bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells exhibit unexpectedly low discriminatory power and can respond to ultra-low affinity peptide-MHC ligands
Authors: Pettmann Johannes , Abu-Shah Enas , Kutuzov Mikhail , Wilson Daniel B. , Dustin Michael L. , Davis Simon J. , van der Merwe P. Anton , Dushek Omer 
Published: November 2020

AbstractT cells use their T cell receptors (TCRs) to discriminate between peptide MHC (pMHC) ligands that bind with different affinities but precisely how different remains controversial. This is partly because the affinities of physiologically relevant interactions are often too weak to measure. Here, we introduce a surface plasmon resonance protocol to measure ultra-low TCR/pMHC affinities (KD~ 1000μM). Using naïve, memory, and blasted human CD8+T cells we find that their discrimination power is unexpectedly low, in that they require a large >100-fold decrease in affinity to abolish responses. Interestingly, the discrimination power reduces further when antigen is presented in isolation on artificial surfaces but can be partially restored by adding ligands to CD2 or LFA-1. We were able to fit the kinetic proof-reading model to our data, yielding the first estimates for both the time delay (2.8 s) and number of biochemical steps (2.67). The fractional number of steps suggest that one of the proof-reading steps is not easily reversible.
Exploring new roles for actin upon LTP induction in dendritic spines
Authors: Bonilla-Quintana Mayte , Wörgötter Florentin 
Published: November 2020

AbstractDendritic spines, small protrusions of the dendrites, enlarge upon LTP induction, linking morphological and functional properties. Although the role of actin in spine enlargement has been well studied, little is known about its relationship with mechanical membrane properties, such as membrane tension, which is involved in many cell processes, like exocytosis. Here, we use a 3D model of the dendritic spine to investigate how polymerization of actin filaments can effectively elevate the membrane tension to trigger exocytosis in a domain close to the tip of the spine. Moreover, we show that the same pool of actin promotes full membrane fusion after exocytosis and spine stabilization.
Assessing Conservation of Alternative Splicing with Evolutionary Splicing Graphs
Authors: Zea Diego Javier , Laskina Sofya , Baudin Alexis , Richard Hugues , Laine Elodie 
Published: November 2020

AbstractUnderstanding how protein function has evolved and diversified is of great importance for human genetics and medicine. Here, we tackle the problem of describing the whole transcript variability observed in several species by generalising the definition of splicing graph. We provide a practical solution to building parsimoniousevolutionarysplicing graphs where each node is a minimal transcript building block defined across species. We show a clear link between the functional relevance, tissue-regulation and conservation of AS events on a set of 50 genes. By scaling up to the whole human protein-coding genome, we identify a few thousands of genes where alternative splicing modulates the number and composition of pseudo-repeats. We have implemented our approach in ThorAxe, an efficient, versatile, and robust computational tool freely available athttps://github.com/PhyloSofS-Team/thoraxe. The results are accessible and can be browsed interactively athttp://www.lcqb.upmc.fr/ThorAxe.
Phenotypic plasticity of ER+ breast cancer in the bone microenvironment
Authors: Bado Igor L. , Wang Hai , Sarkar Poonam , Liu Jun , Wu William , Zhang Weijie , Lo Hin-Ching , Muscallera Aaron , Janghorban Mahnaz , Kim Ik-Sun , Singh Swarnima , Goldstein Amit , Singh Purba , Shixia Huang , Waleed Gaber M. , Ellis Matthew J. , Zhang Xiang H.-F. 
Published: November 2020

SummaryER+ breast cancer exhibits a strong bone-tropism in metastasis. How the bone microenvironment impacts the ER signaling and endocrine therapies remains poorly understood. Here, we discover that the osteogenic niche transiently reduces ER expression and activities specifically in bone micrometastases (BMMs), leading to endocrine resistance. This is mediated by gap junctions and paracrine FGF/PDGF signaling, which together generate a stable “memory”: cancer cells extracted from bone remain resistant to endocrine therapies for several generations. Using single cell-derived populations (SCPs), we demonstrated that this process is independent of clonal selection, and represents an EZH2-mediated epigenomic reprogramming. EZH2 drives ER+ BMMs toward a basal and stem-like state. EZH2 inhibition reverses endocrine resistance. Our data demonstrates how epigenomic adaptation to the bone microenvironment drives phenotypic plasticity of metastatic seeds and alters their therapeutic responses together with clonal selection, and provides insights into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies.
Thermal acclimation alters the roles of Na+/K+-ATPase activity in a tissue-specific manner inDrosophila melanogaster
Authors: Cheslock Alexandra , Andersen Mads Kuhlmann , MacMillan Heath A. 
Published: November 2020

AbstractInsects, like the model speciesDrosophila melanogaster, lose neuromuscular function and enter a state of paralysis (chill coma) at a population- and species-specific low temperature threshold that is decreased by cold acclimation. Entry into this coma is related to a spreading depolarization in the central nervous system, while recovery involves restoration of electrochemical gradients across muscle cell membranes. The Na+/K+-ATPase helps maintain ion balance and membrane potential in both the brain and hemolymph (surrounding muscles), and changes in thermal tolerance traits have therefore been hypothesized to be closely linked to variation in the expression and/or activity of this pump in multiple tissues. Here, we tested this hypothesis by measuring activity and thermal sensitivity of the Na+/K+-ATPase at the tagma-specific level (head, thorax and abdomen) in warm-(25°C) and cold-acclimated (15°C) flies by Na+/K+-ATPase activity at 15, 20, and 25°C. We relate differences in pump activity to differences in chill coma temperature, spreading depolarization temperature, and thermal dependence of muscle cell polarization. Differences in pump activity and thermal sensitivity induced by cold acclimation varied in a tissue-specific manner: While cold-acclimated flies had decreased thermal sensitivity of Na+/K+-ATPase that maintains activity at low temperatures in the thorax (mainly muscle), activity instead decreased in the heads (mainly brain). We argue that these changes may assist in maintenance of K+homeostasis and membrane potential across muscle membranes and discuss how reduced Na+/K+-ATPase activity in the brain may counterintuitively help insects delay coma onset in the cold.
C. elegansprovide milk for their young
Authors: Kern Carina C. , Townsend StJohn , Salzmann Antoine , Rendell Nigel B. , Taylor Graham W. , Comisel Ruxandra M. , Foukas Lazaros C. , Bähler Jürg , Gems David 
Published: November 2020

AbstractAdultC. eleganshermaphrodites exhibit severe senescent pathology that begins to develop within days of reaching sexual maturity (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Wang et al., 2018). For example, after depletion of self-sperm, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis (pseudocoelomic lipoprotein pools, PLPs) (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Sornda et al., 2019). These senescent pathologies are promoted by insulin/IGF-1 signalling (IIS), which also shortens lifespan (Ezcurra et al., 2018; Kenyon, 2010). This pattern of rapid and severe pathology in organs linked to reproduction is reminiscent of semelparous organisms where massive reproductive effort leads to rapid death (reproductive death) as in Pacific salmon (Finch, 1990; Gems et al., 2020). Moreover, destructive conversion of somatic biomass to support reproduction is a hallmark of reproductive death (Gems et al., 2020). Yet arguing against the occurrence of reproductive death inC. elegansis the apparent futility of post-reproductive yolk production. Here we show that this effort is not futile, since post-reproductive mothers vent yolk through their vulva, which is consumed by progeny and supports their growth; thus vented yolk functions as a milk, andC. elegansmothers exhibit a form of lactation. Moreover, IIS promotes lactation, thereby effecting a costly process of resource transfer from postreproductive mothers to offspring. These results support the view thatC. eleganshermaphrodites exhibit reproductive death involving a self-destructive process of lactation that is promoted by IIS. They also provide new insight into how the strongly life-shortening effects of IIS inC. elegansevolved.
Development of a cricket paralysis virus-based system for inducing RNA interference-mediated gene silencing inDiaphorina citri
Authors: Matsumura Emilyn E. , Nigg Jared C. , Henry Elizabeth M. , Falk Bryce W. 
Published: November 2020

AbstractDiaphorina citri, the Asian citrus psyllid, is the insect vector of the phloem-limited bacterium ‘CandidatusLiberibacter asiaticus’, which causes the most devastating citrus disease worldwide: Huanglongbing (HLB). An efficient cure for HLB is still not available and the management of the disease is restricted to the use of pesticides, antibiotics and eradication of infected plants. Plant- and insect-infecting viruses have attracted increasing attention for their potential to manipulate traits in insects, especially insect vectors of plant pathogens. However, so far there are no insect virus-based vectors available for use inD. citri. Cricket paralysis virus (CrPV) is a well-studied insect-infecting dicistrovirus with a wide host range and has been used as a model in previous translational studies. In this work, we demonstrate for the first time that CrPV is infectious and pathogenic toD. citri.We show that specific amino acid mutations in the CrPV primary cleavage DvExNPGP motif resulted in a viral mutant that was attenuated compared to wild-type CrPV during infection of eitherDrosophilacells line or adultD. citriinsects. This attenuated CrPV mutant was then used as the backbone for engineering a recombinant CrPV-based vector to specifically alterD. citrigene expression via the RNA interference (RNAi) pathway, a technology called Virus Induced Gene Silencing (VIGS). As proof-of-concept, we engineered recombinant CrPV-based vectors carrying nucleotide sequences derived from a previously reportedD. citritarget gene: the inhibitor of apoptosis gene (IA). RT-qPCR analysis of insects either microinjected or fed with the recombinant CrPV mutants showed decreased IA gene expression as soon as viral replication was detected, indicating that the engineered CrPV-based VIGS system enables functional gene silencing inD. citri. This novel insect virus-based tool is easily amenable to genomic modification and represents a technical advance for understanding interactions between insect virus-based VIGS systems andD. citri.
Role of β-arrestin-2 in short- and long-term opioid tolerance in the dorsal root ganglia
Authors: Muchhala Karan H. , Jacob Joanna C. , Dewey William L. , Akbarali Hamid I. 
Published: November 2020

Abstractβ-arrestin-2 has been implicated in the mechanism of opioid-induced antinociceptive tolerance. G-protein-biased agonists with reduced β-arrestin-2 activation are being investigated as safer alternatives to clinically-used opioids. Opioid-induced analgesic tolerance is classically considered as centrally-mediated, but recent reports implicate nociceptive dorsal root ganglia (DRG) neurons as critical mediators in this process. Here, we investigated the role of β-arrestin-2 in the mechanism of opioid tolerance in DRG nociceptive neurons using β-arrestin-2 knockout mice and the G-protein-biased μ-opioid receptor agonist, TRV130. Whole-cell current-clamp electrophysiology experiments revealed that 15-18-hour overnight exposure to 10 μM morphinein vitroinduced acute tolerance in β-arrestin-2 wild-type but not knockout DRG neurons. Furthermore, in wild-type DRG neurons circumventing β-arrestin-2 activation by overnight treatment with 200 nM TRV130 attenuated tolerance. Similarly, in β-arrestin-2 knockout male mice acute antinociceptive tolerance induced by 100 mg/kg morphine s.c. was prevented in the warm-water tail-withdrawal assay. Treatment with 30 mg/kg TRV130 s.c. also inhibited antinociceptive tolerance in wild-type mice. Alternately, in β-arrestin-2 knockout DRG neurons tolerance induced by 7-dayin vivoexposure to 50 mg morphine pellet was conserved. Likewise, β-arrestin-2 deletion did not mitigatein vivoantinociceptive tolerance induced by 7-day exposure to 25 mg or 50 mg morphine pellet in both female or male mice, respectively. Consequently, these results indicated that β-arrestin-2 mediates acute but not chronic opioid tolerance in DRG neurons and to antinociception. This suggests that opioid-induced antinociceptive tolerance may develop even in the absence of β-arrestin-2 activation, and thus significantly affect the clinical utility of biased agonists.
The influence of social media usage, self-image congruity and self-esteem on conspicuous online consumption among millennials
Authors: Burnasheva Regina , Suh Yong Gu 
Published: November 2020

PurposeDriven by social comparison and self-congruity theories, this paper's aim was to investigate the associations with Korean millennials' usage of social media, self-image congruity and conspicuous online consumption. The mediating influence of self-image congruity and the moderating effect of self-esteem were also examined.Design/methodology/approachThese data were gathered through an online research portal from 302 Korean millennials. Structural equation modeling (SEM) analyses and moderated mediation analysis using Hayes PROCESS macro were applied to test proposed hypotheses.FindingsThe result of the structural equation analyses showed strong, positive associations between social media usage, self-image congruity and conspicuous online consumption, while self-image congruity also acted as a mediator between Korean millennials' usage of social media and conspicuous online consumption. Moreover, in moderated mediation analysis, the pathway between self-image congruity and conspicuous online consumption was stronger for millennials with higher self-esteem.Originality/valueMillennials' social media usage and conspicuous consumption are widely acknowledged in consumer research. However, little is known about how millennials' social media usage could influence their conspicuous online consumption through mediating and moderating mechanisms such as self-image congruity and self-esteem. This research extends previous studies by analyzing these mechanisms.
Automated assessment of architectural spatial layout configurations using fuzzy logic
Authors: Ezzeldin Mohamed , Assem Ayman , Abdelmohsen Sherif 
Published: November 2020

PurposeConventional approaches of evaluating spatial layout configurations typically involved universal understandings of aspects like connectivity, proximity and visibility, while possibly discarding both partially true solutions and ranges of parameters affecting detailed spatial relations. With the growing need to address spatial uncertainty and ambiguity, the incorporation of methods that embrace soft qualities in design is becoming increasingly significant in spatial layout planning.Design/methodology/approachThe authors introduce a fuzzy-based approach for the automated assessment of architectural spatial layout configurations while addressing ambiguity in layout design. The authors evaluate soft interdependent design qualities like connectedness, enclosure and spaciousness to satisfy multiple mutually inclusive criteria and account for all logical solutions without discarding likely or less likely solutions. The authors analyze spatial entities, parameters and relations and identify rulesets for logical configurations using linguistic variables, fuzzy sets, membership functions and descriptive rule blocks. As a case study, the authors use grasshopper and fuzzyTECH to represent four pilot layout alternates with varying attributes and a case study focusing on one specific spatial criterion.FindingsMultiple complex and nuanced spatial relations were inferred by evaluating spatial outputs and their inherent discrepancies and correlations, thus confirming the assumption that fuzzy-based systems could potentially satisfy multiple mutually inclusive criteria and account for exhaustive logical solutions without discarding preferable, likely or less likely solutions.Originality/valueMost precedent approaches focus on spatial layout design from an occupancy-centered perspective, where occupancy patterns and possibilities are identified in loosely defined spaces or behavioral usage patterns. The added value in this paper involves including a wide array of spatial inputs to describe soft spatial qualities using nuanced rule-based descriptors.
Do level of tourism development and its type make a difference in residents' perceptions? Learning from Turkish cases
Authors: Karamustafa Kurtulus , Ülker Pembe , Çalhan Harun 
Published: November 2020

PurposeThis study provides insights on the perceptions of residents in destinations offering different tourism products at different levels of tourism development.Design/methodology/approachA total of 1,122 valid responses were gathered through surveys from the residents of three unique destinations, with different levels of tourism development. Non-parametric tests were performed since the data was gathered on an ordinal scale and not distributed normally.FindingsThe tourism perceptions of the residents formed a five-factor structure, namely “socioecological negative”, “socioeconomic positive”, “socioecological development (wellbeing)”, “negative perceptions of tourism” and “tendency to become visitor”. All dimensions except for “socioeconomic positive” differed significantly by destinations in terms of level of tourism development or type of tourism product offered.Research limitations/implicationsResidents' perceptions of tourism differ based on different tourism products and different levels of tourism development of destinations. The residents of the most mature destinations in terms of tourism development have the most negative perceptions of tourism.Originality/valueAlthough there are studies investigating how residents' perceptions differ based on the level of tourism development of destinations, this study, with its holistic approach, aims to provide insights on how residents' perceptions of tourism differ based on the tourism products offered by different destinations. The selected destinations differ from each other in both their level of tourism involvement and products they offer, hence the originality of the current study with its unique contribution to the related body of knowledge.
Dynamic capabilities and competitive advantages as mediator variables between market orientation and business performance
Authors: Correia Ricardo Jorge , Dias José G. , Teixeira Mário Sérgio 
Published: November 2020

PurposeThis paper aims to explore a new causal link between market orientation and business performance by introducing dynamic capabilities as a mediator of the relationship between market orientation and competitive advantages, which ultimately determine business performance.Design/methodology/approachThe mediating roles of dynamic capabilities and competitive advantages are tested with a sample of 1,190 Portuguese firms using a structural equation model.FindingsThe results confirm the hypotheses regarding the mediating roles of the competitive advantages (differentiation and cost leadership) in the relationship between dynamic capabilities and business performance. Additionally, dynamic capabilities also mediate the relationship between market orientation and competitive advantages.Practical implicationsThis study shows that business performance depends on the capacity of firms to collect the best market information on customers and competitors, to disseminate this information throughout their internal structure and ultimately optimize its use to respond appropriately to market challenges and trends. These will provide firms with a set of capabilities and a competitive advantage.Originality/valueThis study provides empirical evidence on the understanding of the relationship between market orientation and performance, through the mediating effects of both dynamic capabilities and competitive advantages.
On the relationship between sport and financial performances: an empirical investigation
Authors: Di Simone Luca , Zanardi Davide 
Published: November 2020

PurposeOur paper shows an empirical analysis of the European football companies to test the association between sport results, proxied by ranking position and financial performance in panel framework (starting from 59 firms over the 2013–2018 time span).Design/methodology/approachWe use panel data models for studying the relationship of our interest and we make no a priori assumption about the strict exogeneity of the covariates and estimate equation using both Random Effects GLS (RE-GLS) and Fixed Effects OLS (FE-OLS) estimations.FindingsOur results suggest there is stable and significant relationship between the two types of performance and that when detectable this is linked in a positive way to the profit maximization of the business model, suggesting that it is more useful for investor remuneration and to increase technical-tactical resources and therefore sports results. Not surprisingly, as for many clubs, concentration effect is relevant while the financial fair play regulation is not. In fact, the current regulation of UEFA authority does not seem to have an impact on sport and financial results.Originality/valueThis work complements literature in several ways. First, we offer new empirical evidence for the association between the sport and financial performance for a panel of the European football companies, listed and not. Second, we show that the persistence of the sport results is strongly correlated with financial performance.
Double-diffusive free convective flow of Casson fluid due to a moving vertical plate with non-linear thermal radiation
Authors: Nandeppanavar Mahantesh M. , M.C. Kemparaju , Raveendra N. 
Published: November 2020

Purpose
This paper aims to report the investigation of over heat and mass transfer of convective Casson fluid flow over a moving vertical plate with nonlinear thermal radiation and convective boundary conditions.

Design/methodology/approach
The main partial differential equations of the flow, heat and concentration profiles were rehabilitated to nonlinear ordinary differential equations by using an appropriate similarity transformation. The resultant nonlinear ordinary differential equations (ODEs) are solved numerically applying fourth-order Runge–Kutta shooting technique and functions of ODE45 from MATLAB.

Findings
The effect of convective heat transfer, buoyancy ratio parameter, nonlinear thermal radiation, Prandtl number, Rayleigh number and Schmidt number over velocity, temperature and concentration profiles, equivalent to abundant somatic parameters were graphically scrutinized.

Originality/value
All the results are very promising and further there is got good agreement of results when compared with earlier published results at limiting conditions.