bluuebunny/crossref_metadata_2025_split huggingface dataset:
Realistic retinal modeling unravels the differential role of excitation and
inhibition to starburst amacrine cells in direction selectivity
Authors: Ezra-Tsur Elishai , Amsalem Oren , Ankri Lea , Patil Pritish , Segev Idan , Rivlin-Etzion Michal 
Published: May 2022

Abstract
Retinal direction-selectivity originates in starburst amacrine cells (SACs),
which display a centrifugal preference, responding with greater depolarization
to a stimulus expanding from soma to dendrites than to a collapsing stimulus.
Various mechanisms were hypothesized to underlie SAC centrifugal preference, but
dissociating them is experimentally challenging and the mechanisms remain
debatable. To address this issue, we developed the Retinal Stimulation Modeling
Environment (RSME), a multifaceted data-driven retinal model that encompasses
detailed neuronal morphology and biophysical properties, retina-tailored
connectivity scheme and visual input. Using a genetic algorithm, we demonstrated
that spatiotemporally diverse excitatory inputs – sustained in the proximal and
transient in the distal processes – are sufficient to generate experimentally
validated centrifugal preference in a single SAC. Reversing these input kinetics
did not produce any centrifugal-preferring SAC. We then explored the
contribution of SAC-SAC inhibitory connections in establishing the centrifugal
preference. SAC inhibitory network enhanced the centrifugal preference, but
failed to generate it in its absence. Embedding a direction selective ganglion
cell (DSGC) in a SAC network showed that the known SAC-DSGC asymmetric
connectivity by itself produces direction selectivity. Still, this selectivity
is sharpened in a centrifugal-preferring SAC network. Finally, we use RSME to
demonstrate the contribution of SAC-SAC inhibitory connections in mediating
direction selectivity and recapitulate recent experimental findings. Thus, using
RSME, we obtained a comprehensive mechanistic understanding of SACs’ centrifugal
preference and its contribution to direction selectivity.
Leveraging Allele-Specific Expression for Therapeutic Response Gene Discovery
in Glioblastoma
Authors: Sen Arko , Prager Briana C. , Park Donglim , Zhu Zhe , Gimple Ryan C. , Bernatchez Jean A. , Beck Sungjun , Clark Alex E. , Siqueira-Neto Jair L. , Rich Jeremy N. , McVicker Graham 
Published: May 2022

ABSTRACT
Glioblastoma is the most prevalent primary malignant brain tumor in adults
and is characterized by poor prognosis and universal tumor recurrence. Effective
glioblastoma treatments are lacking, in part due to somatic mutations and
epigenetic reprogramming that alter gene expression and confer drug resistance.
Here, we interrogated allele-specific expression (ASE) in 43 patient-derived
glioblastoma stem cells (GSCs) to identify recurrently dysregulated genes in
glioblastoma. We identified 118 genes with recurrent ASE preferentially found in
GSCs compared to normal tissues. These genes were enriched for apoptotic
regulators, including Schlafen Family Member 11
(SLFN11). Loss of
SLFN11 gene expression was associated with
aberrant promoter methylation and conferred resistance to chemotherapy and poly
ADP ribose polymerase inhibition. Conversely, low
SLFN11 expression rendered GSCs susceptible to
the oncolytic flavivirus Zika, which suggests a potential alternative treatment
strategy for chemotherapy resistant GBMs.
Whole-genome sequence analysis unveils different origins of European and Asiatic mouflon and domestication-related genes in sheep
Authors: Chen Ze-Hui , Xu Ya-Xi , Xie Xing-Long , Wang Dong-Feng , Aguilar-Gómez Diana , Liu Guang-Jian , Li Xin , Esmailizadeh Ali , Rezaei Vahideh , Kantanen Juha , Ammosov Innokentyi , Nosrati Maryam , Periasamy Kathiravan , Coltman David W. , Lenstra Johannes A. , Nielsen Rasmus , Li Meng-Hua 
Published: May 2022

AbstractThe domestication and subsequent development of sheep are crucial events in the history of human civilization and the agricultural revolution. However, the impact of interspecific introgression on the genomic regions under domestication and subsequent selection remains unclear. Here, we analyze the whole genomes of domestic sheep and all their wild relative species. We found introgression from wild sheep such as the snow sheep and its American relatives (bighorn and thinhorn sheep) into urial, Asiatic and European mouflons. We observed independent events of adaptive introgression from wild sheep into the Asiatic and European mouflons, as well as shared introgressed regions from both snow sheep and argali into Asiatic mouflon before or during the domestication process. We revealed European mouflons arose through hybridization events between a now extinct sheep in Europe and feral domesticated sheep around 6,000 – 5,000 years BP. We also unveiled later introgressions from wild sheep to their sympatric domestic sheep after domestication. Several of the introgression events contain loci with candidate domestication genes (e.g.,PAPPA2,NR6A1,SH3GL3,RFX3andCAMK4), associated with morphological, immune, reproduction or production traits (wool/meat/milk). We also detected introgression events that introduced genes related to nervous response (NEURL1), neurogenesis (PRUNE2), hearing ability (USH2A) and placental viability (PAG11andPAG3) to domestic sheep and their ancestral wild species from other wild species.
Approaches to generating virtual patient cohorts with applications in oncology
Authors: Surendran Anudeep , Sauteur-Robitaille Justin Le , Kleimeier Dana , Gevertz Jana , Wilkie Kathleen , Jenner Adrianne L. , Craig Morgan 
Published: May 2022

ABSTRACTVirtual clinical trials (VCTs) have gained popularity for their ability to rationalize the drug development process using mathematical and computational modelling, and to provide key insights into the mechanisms regulating patient responses to treatment. In this chapter, we cover approaches for generating virtual cohorts with applications in cancer biology and treatment. VCTs are an effective tool for predicting clinical responses to novel therapeutics and establishing effective treatment strategies. These VCTs allow us to capture inter-individual variability (IIV) which can lead to diversity in patient drug responses. Here we discuss three main methodologies for capturing IIV with a VCT. First, we highlight the use of population pharmacokinetic (PopPK) models, which extrapolate from empirical data population PK parameters that best fits the individual variability seen in drug disposition using non-linear mixed effects models. Next, we show how virtual patients may be sampled from a normal distribution with mean and standard deviation informed from experimental data to estimate parameters in a mechanistic model that regulates drug PKs. Lastly, we show how optimization techniques can be used to calibrate virtual patient parameter values and generate the VCT. Throughout, we compare and contrast these methods to provide a broader view of the generation of virtual patients, and to aid the decision-making process for those looking to leverage virtual clinical trials in their research.
A high throughput screen with a clonogenic endpoint to identify radiation modulators of cancer
Authors: Gomes Nathan P. , Frederick Barbara , Jacobsen Jeremy R. , Chapnick Doug , Su Tin Tin 
Published: May 2022

AbstractGomes, N. P., Frederick, B., Jacobsen, J. R., Chapnick. D. and Su, T. T. A high throughput screen with a clonogenic endpoint to identify radiation modulators of cancer. Radiat. Res.Clonogenic assays evaluate the ability of single cells to proliferate and form colonies. This process approximates the regrowth and recurrence of tumors after treatment with radiation or chemotherapy, and thereby provides a drug discovery platform for compounds that block this process. However, because of their labor-intensive and cumbersome nature, adapting canonical clonogenic assays for high throughput screening (HTS) has been challenging. We overcame these barriers by developing an integrated system that automates cell- and liquid-handling, irradiation, dosimetry, drug administration, and incubation. Further, we developed a fluorescent live-cell based automated colony scoring methodology that identifies and counts colonies precisely based upon actual nuclei number rather than colony area, thereby eliminating errors in colony counts caused by radiation induced changes in colony morphology. We identified 13 cell lines from 7 cancer types, where radiation is a standard treatment module, that exhibit identical radiation and chemoradiation response regardless of well format and are amenable to miniaturization into small-well HTS formats. We performed pilot screens through a 1584 compound NCI Diversity Set library using two cell lines representing different cancer indications. Radiation modulators identified in the pilot screens were validated in traditional clonogenic assays, providing proof-of-concept for the screen. The integrated methodology, hereafter ‘clonogenic HTS’, exhibits excellent robustness (Z’ values >0.5) and shows high reproducibility (>95%). We propose that clonogenic HTS we developed can function as a drug discovery platform to identify compounds that inhibit tumor regrowth following radiation therapy, to identify new efficacious pair-wise combinations of known oncologic therapies, or to identify novel modulators of approved therapies.
CspZ FH-binding sites as epitopes promote antibody-mediated Lyme borreliae clearance
Authors: Chen Yi-Lin , Marcinkiewicz Ashley L. , Nowak Tristan A. , Kundu Rakhi Tyagi , Liu Zhuyun , Strych Ulrich , Bottazzi Maria-Elena , Chen Wen-Hsiang , Lin Yi-Pin 
Published: May 2022

ABSTRACTTransmitted by ticks, the bacterium Borrelia burgdorferi sensu lato (Bbsl) is the causative agent of Lyme disease (LD), the most common vector-borne disease in the Northern hemisphere. No effective vaccines are currently available. Bbsl produces the CspZ protein that binds to the complement inhibitor, Factor H (FH), promoting evasion of the host complement system. We previously showed that while vaccination with CspZ did not protect mice from Bb infection, mice can be protected after immunization with CspZ-Y207A/Y211A (CspZ-YA), a CspZ mutant protein without FH-binding activity. To further study the mechanism of this protection, herein we evaluated both poly-and monoclonal antibodies recognizing CspZ FH-binding or non-FH-binding sites. We found that the anti-CspZ antibodies that recognize the FH-binding sites (i.e., block FH-binding activity) more efficiently eliminate Bbsl in vitro than those that bind to the non-FH-binding sites, and passive inoculation with anti-FH binding site antibodies eradicated Bbsl in vivo. Antibodies against non-FH-binding sites did not have the same effect. These results emphasize the importance of CspZ FH-binding sites in triggering a protective antibody response against Bbsl in future LD vaccines.
ChromGene: Gene-Based Modeling of Epigenomic Data
Authors: Jaroszewicz Artur , Ernst Jason 
Published: May 2022

AbstractBackgroundVarious computational approaches have been developed to annotate epigenomes on a per-position basis by modeling combinatorial and spatial patterns within epigenomic data. However, such annotations are less suitable for gene-based analyses, in which a single annotation for each gene is desired.ResultsTo address this, we developed ChromGene, which annotates genes based on the combinatorial and spatial patterns of multiple epigenomic marks across the gene body and flanking regions. Specifically, ChromGene models the epigenomics maps using a mixture of hidden Markov models learned de novo. Using ChromGene, we generated annotations for the human protein-coding genes for over 100 cell and tissue types. We characterize the different mixture components and their associated gene sets in terms of gene expression, constraint, and other gene annotations. We also characterize variation in ChromGene gene annotations across cell and tissue types.ConclusionsWe expect that the ChromGene method and provided annotations will be a useful resource for gene-based epigenomic analyses.
Genome-wide identification of microsatellite markers and their application in genetic studies of wolfberry (Lycium barbarum)
Authors: Yin Yue , Qin Xiaoya , Zhao Jianhua , An Wei , Li Yanlong , Fan Yunfang , Wang Yajun , Cao Youlong 
Published: May 2022

AbstractThe wolfberry (Lycium barbarum) has been an important traditional Chinese food and medicine for hundreds of years. However, few microsatellite markers have been developed for assessing the genetic diversity and genetic linkage maps among Lycium species in genetic research. In the present study, a total of 397,558 microsatellite loci were identified from whole wolfberry genome sequences with an overall density of 212.1 Mb/SSRs. Dinucleotide microsatellites were the most abundant type, representing 58.26% of the total microsatellite loci, followed by tri-, penta-, hexa-, and tetranucleotide. The AT motifs were the most abundant of all nucleotide repeat motifs, accounting for 44.52%. A set of 600 primer pairs were synthesized and preliminarily screened among four wolfberry accessions. Of these, 277 primer pairs were selected as polymorphic markers. In total, 22 highly polymorphic SSR markers were selected for the characterization of genetic diversity among 37 wolfberry accessions. A total of 323 alleles were detected with an average of 14.7 alleles per marker. The polymorphic information content (PIC) values ranged from 0.612 to 0.911. The dendrogram revealed that the phylogenetic relationships among these wolfberry accessions were consistent with their genetic background. Thus, the large number of genome-wide microsatellite markers developed from the wolfberry genome provides a valuable resource for genetic diversity, genetic map construction, quantitative trait locus (QTL) mapping, and marker-assisted selection breeding in Lycium species.
How environmental gain messages affect cause involvement, attitude and behavioural intentions: the moderating effects of CSR scepticism and biospheric values
Authors: Stadlthanner Katja Anna , Andreu Luisa , Font Xavier , Ribeiro Manuel Alector , Currás-Pérez Rafael 
Published: May 2022

PurposeThis study examines the direct effect of outcome message frames (gain vs loss) on cause involvement and the moderating roles of consumers' corporate social responsibility (CSR) scepticism and biospheric values. Furthermore, the authors analyse (1) the effects of gain-framed messages on consumer attitudes towards an environmental cause (i.e. the use of reusable coffee cups) and towards the company promoting the cause (a coffee shop chain); (2) how consumer attitudes towards the cause affect their attitudes towards the company; and (3) how consumer attitudes towards both the cause and the company affect their behavioural intentions towards both the cause and the company.Design/methodology/approachUsing a 2 × 1 scenario-based, experimental design with a gain vs loss stimuli, Study 1 (n = 466) examines the moderating effects of CSR scepticism and biospheric values on the relationship between message framing and consumer cause involvement. Using gain-framed stimuli, Study 2 (n = 958) analyses the effects of cause involvement variations on attitudes and behaviours, through structural equation modelling.FindingsGain-framed messages are more effective than loss-framed messages at increasing cause involvement in consumers. Both CSR scepticism and biospheric values moderate the relationship between gain-framed messages and cause involvement. Cause involvement enhances consumer attitudes towards both the cause and the company promoting it, while company attitudes towards a cause positively influence consumers' behavioural intentions.Originality/valueThis study recommends that environmental CSR advertising managers should use gain-framed messages to positively influence consumer cause involvement.
Leading peers in an academic setting: insights from the front lines
Authors: Haskins Mark E. 
Published: May 2022

PurposeThis article highlights and discusses numerous, specific leadership attributes that contribute greatly to enabling a university faculty member to be an effective leader of a group of their peers. As such, this article provides additional insights into the important construct of “transcollegial leadership” (Burns and Mooney, 2018).Design/methodology/approachThe personal “reflections on practice” (Schon, 1983) presented here are based on 40+ years of observing and experiencing university faculty leading groups of peers as well as numerous personal experiences of serving in such a leadership role.FindingsThis article presents a robust array of specific, real-world-based insights that can contribute to enhancing the effectiveness of a leader of peers in a higher education institutional setting. Moreover, the ideas presented are offered to leaders of academic institutions as foci for potential faculty development initiatives and discussions. The ideas presented are clustered into six categories – process, resolve, integrity, mindset, excitement/energy, and respect.Practical implicationsThe actions and ideas presented pertaining to a university faculty member's capability to effectively lead a group of peers are widely and immediately actionable. The insights presented are also amenable to ongoing faculty development activities and discussions.Originality/valueThis article addresses the common challenge of effectively leading a group of one's faculty peers in an academic setting. As such, the article extends and embellishes the conceptual, institutional-level perspective presented by Burns and Mooney (2018) in this journal.
Keratosis pilaris and filaggrin loss‐of‐function mutations in patients with atopic dermatitis – Results of a Finnish cross‐sectional study
Authors: Salava Alexander , Salo Ville , Remitz Anita 
Published: May 2022

AbstractKeratosis pilaris (KP) associates with epidermal barrier defects in atopic dermatitis (AD) but its role in disease severity and concomitant atopic diseases seems to vary between populations. We performed a cross‐sectional observational study with 502 randomly selected AD patients of a Finnish tertiary health care center. At a single clinical examination, disease severity (Rajka Langeland severity score and EASI), clinical signs and patient history were evaluated and total IgE levels and frequent filaggrin (FLG) loss‐of‐function mutations were investigated. There was no link with disease severity (p = 0.649, 95% CI 0.569–0.654), asthma (p = 0.230, 95% CI 0.206–0.281) or atopic sensitization (p = 0.351, 95% CI 0.309–0.392). Keratosis pilaris was significantly associated with palmar hyperlinearity (p < 0.000, 95% CI 0.000–0.006, OR 4.664, 95% CI 2.072–10.496) and the filaggrin loss‐of‐function mutation 2282del4 (p < 0.000, 95% CI 0.000–0.009, OR 4.917, 95%CI 1.961–12.330). The prevalence of KP in the cohort was generally low and KP seems to be infrequent in Finnish AD patients. This may be explained by the fact that the tested FLG loss‐of‐function mutations are rarer in the Finnish population compared for example, with central Europe or Asia. Mutations in other locations of the FLG gene or other genes of the epidermal barrier may play a more important role.
Children's version of the systemic clinical outcome and routine evaluation (C‐SCORE): Exploring the psychometric qualities in the Portuguese context
Authors: Vilaça Margarida , Veloso Bruna , Stratton Peter , Relvas Ana Paula 
Published: May 2022

AbstractCurrent literature presents a gap in family functioning assessment instruments directed to children. The Child Systemic Clinical Outcome and Routine Evaluation (C‐SCORE) is a self‐report instrument, based on the original SCORE‐15, that measures different aspects of family functioning from the child's perspective. This study aims to explore the psychometric qualities of the Portuguese version of C‐SCORE using a sample of 119 children, aged 8–11 years, recruited from public (state) schools located in North Portugal. Results showed good internal consistency for the total scale and were consistent with the original factorial structure. Correlation analyses using the Perception Scale of Parenting Communication – Children (COMPA‐C) provided support for convergent validity. This study represents the first psychometric evaluation of the C‐SCORE using a sample of Portuguese children, with exploratory results suggesting that this version presents acceptable psychometric qualities, and may be especially useful to assess family functioning from the child's view.
Enhanced electrocaloric response and energy storage performance of Li‐substituted BaTiO3 ceramics
Authors: Sarraf Sonu , Singh Satyendra 
Published: May 2022

AbstractRecently, ferroelectric and antiferroelectric ceramic materials have gained a lot of interest for the development of environment‐friendly highly‐efficient electrocaloric refrigeration and energy‐storage devices. In this work, lead‐free Ba1−xLixTiO3 ceramics with x = 0, 0.01, 0.02, 0.03, 0.04, and 0.05 were synthesized by the conventional solid‐state reaction method, and the effect of Li doping on dielectric, leakage current, ferroelectric, electrocaloric, and energy storage properties of BaTiO3 ceramics was systematically investigated. The XRD and Raman studies confirmed that the structure of Ba1−xLixTiO3 remains tetragonal as for BaTiO3. The Li substitution shifted the phase transition (TC) of BaTiO3 slightly towards the lower temperature side. Significant drop in leakage current was observed with an addition of Li content. The maximum values of the electrocaloric effect (ΔT), electrocaloric responsivity, and coefficient of performance were found to be 1.44 K, 0.24 × 10−6 K m/V, and 5.75, respectively, for x = 0.04 at an applied field of 60 kV/cm near the Curie temperature. The maximal value of energy storage density was found to be 0.42 J/cm3 with an energy storage efficiency of 60% for x = 0.05. Our results suggested that lead‐free Ba1−xLixTiO3 ceramic material is a promising candidate for potential applications in solid‐state refrigeration technology and high‐efficiency energy storage devices.
Must We Vaccinate the Most Vulnerable? Efficiency, Priority, and Equality in the Distribution of Vaccines
Authors: Curran Emma J. , John Stephen D. 
Published: May 2022

ABSTRACTIn this article, we aim to map out the complexities which characterise debates about the ethics of vaccine distribution, particularly those surrounding the distribution of the COVID‐19 vaccine. In doing so, we distinguish three general principles which might be used to distribute goods and two ambiguities in how one might wish to spell them out. We then argue that we can understand actual debates around the COVID‐19 vaccine – including those over prioritising vaccinating the most vulnerable – as reflecting disagreements over these principles. Finally, we shift our attention away from traditional discussions of distributive justice, highlighting the importance of concerns about risk imposition, special duties, and social roles in explaining debates over the COVID‐19 vaccine. We conclude that the normative complexity this article highlights deepens the need for decision‐making bodies to be sensitive to public input.