mean change after pimobendan was larger in cats with HCM compared to healthy cats for LA fractional shortening (2.1% vs −2.1%; P = .05), A VTI (0.58 vs 0.01 cm; P = .01), LAapp peak (0.20 vs 0.02 m/s; P = .02), LA kinetic energy (3.51 vs −0.10 kdynes‐cm; P = .05), and LA ejection force (1.93 vs −0.07 kdynes; P = .01) in the multivariable model. The stronger effect of pimobendan in cats with HCM was independent of LA size.

Conclusions and Clinical Importance

We identified positive, albeit minor, effects of pimobendan on LA function in cats with HCM. Whether or not treatment with pimobendan decreases the risk of cardiogenic embolism deserves further study.
Maritime CBMs as Soft Deterrence in Northeast Asia: A Sea of Paradox and its Remedies
Authors: Ban Kil Joo
Published: November 2020

Sources of conflict exist in Northeast Asian waters, ranging from maritime territorial disputes, such as the Senkaku (Diaoyu) Islands, to friction over maritime airspace within air defense identification zones (ADIZs), and in the great power competition between the United States and China. Sources of cooperation, such as anti‐piracy coordination, also exist in these waters. These two seas coexist despite their incompatible nature. How to guarantee maritime security in the region had been examined primarily through the concept of deterrence, which relies on a coercion‐led mechanism. A functional balance of military capabilities can play a pivotal role in preventing disputes from escalating into military conflict. Without proper transparent measures, however, states in the region can face a security‐dilemma in the form of an unstoppable arms race. Thus, military armament should be supported by confidence armament for maritime security in Northeast Asia. When hard deterrence is implemented simultaneously with maritime confidence‐building measures (MCBMs) as a soft deterrence, which is a voluntary‐basis mechanism, maritime security is more likely to be guaranteed. Likewise, when both military and confidence‐building measures are made simultaneously, the logic of smart deterrence is more likely to be successfully manifested, contributing to making regional stability more sustainable.
Inverse scattering transform for the focusing nonlinear Schrödinger equation with counterpropagating flows
Authors: Biondini Gino , Lottes Jonathan , Mantzavinos Dionyssios
Published: November 2020

The inverse scattering transform for the focusing nonlinear Schrödinger equation is presented for a general class of initial conditions whose asymptotic behavior at infinity consists of counterpropagating waves. The formulation takes into account the branched nature of the two asymptotic eigenvalues of the associated scattering problem. The Jost eigenfunctions and scattering coefficients are defined explicitly as single‐valued functions on the complex plane with jump discontinuities along certain branch cuts. The analyticity properties, symmetries, discrete spectrum, asymptotics, and behavior at the branch points are discussed explicitly. The inverse problem is formulated as a matrix Riemann‐Hilbert problem with poles. Reductions to all cases previously discussed in the literature are explicitly discussed. The scattering data associated to a few special cases consisting of physically relevant Riemann problems are explicitly computed.