bluuebunny/crossref_metadata_2025_split huggingface dataset:
NestedBD: Bayesian Inference of Phylogenetic Trees From Single-Cell DNA Copy Number Profile Data Under a Birth-Death Model
Authors: Liu Yushu , Edrisi Mohammadamin , Ogilvie Huw A. , Nakhleh Luay 
Published: January 2022

AbstractCopy number aberrations (CNAs) are ubiquitous in many types of cancer. Inferring CNAs from cancer genomic data could help shed light on the initiation, progression, and potential treatment of cancer. While such data have traditionally been available via “bulk sequencing”, the more recently introduced techniques for single-cell DNA sequencing (scDNAseq) provide the type of data that makes CNA inference possible at the single-cell resolution.In this paper, we introduce a new birth-death evolutionary model of CNAs as well as a Bayesian method, NestedBD, for the inference of evolutionary trees (topologies and branch lengths with relative mutation rates) from single-cell data under this model. We assessed the accuracy of our method on both simulated and biological data and compared it to the accuracy of two standard phylogenetic tools, namely neighbor-joining and maximum parsimony (MP). We show through simulations that our method infers more accurate topologies and branch lengths. We also studied the ancestral state reconstruction accuracy with the birth-death evolutionary model and found it outperformed MP. Finally, running all three methods on a colorectal cancer data set, we observed that among all three methods, only the phylogeny inferred by NestedBD clearly separated the primary tumor cells from the metastatic ones, providing a more plausible history of the tumor cells.
Neuroanatomical correlates of polygenic risk for Parkinson’s Disease
Authors: Abbasi Nooshin , Tremblay Christina , Rajimehr Reza , Yu Eric , Markello Ross D , Shafiei Golia , Khatibi Nina ,   The ENIGMA-Parkinson’s study, Jahanshad Neda , Thompson Paul M. , Gan-Or Ziv , Misic Bratislav , Dagher Alain 
Published: January 2022

AbstractParkinson ‘s Disease (PD) is heritable, however how genetic risk confers vulnerability remains mostly unknown. Here we use genetic and neuroimaging measures from 20,000 healthy adults from the UK Biobank to show that PD polygenic risk score (PRS) is associated with cortical thinning in a pattern that resembles cortical atrophy seen in PD. Conversely, PD PRS is associated with a global increase in cortical surface area. We also show that the genetically determined cortical thinning profile overlaps with the expression of genes associated with synaptic signaling, is dependent on anatomical connectivity and on regional expression of the most significant PD risk genes. Despite identical PRS distributions in males and females, only males show the associated brain features, possibly explaining the sex disparity in PD. We discuss potential mechanisms linking genetic risk to cortical thickness and surface area, and suggest that the divergent effects may reflect separate routes of genetic vulnerability.
EXTRACELLULAR MATRIX REMODELING IN ATOPIC DERMATITIS HARNESSES THE ONSET OF AN ASTHMATIC PHENOTYPE AND IS A POTENTIAL CONTRIBUTOR TO THE ATOPIC MARCH
Authors: Graff Patrick , Wilzopolski Jenny , Voss Anne , Blimkie Travis M. , Weiner January , Kershaw Olivia , Panwar Preety , Hackett Tillie , Brömme Dieter , Loyal Lucie , Thiel Andreas , Beule Dieter , Hancock Robert E.W. , Gruber Achim D. , Bäumer Wolfgang , Hedtrich Sarah 
Published: January 2022

AbstractThe development of atopic dermatitis (AD) in infancy, and subsequent allergic rhinitis, food allergies, and asthma in later childhood, is known as the atopic march. The mechanism is largely unknown, yet the course of disease indicates the contribution of inter-epithelial crosstalk, through to the onset of inflammation in the skin and progression to another mucosal epithelium.Here, we investigated if and how skin-lung epithelial crosstalk could contribute to the development of the atopic march. First, we emulated this inter-epithelial crosstalk through indirect co-culture of bioengineered atopic-like skin disease models and three-dimensional bronchial epithelial models triggering an asthma-like phenotype in the latter. A subsequent secretome analysis identified throm-bospondin-1, CD44, complement factor C3, fibronectin, and syndecan-4 as potentially relevant skin-derived mediators. As these mediators are extracellular matrix (ECM)-related proteins, we then studied the involvement of the ECM, unveiling distinct proteomic, transcriptomic, and ultrastructural differences in atopic samples. The latter indicated ECM remodeling triggering the release of the above-mentioned mediators. In addition to pro-inflammatory effects in lung tissue, the ECM mediators also exert distinct effects on CD4+ T cells. In vivo mouse data showed that exposure to these mediators over seven days dysregulated activated circadian clock genes which have been previously discussed in the context of atopic diseases and asthma development.We hypothesize the existence of a skin-lung axis that could contribute to the atopic march driven by skin ECM remodeling.One Sentence SummaryAtopic skin harbors the progression of atopic diseases to lung tissue through a skin-lung axis that contributes to the atopic march via extracellular matrix remodeling.
SUMO/deSUMOylation of the BRI1 brassinosteroid receptor modulates plant growth responses to temperature
Authors: Naranjo-Arcos Maria , Srivastava Moumita , Bhardwarj Mansi , Sadanandom Ari , Vert Grégory 
Published: January 2022

ABSTRACTBrassinosteroids (BRs) are a class of steroid molecules perceived at the cell surface that act as plant hormones. The BR receptor BRI1 offers a model to understand receptor-mediated signaling in plants and the role of post-translational modifications. Here we identify SUMOylation as a new modification, targeting BRI1 to regulate its activity. BRI1 is SUMOylated in planta on two lysine residues and the levels of BRI1-SUMO conjugates are controlled by the Desi3a SUMO protease. We demonstrate that BRI1 is deSUMOylated at elevated temperature by Desi3a, leading to increased BRI1 interaction with the negative regulator of BR signaling BIK1 and enhancing BRI1 endocytosis. Loss of Desi3a or BIK1 results in increased response to temperature elevation, indicating that BRI1 deSUMOylation acts as a safety mechanism necessary to keep temperature responses in check. Altogether, our work establishes BRI1 deSUMOylation as a molecular crosstalk mechanism between temperature and BR signaling, allowing plants to translate environmental inputs into growth response.SIGNIFICANCE STATEMENTThe brassinosteroid (BR) receptor BRI1 provides a paradigm for understanding receptor-mediated signaling in plants and contribution of post-translational modifications. Here, we show that BRI carries SUMO modifications in planta on two intracellular lysine residues and that temperature elevation triggers BRI1 deSUMOylation mediated by the Desi3a SUMO protease. Importantly, BRI1 deSUMOylation leads to downregulation of BR signaling via increased BRI1 interaction with the BIK1 negative regulator and increased BRI1 endocytosis. Loss of BRI1 deSUMOylation in desi3a mutants boosts plant responses to heat, indicating that BRI1 deSUMOylation acts as a brake to keep temperature responses in check. Our study uncovers a new post-translational modification targeting BRI1 and sheds light on its functional outcome for environmentally-controlled plant growth.
Nirmatrelvir, an orally active Mpro inhibitor, is a potent inhibitor of SARS-CoV-2 Variants of Concern
Authors: Rai Devendra K. , Yurgelonis Irina , McMonagle Patricia , Rothan Hussin A. , Hao Li , Gribenko Alexey , Titova Elizabeth , Kreiswirth Barry , White Kris M. , Zhu Yuao , Anderson Annaliesa S. , Cardin Rhonda D. 
Published: January 2022

ABSTRACTNew variants of SARS-CoV-2 with potential for enhanced transmission, replication, and immune evasion capabilities continue to emerge causing reduced vaccine efficacy and/or treatment failure. As of January 2021, the WHO has defined five ‘variants of concern’ (VOC): B.1.1.7 (Alpha, α), B.1.351 (Beta, β), P.1 (Gamma, γ), B.1.617.2 (Delta, δ), and B.1.1.529 (Omicron, o). To provide a therapeutic option for the treatment of COVID-19 and variants, Nirmatrelvir, the antiviral component of PAXLOVID™, an oral outpatient treatment recently authorized for conditional or emergency use treatment of COVID-19, was developed to inhibit SARS-CoV-2 replication. Nirmatrelvir (PF-07321332) is a specific inhibitor of coronavirus main protease (Mpro, also referred to as 3CLpro), with potent antiviral activity against several human coronaviruses, including SARS-CoV-2, SARS-CoV, and MERS (Owen et al, Science 2021. doi: 10.1126/science.abl4784). Here, we evaluated PF-07321332 against the five SARS-CoV-2 VOC (α, β, γ, δ,, o) and two Variants of Interest or VOI, C.37 (λ) and B.1.621 (μ), using qRT-PCR in VeroE6 cells lacking the P-glycoprotein (Pgp) multidrug transporter gene (VeroE6 P-gp knockout cells). Nirmatrelvir potently inhibited USA-WA1/2020 strain, and α, β, γ, λ, δ, μ, and o variants in VeroE6 P-gp knockout cells with mean EC50 values 38.0 nM, 41.0 nM, 127.2 nM, 24.9 nM, 21.2 nM, 15.9 nM, 25.7 nM and 16.2 nM, respectively. Sequence analysis of the Mpro encoded by the variants showed ~100% identity of active site amino acid sequences, reflecting the essential role of Mpro during viral replication leading to ability of Nirmatrelvir to exhibit potent activity across all the variants.
Systematic histone H4 replacement inArabidopsis thalianareveals a role for H4R17 in regulating flowering time
Authors: Corcoran Emma Tung , LeBlanc Chantal , Tsang Mia Arias , Sarkiss Anthony , Hu Yuzhao , Pedmale Ullas V. , Jacob Yannick 
Published: January 2022

AbstractDespite the broad array of roles for epigenetic mechanisms on regulating diverse processes in eukaryotes, no experimental system for the direct assessment of histone function is currently available in plants. In this work, we present the development of a genetic strategy inArabidopsis thalianain which modified H4 transgenes can completely replace the expression of endogenous histone H4. Using this strategy, we established a collection of plants expressing different H4 point mutants targeting residues that may be post-translationally modifiedin vivo. To demonstrate the utility of this new H4 mutant collection, we screened it to uncover substitutions in H4 that alter flowering time. We identified different mutations in the tail (H4R17A) and the globular domain (H4R36A, H4R39K, H4R39A, and H4K44A) of H4 that strongly accelerate the floral transition. Furthermore, we found a conserved regulatory relationship between H4R17 and the ISWI chromatin remodeling complex in plants. Similar to other biological systems, H4R17 regulates nucleosome spacing via ISWI. Overall, this work provides a large set of H4 mutants to the plant epigenetics community that can be used to systematically assess histone H4 function inA. thalianaand a roadmap to replicate this strategy for studying other histone proteins in plants.
Central tolerance is impaired in the middle-aged thymic environment
Authors: Lancaster Jessica N. , Keatinge-Clay Damaris L. , Srinivasan Jayashree , Li Yu , Selden Hilary J. , Nam Seohee , Richie Ellen R. , Ehrlich Lauren I. R. 
Published: January 2022

SummaryOne of the earliest hallmarks of immune aging is thymus involution, which not only reduces the number of newly generated and exported T cells, but also alters the composition and organization of the thymic microenvironment. Thymic T-cell export continues into adulthood, yet the impact of thymic involution on the quality of newly generated T-cell clones is not well established. Notably, the number and proportion of medullary thymic epithelial cells (mTECs) and expression of tissue restricted antigens (TRAs) decline with age, suggesting the involuting thymus may not promote efficient central tolerance. Here, we demonstrate that the middle-aged thymic environment does not support rapid motility of medullary thymocytes, potentially diminishing their ability to scan antigen presenting cells that display the diverse self-antigens that induce central tolerance. Consistent with this possibility, thymic slice assays reveal that the middle-aged thymic environment does not support efficient negative selection or regulatory T cell (Treg) induction of thymocytes responsive to either TRAs or ubiquitous self-antigens. This decline in central tolerance is not universal, but instead impacts lower-avidity self-antigens that are either presented at low levels or bind to TCRs with moderate affinities. Additionally, the decline in thymic tolerance by middle-age is accompanied by both a reduction in mTECs and hematopoietic antigen presenting cell subsets that cooperate to drive central tolerance. Thus, age-associated changes in the thymic environment result in impaired central tolerance against moderate avidity self-antigens, potentially resulting in export of increasingly autoreactive naive T cells, with a deficit of Treg counterparts by middle age.
Trypanosoma brucei: A novel system for metacyclogenesis and complete cyclical developmentin vitro
Authors: Nickel Beatrice , Fasler Monika , Brun Reto , Kaminsky Ronald , Roditi Isabel , Jenni Leo 
Published: January 2022

AbstractWe describe anin vitrosystem that allows metacyclogenesis ofT. bruceissp. and is not restricted to certain parasite lines. Following the work of Hirumi and co-workers we developed a modifiedin vitrosystem which allows metacyclogenesis within 7 to 20 days. The most striking changes were the addition of citrate and cis-aconitate, which triggers transformation from bloodstream to procyclic forms, and the elimination of the remaining bloodstream forms by salicylhydroxamic acid and glycerol. A positive feature of this system is thatT. b. gambiensesamples isolated from patients, and transformed to procyclic forms for transport, could give rise to infective forms that could be passaged in rodents.
Identification of differential hypothalamic DNA methylation and gene expression associated with sexual partner preferences in rams
Authors: Bhattacharya Surajit , Amodei Rebecka , Vilain Eric , Roselli Charles E. 
Published: January 2022

AbstractThe sheep is a valuable model to test whether hormone mechanisms that sexually differentiate the brain underlie the expression of sexual partner preferences because as many as 8% of rams prefer same-sex partners. Epigenetic factors such as DNA methylation act as mediators in the interaction between steroid hormones and the genome. Variations in the epigenome could be important in determining morphological or behavior differences among individuals of the same species. In this study, we explored DNA methylation differences in the hypothalamus of male oriented rams (MORs) and female oriented rams (FORs). We employed reduced representation bisulfite sequencing (RRBS) to generate a genome-wide map of DNA methylation and RNA-Seq to profile the transcriptome. We found substantial DNA methylation and gene expression differences between FORs and MORs. Although none of the differentially methylated genes yielded significant functional terms directly associated with sex development, three differentially expressed genes were identified that have been associated previously with sexual behaviors. We hypothesize that these differences are involved in the phenotypic variation in ram sexual partner preferences, whereas future studies will have to find the specific mechanisms. Our results add an intriguing new dimension to sheep behavior that should be useful for further understanding epigenetic and transcriptomic involvement.
Do individuals disclose or withhold information following the same logic: a configurational perspective of information disclosure in social media
Authors: Sun Yongqiang , Zhang Fei , Feng Yafei 
Published: January 2022

PurposeThis paper aimed to explain why individuals still tend to disclose their privacy information even when privacy risks are high and whether individuals disclose or withhold information following the same logic.Design/methodology/approachThis study develops a configurational decision tree model (CDTM) for precisely understanding individuals' decision-making process of privacy disclosure. A survey of location-based social network service (LBSNS) users was conducted to collect data, and fuzzy-set qualitative comparative analysis (fsQCA) was adopted to validate the hypotheses.FindingsThis paper identified two configurations for high and low disclosure, respectively, and found that the benefits and the risks did not function independently but interdependently, and the justice would play a crucial role when both the benefits and the risks were high. Furthermore, the authors found that there were asymmetric mechanisms for high disclosure and low disclosure, and males focused more on perceived usefulness, while females concerned more about perceived enjoyment, privacy risks and perceived justice.Originality/valueThis paper further extends privacy calculus model (PCM) and deepens the understanding of the privacy calculus process from a configurational perspective. In addition, this study also provides guidance for future research on how to adopt the configurational approach with qualitative comparative analysis (QCA) to revise and improve relevant theories for information systems (IS) behavioral research.
Does governance quality matter in the nexus of inclusive finance and stability?
Authors: Saha Mallika , Dutta Kumar Debasis 
Published: January 2022

PurposeDespite numerous evidence of policy trade-off in financial inclusion-stability nexus, little is known about the role of governance quality to align policy goals and maximizing the social benefits. Therefore, to fill the gap, this study focuses to investigate the moderating effect of country governance (CG) in the interplay between financial-inclusion (FI) and financial-stability (FS), using a large panel of 84 economies covering the years 2004–2017.Design/methodology/approachFor attaining this objective, the study constructs several indexes for FI, FS and CG using principal component analysis (PCA) and examines how FI influences FS at different CG levels applying advanced econometrics. FindingsThe results show that CG plays a very crucial role in eradicating the trade-off and strengthens the synergy between FI and FS. The findings are insensitive to several robustness validations and could be constructive for policymakers to devise policies and to ensure financial stability.Originality/valueAs far as the authors are aware, this is the only paper that empirically explains CG's role in FI-FS nexus.
Shake it off and eat less: anxiety-inducing product packaging design influences food product interaction and eating
Authors: Ilicic Jasmina , Brennan Stacey M. 
Published: January 2022

Purpose
This research aims to introduce an anxious product-shaking effect, whereby consumers regulate the emotion of anxiety (i.e. anxious, nervous and jittery) elicited through product packaging design by shaking a product, which decreases eating intentions and behavior. Shaking product interaction as a result of anxiety-inducing product packaging design is introduced as a strategy to counter emotional eating, as an effective preventive measure of obesity.

Design/methodology/approach
Three laboratory studies (Studies 1–3) and one online study (Study 4) are conducted. Study 1 examines the effect of anxiety-inducing product packaging design on product interaction (i.e. shaking vs pouring). Study 2 investigates whether product shaking is a form of emotional regulation to anxiety-inducing product packaging design. Study 3 explores the effect of emotional regulation suppression (i.e. pouring) and facilitation (i.e. shaking) on eating behavior. Study 4 examines the moderating role of phobia severity on the effect of anxiety-inducing product packaging on emotional regulation and the downstream consequences on eating intentions.

Findings
Results demonstrate that the presence of anxiety-eliciting product packaging design results in shaking of the product (Study 1) as a form of emotional regulation (Study 2). Results from Study 3 find that emotional regulation facilitation (i.e. shaking) decreases eating, while emotion regulation suppression (i.e. pouring) increases eating. Results of Study 4 show that when exposed to anxiety-inducing product packing design, those with low phobia severity are less likely to regulate their emotions, which subsequently increases their eating intentions.

Research limitations/implications
This research is limited as it focuses only on product interaction and consumption of food products.

Practical implications
This research has important implications for marketers and product managers, as well as public policymakers, in encouraging responsible consumption behaviors in consumers. Marketing, product managers and policymakers should consider packaging design to introduce anxiety-inducing imagery on the packaging itself as a way to encourage shaking emotional regulation and to reduce eating, especially of unhealthy foods such as confectionary.

Originality/value
This research introduces and provides evidence of an anxious product-shaking effect that can reduce consumption of unhealthy food products. Anxiety-inducing packaging design strategy results in the emotional regulation of product shaking, which can reduce eating intentions and behavior.
Perceptions of face threats in conflict
Authors: Donohue William A. , Druckman Daniel 
Published: January 2022

Purpose
The purpose of this study was to determine the relative impact of positive and negative face threats in conflict scenarios on the relational quality between disputants. This study also sought to determine whether the contextual variables of relational distance and power differential mediated this relationship as predicted by politeness theory.

Design/methodology/approach
To test the hypotheses, a 2 × 2 × 2 design was implemented manipulating the variables face (positive and negative), relational distance (business and personal) and power differential (high and low power differential). Participants read one of the eight scenarios, then responded to the dependent variables which focused on the impact of the face threats on relational quality between the participants. Subjects were recruited using the M-Turk, Amazon platform. Manipulation checks were carefully constructed to ensure subjects understood them.

Findings
The results of this study indicated that positive face threats have significantly more impact on relational quality between disputants than negative face threats. Moreover, context did not mediate these results. Neither relational distance nor power differential impacted the extent to which positive face threats compromised the relationship between the disputants.

Research limitations/implications
This is the first study to explore the impact of face threats on relational outcomes in conflict. Prior studies focused only on the extent to which contextual variables would impact the choice of face threats that disputants might make in response to power and relational distance differences. This result suggests that face threats play a significant role in determining relational outcomes in conflict settings.

Practical implications
This study suggests that practitioners, such as mediators or group facilitators, should take steps to limit the kinds of positive face threats that disputants exchange during conflict. If positive face threats are allowed to escalate, then they can severely compromise the willingness of disputants to trust and continue to work toward an integrative solution.

Social implications
Political divisions often appear to widen in the context of positive face threats as individuals seek to belittle the identities of their opponents. As these face threats escalate, they can result in polarizing language that disempowers these individuals from wanting to work together in a trusting relationship to accomplish important social goals.

Originality/value
This is the first study to explore the relative impact of positive and negative face threats on the relational quality of disputants in conflict. It is also the first to explore the extent to which context mediates the impact of face threats.