bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust transcriptional profiling and identification of differentially expressed genes with low input RNA sequencing of adult hippocampal neural stem and progenitor populations
Authors: Denninger Jiyeon K. , Walker Logan A. , Chen Xi , Turkoglu Altan , Pan Alex , Tapp Zoe , Senthilvelan Sakthi , Rindani Raina , Kokiko-Cochran Olga , Bundschuh Ralf , Yan Pearlly , Kirby Elizabeth D. 
Published: November 2021

AbstractMultipotent neural stem cells (NSCs) are found in several isolated niches of the adult mammalian brain where they have unique potential to assist in tissue repair. Modern transcriptomics offer high-throughput methods for identifying disease or injury associated gene expression signatures in endogenous adult NSCs, but they require adaptation to accommodate the rarity of NSCs. Bulk RNA sequencing (RNAseq) of NSCs requires pooling several mice, which impedes application to labor-intensive injury models. Alternatively, single cell RNAseq can profile hundreds to thousands of cells from a single mouse and is increasingly used to study NSCs. The consequences of the low RNA input from a single NSC on downstream identification of differentially expressed genes (DEGs) remains largely unexplored. Here, to clarify the role that low RNA input plays in NSC DEG identification, we directly compared DEGs in an oxidative stress model of cultured NSCs by bulk and single cell sequencing. While both methods yielded DEGs that were replicable, single cell sequencing DEGs derived from genes with higher relative transcript counts compared to all detected genes and exhibited smaller fold changes than DEGs identified by bulk RNAseq. The loss of high fold-change DEGs in the single cell platform presents an important limitation for identifying disease-relevant genes. To facilitate identification of such genes, we determined an RNA-input threshold that enables transcriptional profiling of NSCs comparable to standard bulk sequencing and used it to establish a workflow for in vivo profiling of endogenous NSCs. We then applied this workflow to identify DEGs after lateral fluid percussion injury, a labor-intensive animal model of traumatic brain injury. Our work suggests that single cell RNA sequencing may underestimate the diversity of pathologic DEGs but population level transcriptomic analysis can be adapted to capture more of these DEGs with similar efficacy and diversity as standard bulk sequencing. Together, our data and workflow will be useful for investigators interested in understanding and manipulating adult hippocampal NSC responses to various stimuli.
Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons
Authors: Printz Yoav , Patil Pritish , Mahn Mathias , Benjamin Asaf , Litvin Anna , Levy Rivka , Bringmann Max , Yizhar Ofer 
Published: November 2021

AbstractThe medial prefrontal cortex (mPFC) mediates a variety of complex cognitive functions via its vast and diverse connections with cortical and subcortical structures. Understanding the patterns of synaptic connectivity that comprise the mPFC local network is crucial for deciphering how this circuit processes information and relays it to downstream structures. To elucidate the synaptic organization of the mPFC, we developed a high-throughput optogenetic method for mapping large-scale functional synaptic connectivity. We show that mPFC neurons that project to the basolateral amygdala display unique spatial patterns of local-circuit synaptic connectivity within the mPFC, which distinguish them from the general mPFC cell population. Moreover, the intrinsic properties of the postsynaptic mPFC cell and anatomical position of both cells jointly account for ~7.5% of the variation in probability of connection between mPFC neurons, with anatomical distance and laminar position explaining most of this fraction in variation. Our findings demonstrate a functional segregation of mPFC excitatory neuron subnetworks, and reveal the factors determining connectivity in the mPFC.
Nuclear mRNA metabolism drives selective basket assembly on a subset of nuclear pores in budding yeast
Authors: Bensidoun Pierre , Reiter Taylor , Montpetit Ben , Zenklusen Daniel , Oeffinger Marlene 
Published: November 2021

ABSTRACTTo determine which transcripts should reach the cytoplasm for translation, eukaryotic cells have established mechanisms to regulate selective mRNA export through the nuclear pore complex (NPC). The nuclear basket, a substructure of the NPC protruding into the nucleoplasm, is thought to function as a stable platform where mRNA-protein complexes (mRNPs) are rearranged and undergo quality control (QC) prior to export, ensuring that only mature mRNAs reach the cytoplasm. Here, we use proteomic, genetic, live-cell, and single-molecule resolution microscopy approaches in budding yeast to demonstrate that baskets assemble only on a subset of NPCs and that basket formation is dependent on RNA polymerase II (Pol II) transcription and subsequent mRNP processing. Specifically, we observe that the cleavage and polyadenylation machinery, the poly(A)-binding protein Pab1, and pre-mRNA-leakage factor Pml39 are required for basket assembly. We further show that while all nuclear pores can bind Mlp1, baskets assemble only on a subset of nucleoplasmic NPCs, and these basket-containing pores associate a distinct protein and RNA interactome. Taken together, our data points towards nuclear pore heterogeneity and an RNA-dependent mechanism for functionalization of nuclear pores in budding yeast through nuclear basket assembly.
Genotype-phenotype correlation analysis and therapeutic development using a patient stem cell-derived disease model of Wolfram syndrome
Authors: Kitamura Rie Asada , Maxwell Kristina G. , Ye Wenjuan , Kries Kelly , Brown Cris M , Augsornworawat Punn , Hirsch Yoel , Johansson Martin M , Weiden Tzvi , Ekstein Joseph , Cohen Joshua , Klee Justin , Leslie Kent , Simeonov Anton , Henderson Mark J. , Millman Jeffrey R. , Urano Fumihiko 
Published: November 2021

AbstractWolfram syndrome is a rare genetic disorder largely caused by pathogenic variants in the WFS1 gene and manifested by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Recent genetic and clinical findings have revealed Wolfram syndrome as a spectrum disorder. Therefore, a genotype-phenotype correlation analysis is needed for diagnosis and therapeutic development. Here, we focus on the WFS1 c.1672C>T, p.R558C variant which is highly prevalent in the Ashkenazi-Jewish population. Clinical investigation indicates that subjects carrying the homozygous WFS1 c.1672C>T, p.R558C variant show mild forms of Wolfram syndrome phenotypes. Expression of WFS1 p.R558C is more stable compared to the other known recessive pathogenic variants associated with Wolfram syndrome. Stem cell-derived islets (SC-islets) homozygous for WFS1 c.1672C>T variant recapitulates genotype-related Wolfram phenotypes, which are milder than those of SC-islets with compound heterozygous WFS1 c.1672C>T (p.R558C), c.2654C>T (p.P885L). Enhancing residual WFS1 function by a combination treatment of chemical chaperones, sodium 4-phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), mitigates detrimental effects caused by the WFS1 c.1672C>T, p.R558C variant and restored SC-islet function. Thus, the WFS1 c.1672C>T, p.R558C variant causes a mild form of Wolfram syndrome phenotypes, which can be remitted with a combination treatment of chemical chaperones. We demonstrate that our patient stem cell-derived disease model provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.One sentence summaryDevelopment of personalized therapy for Wolfram syndrome using genetics and iPSC model.
Moth species richness in an upland tropical rainforest: A citizen scientist assisted study
Authors: Tng David Y. P. , Apgaua Deborah M. G. , Fisher Nicholas J. , Fazio Victor W. 
Published: November 2021

AbstractDiversity studies on moths in Australia are rare, presenting various shortfalls in knowledge that impedes and understanding of their biodiversity values and their conservation. In particular, the Wet Tropics of Australia deserves attention, given the paucity of systematic moth surveys in the region and its World Heritage Area status. To fill this knowledge gap, we conducted a study to observe moths on 191 nights over a main one-year survey period at an upland rainforest locality, and uploaded all observations on iNaturalist. We also compiled other incidental observations in the general locality by other observers and observations outside the survey period. In total, we document 4,434 observations of moths represented by 1041 distinct moth morphospecies. Of these, 703 are formally named species of moths, 146 to genus and 255 to higher taxonomic designations above genus level. Despite the rather intensive main survey effort, our results suggest that we have yet to reach a plateau in documenting the moth species richness of the locality. Using this study as a model, we show that the iNaturalist platform serves as an effective means to document and digitally curate biodiversity values at a locality, whilst providing complete data transparency and enabling broader community engagement of citizen scientists. We recommend the use of iNaturalist for future moth inventories, and as a resource for follow up meta-analyses of regional moth diversity and distributions.
Sincast: a computational framework to predict cell identities in single cell transcriptomes using bulk atlases as references
Authors: Deng Yidi , Choi Jarny , Lê Cao Kim-Anh 
Published: November 2021

AbstractCharacterizing the molecular identity of a cell is an essential step in single cell RNA-sequencing (scRNA-seq) data analysis. Numerous tools exist for predicting cell identity using single cell reference atlases. However, many challenges remain, including correcting for inherent batch effects between reference and query data and insufficient phenotype data from the reference. One solution is to project single cell data onto established bulk reference atlases to leverage their rich phenotype information.Sincast is a computational framework to query scRNA-seq data based on bulk reference atlases. Prior to projection, single cell data are transformed to be directly comparable to bulk data, either with pseudo-bulk aggregation or graph-based imputation to address sparse single cell expression profiles. Sincast avoids batch effect correction, and cell identity is predicted along a continuum to highlight new cell states not found in the reference atlas.In several case study scenarios, we show that Sincast projects single cells into the correct biological niches in the expression space of the bulk reference atlas. We demonstrate the effectiveness of our imputation approach that was specifically developed for querying scRNA-seq data based on bulk reference atlases. We show that Sincast is an efficient and powerful tool for single cell profiling that will facilitate downstream analysis of scRNA-seq data.
Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease
Authors: Keshvari Sahar , Genz Berit , Teakle Ngari , Caruso Melanie , Cestari Michelle F. , Patkar Omkar L. , Tse Brian WC , Sokolowski Kamil A , Ebersbach Hilmar , Jascur Julia , MacDonald Kelli P. A. , Miller Gregory , Ramm Grant A. , Pettit Allison R. , Clouston Andrew D. , Powell Elizabeth E. , Hume David A. , Irvine Katharine M. 
Published: November 2021

AbstractResident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, utilizing a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodeling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.Summary statementMacrophages contribute to both progression and resolution of chronic tissue injury and fibrogenesis. Administration of a macrophage growth factor promoted liver regeneration and resolution of advanced liver fibrosis in mice.
MAP4K3 inhibits Sirtuin-1 to repress the LKB1-AMPK pathway to promote amino acid dependent activation of the mTORC1 complex
Authors: Branch Mary Rose , Hsu Cynthia L. , Ohnishi Kohta , Lee Elian , Meisenhelder Jill , Winborn Brett , Sopher Bryce L. , Taylor J. Paul , Hunter Tony , La Spada Albert R. 
Published: November 2021

AbstractmTORC1 is the key rheostat controlling cellular metabolic state. Of the various inputs to mTORC1, the most potent effector of intracellular nutrient status is amino acid supply. Despite an established role for MAP4K3 in promoting mTORC1 activation in the presence of amino acids, the signaling pathway by which MAP4K3 controls mTORC1 activation remains unknown. Here we examined the process of MAP4K3 activation of mTORC1 and found that MAP4K3 represses the LKB1-AMPK pathway to prevent TSC1/2 complex inactivation of Rheb. When we sought the regulatory link between MAP4K3 and LKB1 inhibition, we discovered that MAP4K3 physically interacts with the master nutrient regulatory factor Sirtuin-1 and phosphorylates Sirtuin-1 to repress LKB1 activation. Our results reveal the existence of a novel signaling pathway linking amino acid satiety with MAP4K3-dependent suppression of SIRT1 to inactivate the repressive LKB1-AMPK pathway and thereby potently activate the mTORC1 complex to dictate the metabolic disposition of the cell.
The role of regulatory focus and team mindfulness in megaproject conflicts
Authors: Wang Dedong , Wang Yuxue 
Published: November 2021

PurposeProject conflicts are inevitable. Megaproject conflicts need to be managed across different levels. The purpose of this study is to investigate the role of individual-level regulatory focus and organization-level team mindfulness in managing megaproject conflicts.Design/methodology/approachBy combining the individual motivation basis and organizational background of conflict resolution, this study constructed a multi-level structural equation model. The hypothesis is tested based on data collected from 182 respondents.FindingsThe findings of this study show that project manager's promotion focus has a direct positive effect on task conflict and a negative effect on relationship conflict. Prevention focus has a positive effect on relationship conflict and a negative effect on task conflict and process conflict. Team mindfulness has a negative effect on relationship conflict and process conflict and a positive effect on task conflict. Task conflict was negatively affected by the interaction between team mindfulness and promotion focus. The interaction between team mindfulness and prevention focus had a positive effect on relationship conflict.Originality/valueThis study verifies the positive role of project manager's promotion focus and prevention focus in conflict management and clarifies the strengthening role of team mindfulness in constructive conflict and the prevention role in destructive conflict. This study also confirms that team mindfulness can act as a reinforcement and complementary factor of regulatory focus in megaproject conflict, contributing to the current understanding of the project manager's role in megaproject mindfulness contexts.
Regulating non-financial reporting: evidence from European firms’ environmental, social and governance disclosures and earnings risk
Authors: Arif Muhammad , Gan Christohper , Nadeem Muhammad 
Published: November 2021

PurposeMotivated by the enactment of non-financial reporting regulations by the European Parliament, this paper aims to investigate the impact of European Union (EU) directive 2014/95/EU on the quantity of environmental, social and governance (ESG) disclosures by the S&P Europe 350 index firms. This study also investigates whether the implementation of the non-financial information (NFI) reporting regulations influences the association between ESG disclosures and firms’ earnings risk.Design/methodology/approachTo measure the impact of mandatory regulations on the quantity of ESG disclosures, this study estimates the average treatment effects using a propensity weighted sample. Then this study uses the difference-in-differences method to estimate the differences in the association between ESG disclosures and earning risk before and after implementation of the EU directive.FindingsThe results show a significant positive impact of the EU directive on the quantity of ESG disclosures for the sample European public-interest entities, which indicates that the mandatory NFI reporting requirements could boost the availability of increasingly demanded ESG related information. The enhanced association between the ESG disclosures and firms’ earnings risk during the post-directive period reveals that mandating NFI reporting also increases the quality of ESG disclosures.Originality/valueUsing the legitimacy and decision-usefulness theories, this study provides novel evidence concerning the impact of the EU directive on the quantity and quality of ESG disclosures.
When consumers touch: a conceptual model of consumer haptic perception
Authors: Ranaweera Achini Tharaka 
Published: November 2021

Purpose
Touch plays an important role in the evaluations of products. However, prior quantitative touch research does not present a holistic perspective of haptics. This study aims to provide a more comprehensive understanding of haptic information that consumers attain from touch.

Design/methodology/approach
Adopting a qualitative research approach, semi-structured, depth interviews were conducted with industry experts.

Findings
Based on the findings, this research proposes a conceptual model of consumer haptic perception consisting of seven key influences, namely, the effects of haptic sensation, haptic perception, the influence of individual factors, the influence of external environmental factors, the multi-dimensionality of haptics, haptic cue congruity and haptic dominance.

Practical implications
This study suggests firms to understand the importance of consumers’ haptic perception as an opportunity to engage an individual’s heart and mind through information attained through touch.

Originality/value
This is the first study in marketing to propose a conceptual model of haptics comprising several new haptic influences. This model contributes to the emerging literature of sensory marketing by providing directions for future touch research by capturing the dynamic nature of haptics.
Understanding the circumstances and stakeholder perceptions of gun violence restraining order use in California: A qualitative study
Authors: Pallin Rocco , Tomsich Elizabeth , Schleimer Julia P. , Pear Veronica A. , Charbonneau Amanda , Wintemute Garen J. , Knoepke Christopher E. 
Published: November 2021

AbstractResearch SummaryRisk‐based firearm removal policies are relatively new, and research on their implementation and effectiveness is limited. Using an interpretive phenomenological approach, we interviewed stakeholders in California's gun violence restraining order (GVRO) process to learn about circumstances in which GVROs are appropriate. Two primary themes emerged: (1) GVROs are most useful when there is acute risk of harm with a firearm, in the context of cognitive decline, or as related cases proceed through the courts, and (2) GVROs fill a gap in the policy landscape. Perceptions varied regarding the role of GVROs among preexisting violence prevention tools. Several informants perceived racial/ethnic disparities in GVRO use.Policy ImplicationsUnderstanding practitioners’ perceptions of GVRO utility may help inform implementation and ensure that these policies equitably improve public health and safety. These results highlight the need for additional research on the impact of GVROs and possible disparities in use.
“Builders of a New Social Bond”: Fratelli Tutti on Good Politics and the Challenge of Inequality
Authors: Mulligan Suzanne 
Published: November 2021

AbstractThis article examines Pope Francis’s political vision as outlined in Fratelli Tutti, and argues that inequality presents a challenge to achieving what he calls “good politics.” Political trust is being eroded throughout the world due to corruption and rising economic disparities, with potentially damaging consequences for democratic politics. Inequality contributes to political instability since it weakens the common good, social solidarity, and critical citizenship. The social doctrine of the Catholic Church provides the context from which various forms of inequality will be examined, with particular focus on Fratelli Tutti.
The characteristics of residual pneumoperitoneum after laparoscopic colorectal surgery
Authors: Fukuhara Sotaro , Egi Hiroyuki , Kochi Masatoshi , Shimizu Wataru , Takakura Yuji , Taguchi Kazuhiro , Nakashima Ikki , Sumi Yusuke , Akabane Shintaro , Sato Koki , Yoshinaka Hisaaki , Teraoka Yoshifumi , Hattori Minoru , Ohdan Hideki 
Published: November 2021

AbstractIntroductionDespite the popularity of laparoscopic surgery, it remains unclear whether residual pneumoperitoneum influences the patient's postoperative course. This study aimed to evaluate the characteristics of residual pneumoperitoneum.MethodsThis retrospective study included 201 Japanese patients who had undergone elective laparoscopic colorectal surgery. The patients were divided into groups, with and without anastomotic failure; the non‐anastomotic failure group was further divided into subgroups, with and without residual pneumoperitoneum. Patient characteristics were compared between the various groups.ResultsThe group with residual pneumoperitoneum included 57 patients (30.3%). Percutaneous drainage was required for one patient with residual pneumoperitoneum. Univariate analyses revealed that residual pneumoperitoneum was associated with low values for body mass index (BMI) and subcutaneous fat area (SFA). Furthermore, relative to the group with anastomotic failure, the group without anastomotic failure but with residual pneumoperitoneum had lower values for inflammatory markers.ConclusionLow BMI and SFA values were identified as risk factors for residual pneumoperitoneum. Inflammatory markers may be useful as indicators for avoiding emergent surgery when it is difficult to differentiate between asymptomatic residual pneumoperitoneum and free air related to anastomotic failure.