bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gambling on an empty stomach: Hunger modulates preferences for learned but not described risks
Authors: van Swieten Maaike M.H. , Bogacz Rafal , Manohar Sanjay G. 
Published: March 2021

AbstractWe assess risks differently when they are explicitly described, compared to when we learn directly from experience, suggesting dissociable decision-making systems. Our needs, such as hunger, could globally affect our risk preferences, but do they affect described and learned risks equally? On one hand, explicit decision-making is often considered flexible and contextsensitive, and might therefore be modulated by metabolic needs. On the other hand, implicit preferences learned through reinforcement might be more strongly coupled to biological drives. To answer this, we asked participants to choose between two options with different risks, where the probabilities of monetary outcomes were either described or learned. In agreement with previous studies, rewarding contexts induced risk-aversion when risks were explicitly described, but risk-seeking when they were learned through experience. Crucially, hunger attenuated these contextual biases, but only for learned risks. The results suggest that our metabolic state determines risk-taking biases when we lack explicit descriptions.
Human gaze is systematically offset from the center of cone topography
Authors: Reiniger Jenny L. , Domdei Niklas , Holz Frank G. , Harmening Wolf M. 
Published: March 2021

SummaryThe small physical depression of the human retina, the fovea, is the retinal locus of prime visual resolution, achieved by a peaking topography of the light sensitive cone photoreceptor outer segments1–3and a post-receptor wiring scheme preserving high-density sampling4,5. Humans dynamically direct their gaze such that the retinal images of objects of interest fall onto the foveola, the central one-degree diameter of the fovea6–8, but it is yet unclear if a relationship between the individual photoreceptor topography at this location and visual fixation behavior exists9,10. By employing adaptive optics in vivo imaging and micro-stimulation11–13, we created topographical maps of the complete foveolar cone mosaics in both eyes of 20 healthy participants while simultaneously recording the retinal location of a fixated visual object in a psychophysical experiment with cellular resolution. We found that the locus of fixation was systematically shifted away from the topographical centers towards a naso-superior quadrant on the retina, about 5 minutes of arc of visual angle on average, with a mirror symmetrical trend between fellow eyes. In cyclopean view, the topographical centers were superior to the fixated target, corresponding to areas in the visual field usually more distant14,15and thus containing higher spatial frequencies. Given the large variability in foveal topography between individuals, and the surprising precision with which fixation is repeatedly directed to just a small bouquet of cones in the foveola, these findings demonstrate a finely tuned, functionally relevant link between the development of the cellular mosaic of photoreceptors and visual behavior.
Molecular features of RNA silencing against phloem-restricted polerovirus TuYV enable amplification of silencing signal from host transcripts
Authors: Clavel Marion , Lechner Esther , Incarbone Marco , Vincent Timothée , Cognat Valerie , Smirnova Ekaterina , Lecorbeiller Maxime , Brault Véronique , Ziegler-Graff Véronique , Genschik Pascal 
Published: March 2021

AbstractIn plants and some animal lineages, RNA silencing is an efficient and adaptable defense mechanism against viruses. To counter it, viruses encode suppressor proteins that interfere with RNA silencing. Phloem-restricted viruses are spreading at an alarming rate and cause substantial reduction of crop yield, but how they interact with their hosts at the molecular level is still insufficiently understood. Here, we investigate the antiviral response against phloem-restricted turnip yellows virus (TuYV) in the model plantArabidopsis thaliana. Using a combination of genetics, deep sequencing, and mechanical vasculature enrichment, we show that the main axis of silencing active against TuYV involves 22-nt vsiRNA production by DCL2, and their preferential loading into AGO1. Unexpectedly, and despite the viral encoded VSR P0 previously shown to mediate degradation of AGO proteins, vascular AGO1 undergoes specific post-translational stabilization during TuYV infection. We also identify vascular novel secondary siRNA produced from conserved plant transcripts and initiated by DCL2-processed AGO1-loaded vsiRNA, supporting a viral strategy to modulate host response. Collectively, our work uncovers the complexity of antiviral RNA silencing against phloem-restricted TuYV and prompts a re-assessment of the role of its suppressor of silencing P0 during genuine infection.
UNC-45A is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System
Authors: Clemente Valentino , Hoshino Asumi , Meints Joyce , Shetty Mihir , Starr Tim , Lee Michael , Bazzaro Martina 
Published: March 2021

AbstractUNC-45A is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the acto-myosin system and as a Microtubule (MT)-destabilizing protein. UNC-45A is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug Paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment in highly proliferating and prone to remodeling cells and in microtubule-rich areas of in the ovaries and in neurons respectively. In both apparatuses UNC-45A is also abundantly expressed in the ciliated epithelium. Because regulators of acto-myosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development and in neurodegeneration.
CSF1R inhibitor levels determine sex-specific phenotype of resilient microglia and neurofunctional rescue leading to extended survival in tauopathy mice
Authors: Johnson Noah R. , Yuan Peng , Castillo Erika , Lopez T. Peter , Yue Weizhou , Bond Annalise , Rivera Brianna M. , Sullivan Miranda C. , Hirouchi Masakazu , Giles Kurt , Aoyagi Atsushi , Condello Carlo 
Published: March 2021

ABSTRACTMicroglia are central to pathogenesis in many neurological conditions. Drugs targeting colony- stimulating factor-1 receptor (CSF1R) to block microglial proliferation in preclinical disease models have shown mixed outcomes, thus the therapeutic potential of this approach remains unclear. Here, CSF1R inhibitors were evaluated in tauopathy mice using multiple dosing schemes, drug analogs, and longitudinal measurements in the brain and plasma. A sex- independent reduction in pathogenic tau was seen in several models and non-microglial gene expression patterns reverted toward a normal wild type signature. Surprisingly, despite greater drug exposure in male mice, functional rescue and extended survival was only observed in female mice. A dose-dependent upregulation of immediate early genes and neurotransmitter dysregulation were observed in the brains of male mice only, indicating that excitotoxicity may have precluded functional benefits. Drug-resilient microglia in male mice exhibited morphological and gene expression patterns consistent with increased neuroinflammatory signaling, suggesting a mechanistic basis for sex-specific excitotoxicity. These data argue that complete microglial ablation is neither required nor desirable for neuroprotection and that therapeutics targeting microglia must consider sex-dependent effects on functional outcomes.
Factors informing healthcare workers’ willingness to work during the COVID-19 pandemic
Authors: Malesza Marta 
Published: March 2021

AbstractObjectiveThe COVID-19 pandemic represents a substantial challenge to healthcare workers. Exploring the determinants of their willingness to work is crucial to ensuring hospital function during the outbreak. Hence, this study examines the factors affecting the motivation and hesitation of health workers in the face of the COVID-19 pandemic in Poland.Study DesignAn online, anonymous survey was carried out among Polish healthcare workers during the COVID-19 pandemic.MethodThe respondents were asked about their demographic characteristics, stress-related factors, and their self-reported motivation and hesitation to work. The responses were gathered during September-December 2020.Results912 valid responses were obtained. Of these, 22.8% (N = 208) respondents reported being strongly motivated to work while 37.8% (N = 345) expressed strong hesitation. The participants’ demographic characteristics and their responses to the stress-related questions were assigned to four categories depending on the odds ratios of motivation and hesitation. While some factors were linked to enhanced motivation and reduced hesitation, others solely affected either motivation or hesitation, and yet others had a positive impact on both.ConclusionOverall, the study indicates that in order to increase hospital workers’ motivation and decrease their hesitation, they must be made to feel protected by both their hospitals and local and national authorities.
Fusion of the N-terminal 119 amino acids with the RelA-CTD renders its growth inhibitory effects ppGpp-dependent
Authors: Tailor Krishma , Sagar Prarthi , Dave Keyur , Pohnerkar Jayashree 
Published: March 2021

AbstractThe guanosine nucleotide derivatives ppGpp and pppGpp, are central to the remarkable capacity of bacteria to adapt to fluctuating environment and metabolic perturbations. These alarmones are synthesized by two proteins, RelA and SpoT inE. coliand the activities of each of the two enzymes are highly regulated for homeostatic control of (p)ppGpp levels in the cell. Although the domain structure and function of RelA are well defined, the findings of this study unfold the regulatory aspect of RelA that is possibly relevantin vivo. We uncover here the importance of the N-terminal 1-119 amino acids of the enzymatically compromised (p)ppGpp hydrolytic domain (HD) of monofunctional RelA for the (p)ppGpp mediated regulation of RelA-CTD function. We find that even moderate level expression of RelA appreciably reduces growth when the basal levels of (p)ppGpp in the cells are higher than in the wild type, an effect independent of its ability to synthesize (p)ppGpp. This is evidenced by the growth inhibitory effects of oversynthesis of the RelA-CTD in therelA+strain but not inrelAnull mutant, suggesting the requirement of the functional RelA protein for basal level synthesis of (p)ppGpp, accordingly corroborated by the restoration of the growth inhibitory effects of the RelA-CTD expression in therelA1 spoT202mutant. The N-terminal 119 amino acids of RelA fused in-frame with the RelA-CTD, both from 406-744 amino acids (including TGS) and from 454-744 amino acids (sans TGS) caused growth inhibition only inspoT1andspoT202 relA1mutants, uncovering the hitherto unrealized (p)ppGpp-dependent regulation of RelA-CTD function. An incremental rise in the (p)ppGpp levels is proposed to progressively modulate the interaction of RelA-CTD with the ribosomes, with possible implications in the feedback regulation of the N-terminal (p)ppGpp synthesis function, a proposal that best explains the nonlinear relationship between (p)ppGpp synthesis and increased ratio of RelA:ribosomes, bothin vitroas well asin vivo.
Comparative repeat profiling of two closely related conifers (Larix decidua and Larix kaempferi) reveals high genome similarity with only few fast-evolving satellite DNAs
Authors: Heitkam Tony , Schulte Luise , Weber Beatrice , Liedtke Susan , Breitenbach Sarah , Kögler Anja , Morgenstern Kristin , Brückner Marie , Tröber Ute , Wolf Heino , Krabel Doris , Schmidt Thomas 
Published: March 2021

ABSTRACTIn eukaryotic genomes, cycles of repeat expansion and removal lead to large-scale genomic changes and propel organisms forward in evolution. However, in conifers, active repeat removal is thought to be limited, leading to expansions of their genomes, mostly exceeding 10 gigabasepairs. As a result, conifer genomes are largely littered with fragmented and decayed repeats. Here, we aim to investigate how the repeat landscapes of two related conifers have diverged, given the conifers’ accumulative genome evolution mode. For this, we applied low coverage sequencing and read clustering to the genomes of European and Japanese larch,Larix decidua(Lamb.) Carrière andLarix kaempferi(Mill.), that arose from a common ancestor, but are now geographically isolated. We found that bothLarixspecies harbored largely similar repeat landscapes, especially regarding the transposable element content. To pin down possible genomic changes, we focused on the repeat class with the fastest sequence turnover: satellite DNAs (satDNAs). Using comparative bioinformatics, Southern, and fluorescentin situhybridization, we reveal the satDNAs’ organizational patterns, their abundances, and chromosomal locations. Four out of the five identified satDNAs are widespread in theLarixgenus, with two even present in the more distantly relatedPseudotsugaandAbiesgenera. Unexpectedly, the EulaSat3 family was restricted toL. deciduaand absent fromL. kaempferi, indicating its evolutionarily young age. Taken together, our results exemplify how the accumulative genome evolution of conifers may limit the overall divergence of repeats after speciation, producing only few repeat-induced genomic novelties.
Two interacting transcriptional coactivators cooperatively control plant immune responses
Authors: Chen Huan , Li Min , Qi Guang , Zhao Ming , Liu Longyu , Zhang Jingyi , Chen Gongyou , Wang Daowen , Liu Fengquan , Fu Zheng Qing 
Published: March 2021

AbstractThe phytohormone salicylic acid (SA) plays a pivotal role in plant defense against biotrophic and hemibiotrophic pathogens. Genetic studies have identified NPR1 and EDS1 as two central hubs in plant local and systemic immunity. However, it is unclear how NPR1 orchestrates gene regulation and whether EDS1 directly participates in transcriptional reprogramming. Here we show that NPR1 and EDS1 synergistically activatePathogenesis-Related(PR) genes and plant defenses by forming a protein complex and co-opting with Mediator. In particular, we discover that EDS1 functions as an autonomous transcriptional coactivator with intrinsic transactivation domains and physically interacts with the CDK8 subunit of Mediator. Upon SA induction, EDS1 is directly recruited by NPR1 onto thePR1promoter via physical NPR1-EDS1 interactions, thereby potentiatingPR1activation. We further demonstrate that EDS1 stabilizes NPR1 protein and NPR1 transcriptionally upregulatesEDS1in plant-pathogen interactions. Our results reveal an elegant interplay of key coactivators with Mediator and elucidate novel molecular mechanisms for activating transcription during immune responses.
Identifying Differential Methylation in Cancer Epigenetics via a Bayesian Functional Regression Model
Authors: Shokoohi Farhad , Stephens David A. , Greenwood Celia M.T. 
Published: March 2021

AbstractDNA methylation plays an essential role in regulating gene activity, modulating disease risk, and determining treatment response. Researchers can obtain insight into methylation patterns at a single nucleotide level utilizing next-generation sequencing technologies. However, complex features inherent in the data obtained via these technologies pose challenges beyond the typical big data problems. Identifying differentially methylated cytosines (dmc) or regions is one of such challenges. Current methodologies for identifying dmcs fall short in handling low read-depth data and missing values, capturing functional data patterns, granting multiple covariates (categorical, continuous, or combination), and multiple group comparisons. We have developed an efficient method to identify dmcs based on a Bayesian functional regression approach, termedDMCFB, that tackles these shortcomings. Through simulation studies, we establish thatDMCFBoutperforms current methods and results in better smoothing, and efficient imputation. We apply the proposed method to analyze a dataset containing patients with acute promyelocytic leukemia and control samples. WithDMCFB, we discovered many new dmcs, and more importantly, exhibited enhanced consistency of differential methylation within islands and at their adjacent shores. Furthermore, we detected differential methylation at more of the binding sites of the fused gene involved in this cancer.
A novel method for generating 3D constructs with branched vascular networks using multi-materials bioprinting and direct surgical anastomosis
Authors: Liu Xin , Wang Xinhuan , Zhang Liming , Sun Lulu , Wang Heran , Zhao Hao , Zhang Zhengtao , Huang Yiming , Zhang Jingjinqiu , Song Biaobiao , Li Chun , Zhang Hui , Li Song , Wang Shu , Zheng Xiongfei , Gu Qi 
Published: March 2021

AbstractVessels pervade almost all body tissues, and significantly influence the pathophysiology of human body. Previous attempts to establish multi-scale vascular connection and function in 3D model tissues using bioprinting have had limited success due to the incoordination between cell-laden materials and stability of the perfusion channel. Here, we report a methodology to fabricate centimetre-scale vascularized soft tissue with high viability and accuracy using multi-materials bioprinting involving inks with low viscosity and a customized multistage-temperature-control printer. The tissue formed was perfused with branched vasculature with well-formed 3D capillary network and lumen, which would potentially supply the cellular components with sufficient nutrients in the matrix. Furthermore, the same methodology was applied for generating liver-like tissue with the objective to fabricate and mimic a mature and functional liver tissue, with increased functionality in terms of synthesis of liver specific proteins afterin vitroperfusion andin vivosubperitoneal transplantation in mice. Moreover, to establish immediate blood perfusion, an elastic layer was printed wrapping sacrificial ink to support the direct surgical anastomosis of the carotid artery to the jugular vein. Our findings highlight the support extended by vasculature network in soft hydrogels which helps to sustain the thick and dense cellularization in engineered tissues.
Neural Representation of the Relational Self from Infancy to Adulthood
Authors: Ulmer-Yaniv Adi , Waidergoren Shani , Shaked Ariel , Salomon Roy , Feldman Ruth 
Published: March 2021

AbstractInvestigations into the neural underpinnings of the “self” highlight its complexity and multi-dimensionality and emphasize that various aspects of the self are sustained by different neural systems. Here, we focused on the Relational Self, a dimension denoting the self-within-attachment-relationships that taps the continuity of attachment across individual development and affiliative bonds. Mothers and children were followed across two decades and videotaped in naturalistic interactions at three ages: infancy (3-6 months), childhood (9-12 years), and young adulthood (18-24 years). During fMRI scanning, young adults were exposed to videos of their own mother-child interactions from the three ages versus matched unfamiliar interactions. Relational Self-stimuli elicited greater activations across preregistered nodes of the human caregiving network, including thalamus-to-brainstem, amygdala, hippocampus, ACC, insula, and temporal cortex. Critically, Relational Self-stimuli were age-invariant in most regions of interest despite large variability of stimuli across multiple self-related features, such as similarity, temporal distance, affect, or mentalization, and Bayesian analysis indicated strong evidence for lack of age-related differences. PPI analysis demonstrated that Relational Self-stimuli elicited tighter connectivity between the ACC and insula. Greater child social engagement during interaction with mother correlated with higher ACC and insula response to Relational Self-stimuli. Findings highlight an important novel dimension in the neural representation of the self, suggest that the Relational Self may be sustained by a paralimbic interface integrating exteroceptive and interoceptive self-related signals, and demonstrate overlap in the attachment network of parents and children, lending support to perspectives on the continuity of attachment and self across the individual’s developmental history.Significance StatementDescribing the neural underpinnings of the “self” is inherently complex due to the multi-dimensionality of the construct. Following mothers and children from infancy to adulthood, we focused on the Relational Self, a dimension denoting the self-within-attachment-relationships, and exposed young adults to own versus unfamiliar mother-child interactions across their relational history. Relational Self stimuli triggered greater activations in the human caregiving network, including thalamus-to-brainstem, amygdala, hippocampus, ACC, insula, and temporal cortex, were age-invariant, and elicited tighter connectivity between ACC and insula, creating a paralimbic interface of interoception-exteroception sustaining the Relational Self. Findings highlight a novel dimension in the neural representation of the self and lend support to perspectives emphasizing the cross-generational transmission of attachment and its continuity across the individual’s developmental history.
Identification of regulatory networks associated with anti-HIV/AIDS genes via integrated transcriptome, epigenome and proteome analyses
Authors: Liu Gexin , Zhang Chunlin , Shi Lei , Zhu Zhenglin 
Published: March 2021

AbstractThere are individuals naturally resistant to HIV. To identify anti-HIV genes and regulatory networks that enable the native ability to resist HIV, we reanalyzed the transcriptome of HIV resistant and susceptible individuals based on previous efforts, and performed regulatory network prediction using HIV-infection related DNA methylation, miRNA and Chip-SEQ data. We totally found 25 potential anti-HIV genes and 23 of them are newly identified. They are enriched in pathways of immunity, neurological system and cell signaling. 4 anti-HIV genes show DNA hypermethylation signatures and 4 are possibly bounded by the HIV-1 Trans-Activator of Transcription protein (Tat). We found a potential HIV-resistance correlated miRNA hsa-miR-3074-5p possibly regulating an anti-HIV hub gene JUN. Our findings provide novel insights for AIDS treatments and approaches to HIV vaccine design.