bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translation rescue by targeting Ppp1r15a upstream open reading frame in vivo
Authors: Kidwell Ashley , Yadav Shiv Pratap Singh , Maier Bernhard , Zollman Amy , Ni Kevin , Halim Arvin , Janosevic Danielle , Myslinski Jered , Syed Farooq , Zeng Lifan , Waffo Alain Bopda , Banno Kimihiko , Xuei Xiaoling , Doud Emma H. , Dagher Pierre C. , Hato Takashi 
Published: December 2021

AbstractThe eIF2 initiation complex is central to maintaining a functional translation machinery. Extreme stress such as life-threatening sepsis exposes vulnerabilities in this tightly regulated system, resulting in an imbalance between the opposing actions of kinases and phosphatases on the main regulatory subunit eIF2α. Here, we report that translation shutdown is a hallmark of established sepsis-induced kidney injury brought about by excessive eIF2α phosphorylation and sustained by blunted expression of the counterregulatory phosphatase subunit Ppp1r15a. We determined that the blunted Ppp1r15a expression persists because of the presence of an upstream open reading frame (uORF). Overcoming this barrier with genetic approaches enabled the derepression of Ppp1r15a, salvaged translation and improved kidney function in an endotoxemia model. We also found that the loss of this uORF has broad effects on the composition and phosphorylation status of the immunopeptidome that extended beyond the eIF2α axis. Collectively, our findings define the breath and potency of the highly conserved Ppp1r15a uORF and provide a paradigm for the design of uORF-based translation rheostat strategies. The ability to accurately control the dynamics of translation during sepsis will open new paths for the development of therapies at codon level precision.
Tabula Microcebus: A transcriptomic cell atlas of mouse lemur, an emerging primate model organism
Authors:   The Tabula Microcebus Consortium, Ezran Camille , Liu Shixuan , Chang Stephen , Ming Jingsi , Botvinnik Olga , Penland Lolita , Tarashansky Alexander , de Morree Antoine , Travaglini Kyle J. , Zhao Jia , Wang Gefei , Hasegawa Kazuteru , Sin Hosu , Sit Rene , Okamoto Jennifer , Sinha Rahul , Zhang Yue , Karanewsky Caitlin J. , Pendleton Jozeph L. , Morri Maurizio , Perret Martine , Aujard Fabienne , Stryer Lubert , Artandi Steven , Fuller Margaret , Weissman Irving L. , Rando Thomas A. , Ferrell James E. , Wang Bo , De Vlaminck Iwijn , Yang Can , Casey Kerriann M. , Albertelli Megan A. , Pisco Angela Oliveira , Karkanias Jim , Neff Norma , Wu Angela Ruohao , Quake Stephen R. , Krasnow Mark A. 
Published: December 2021

ABSTRACTMouse lemurs are the smallest, fastest reproducing, and among the most abundant primates, and an emerging model organism for primate biology, behavior, health and conservation. Although much has been learned about their physiology and their Madagascar ecology and phylogeny, little is known about their cellular and molecular biology. Here we used droplet- and plate-based single cell RNA-sequencing to profile 226,000 cells from 27 mouse lemur organs and tissues opportunistically procured from four donors clinically and histologically characterized. Using computational cell clustering, integration, and expert cell annotation, we defined and biologically organized over 750 mouse lemur molecular cell types and their full gene expression profiles. These include cognates of most classical human cell types, including stem and progenitor cells, and the developmental programs for spermatogenesis, hematopoiesis, and other adult tissues. We also described dozens of previously unidentified or sparsely characterized cell types and subtypes. We globally compared cell type expression profiles to define the molecular relationships of cell types across the body, and explored primate cell and gene expression evolution by comparing mouse lemur cell transcriptomes to those of human, mouse, and macaque. This revealed cell type specific patterns of primate specialization, as well as many cell types and genes for which lemur provides a better human model than mouse. The atlas provides a cellular and molecular foundation for studying this primate model organism, and establishes a general approach for other emerging model organisms.
FLAMs: A self-replicating ex vivo model of alveolar macrophages for functional genetic studies
Authors: Thomas Sean , Wierenga Kathryn , Pestka James , Olive Andrew J 
Published: December 2021

ABSTRACTAlveolar macrophages (AMs) are tissue resident cells in the lungs derived from the fetal liver that maintain lung homeostasis and respond to inhaled stimuli. While the importance of AMs is undisputed, they remain refractory to standard experimental approaches and high-throughput functional genetics as they are challenging to isolate and rapidly lose AM properties in standard culture. This limitation hinders our understanding of key regulatory mechanisms that control AM maintenance and function. Here, we describe the development of a new model, fetal liver-derived alveolar-like macrophages (FLAMs), which maintains cellular morphologies, expression profiles, and functional mechanisms similar to murine AMs. FLAMs combine treatment with two key cytokines for AM maintenance, GM-CSF and TGFβ. We leveraged the long-term stability of FLAMs to develop functional genetic tools using CRISPR-Cas9-mediated gene editing. Targeted editing confirmed the role of AM-specific gene Marco and the IL-1 receptor Il1r1 in modulating the AM response to crystalline silica. Furthermore, a genome-wide knockout library using FLAMs identified novel genes required for surface expression of the AM marker Siglec-F, most notably those related to the peroxisome. Taken together, our results suggest that FLAMs are a stable, self-replicating model of AM function that enables previously impossible global genetic approaches to define the underlying mechanisms of AM maintenance and function.
Phylogenomics unravels the early diversification of fungi
Authors: Strassert Jürgen F. H. , Monaghan Michael T. 
Published: December 2021

SummaryPhylogenomic analyses have boosted our understanding of the evolutionary trajectories of all living forms by providing continuous improvements to the tree of life1–5. Within this tree, fungi represent an ancient eukaryote group6, having diverged from the animals ∼1.35 billion years ago7. Estimates of the number of extant species range between 1.5 and 3.8 million8,9. Recent reclassifications and the discovery of the deep-branching Sanchytriomycota lineage10 have brought the number of proposed phyla to 2011; 21 if the Microsporidia are included12–14. Uncovering how the diverse and globally distributed fungi are related to each other is fundamental for understanding how their lifestyles, morphologies, and metabolic capacities evolved. To date, many of the proposed relationships among the phyla remain controversial and no phylogenomic study has examined the entire fungal tree using a taxonomically comprehensive data set and suitable models of evolution. We assembled and curated a 299-protein data set with a taxon sampling broad enough to encompass all recognised fungal diversity with available data, but selective enough to run computationally intensive analyses using best-fitting models. Using a range of reconstruction methods, we were able to resolve many contested nodes, such as a sister-relationship of Chytridiomyceta to all other non-Opisthosporidia fungi (with Chytridiomycota being sister to Monoblepharomycota + Neocallimastigomycota), a branching of Blastocladiomycota + Sanchytriomycota after the Chytridiomyceta but before other non-Opisthosporidia fungi, and a branching of Glomeromycota as sister to the Dikarya. Our most up-to-date fungal tree of life will serve as a springboard for future investigations on the evolution of fungi.
Contrastive Cycle Adversarial Autoencoders for Single-cell Multi-omics Alignment and Integration
Authors: Wang Xuesong , Hu Zhihang , Yu Tingyang , Wang Yixuan , Wang Ruijie , Wei Yumeng , Shu Juan , Ma Jianzhu , Li Yu 
Published: December 2021

ABSTRACTWe have entered the multi-omics era, and we can measure cells from different aspects. When dealing with such multi-omics data, the first step is to determine the correspondence among different omics. In other words, we should match data from different spaces corresponding to the same object. This problem is particularly challenging in the single-cell multi-omics scenario because such data are very sparse with extremely high dimensions. Secondly, matched single-cell multi-omics data are rare and hard to collect. Furthermore, due to the limitations of the experimental environment, the data are usually highly noisy. To promote the single-cell multi-omics research, we overcome the above challenges, proposing a novel framework to align and integrate single-cell RNA-seq data and single-cell ATAC-seq data. Our approach can efficiently map the above data with high sparsity and noise from different spaces to a low-dimensional manifold in a unified space, making the downstream alignment and integration straightforward. Compared with the other state-of-the-art methods, our method performs better on both simulated and real single-cell data. On the real data, the performance improvement on accuracy over the previous methods is up to 55.7% regarding scRNA-seq and scATAC-seq data integration. Downstream trajectory inference analysis shows that our tool can transfer the labels from scRNA-seq to scATAC-seq with very high accuracy, which indicates our method’s effectiveness.
Food Restriction Augmented Alpha1–Adrenergic Mediated Contraction in Mesenteric Arteries
Authors: Vorn Rany , Yoo Hae Young 
Published: December 2021

AbstractFood restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and α1- adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of α1–adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.
Metabolic potentials of Liquorilactobacillus nagelii AGA58 isolated from Shalgam based on genomic and functional analysis
Authors: Yetiman Ahmet , Ortakci Fatih 
Published: December 2021

AbstractThe aim of present study was to perform functional and genomic characterization of a novel Liquorilactobacillus nagelii AGA58 isolated from Shalgam to understand its metabolic potentials. AGA58 is gram-positive, catalase-negative and appears as short-rods under light-microscope. The AGA58 chromosome composed of a single linear chromosome of 2,294,535 bp that is predicted to carry 2151 coding sequences, including 45 tRNA genes, 4 rRNA operons. Genome has a GC content of 36.9% includes 45 pseudogenes, 32 transposases and one intact-prophage. AGA58 is micro-anaerobic owing to shorter doubling time and faster growth rate achieved compared microaerofilic condition. It carries flagellar biosynthesis protein-encoding genes predicting motile behavior. AGA58 is an obligatory homofermentative where hexose sugars such as galactose, glucose, fructose, sucrose, mannose, N-acetyl glucosamine, maltose, trehalose are fermented to lactate thru glycolysis and no acid production from pentose sugars achieved due to lack of key enzyme namely phosphoketolase in pentose phosphate pathway. Carbohydrate fermentation tests showed AGA58 cannot ferment pentoses which was also confirmed in silico. Putative pyruvate metabolism revealed formate, malate, oxaloacetate, acetate, acetaldehyde, acetoin and lactate forms from pyruvate. AGA58 predicted to carry bacteriocin genes for type A2 lantipeptide, Blp family class II bacteriocins showing antimicrobial potential of this bacterium which can be linked to antagonism tests that AGA58 can inhibit E. coli O157:H7, S. Typhimurium ATCC14028, and K. pneumonia ATCC13883. Moreoever, AGA58 is tolerant to acid and bile concentrations simulating the human gastrointestinal conditions. L. nagelii AGA58 depicting the probiotic potential of AGA58 as a first report in literature within same species.
Family level drivers of access to healthcare among persons with disabilities in the Bosomtwe district of Ghana
Authors: Acheampong Enoch , Nadutey Alberta , Bredu-Darkwa Peter , Agyei-Baffuor Peter , Kwaku Edusei Anthony 
Published: December 2021

Purpose
The perceptions of disability conditions held by parents and immediate family members directly determine the types of treatments that are likely to opt for persons with disabilities whenever they are ill. Family level drivers of access to healthcare among persons with disabilities in the Bosomtwe district of Ghana.

Design/methodology/approach
A qualitative case study was conducted in which data were collected from 60 participants selected purposively. Face-to-face interviews were conducted, and the results were presented thematically.

Findings
The drivers identified have been categorized into positive and negative depending on how they influenced persons with disabilities’ access to health care. Payment of medical bills, physical access support, the narration of health condition to a health-care provider, spiritual support, care and love were the positives while perceived spiritual cause of disability, preference for alternative treatment centers, unwillingness to support reproductive and specialized health care.

Research limitations/implications
This study had some limitations, and one of such is the non-inclusion of disabled people who had not been registered by the department of social welfare but resided in the district who could have provided rich information to the study. However, their exclusion did not affect the quality of data obtained, as those who were registered and selected for the study gave adequate information about the issues that were considered during the study.

Originality/value
Family members of persons with disabilities play key roles in promoting their access to health care; therefore, there is the need for stakeholders to put in measures that will limit misconceptions about disability not only for the general public but also for individuals like parents and immediate family members of persons with disabilities.
Ultrasound liver tumor segmentation using adaptively regularized kernel-based fuzzy C means with enhanced level set algorithm
Authors: Uplaonkar Deepak S. , Virupakshappa  , Patil Nagabhushan 
Published: December 2021

PurposeThe purpose of this study is to develop a hybrid algorithm for segmenting tumor from ultrasound images of the liver.Design/methodology/approachAfter collecting the ultrasound images, contrast-limited adaptive histogram equalization approach (CLAHE) is applied as preprocessing, in order to enhance the visual quality of the images that helps in better segmentation. Then, adaptively regularized kernel-based fuzzy C means (ARKFCM) is used to segment tumor from the enhanced image along with local ternary pattern combined with selective level set approaches.FindingsThe proposed segmentation algorithm precisely segments the tumor portions from the enhanced images with lower computation cost. The proposed segmentation algorithm is compared with the existing algorithms and ground truth values in terms of Jaccard coefficient, dice coefficient, precision, Matthews correlation coefficient,f-score and accuracy. The experimental analysis shows that the proposed algorithm achieved 99.18% of accuracy and 92.17% off-score value, which is better than the existing algorithms.Practical implicationsFrom the experimental analysis, the proposed ARKFCM with enhanced level set algorithm obtained better performance in ultrasound liver tumor segmentation related to graph-based algorithm. However, the proposed algorithm showed 3.11% improvement in dice coefficient compared to graph-based algorithm.Originality/valueThe image preprocessing is carried out using CLAHE algorithm. The preprocessed image is segmented by employing selective level set model and Local Ternary Pattern in ARKFCM algorithm. In this research, the proposed algorithm has advantages such as independence of clustering parameters, robustness in preserving the image details and optimal in finding the threshold value that effectively reduces the computational cost.
How human capital affects labor income share at the sectoral level?: Evidence from the EU-13 countries and the UK
Authors: Çelik Orkun 
Published: December 2021

PurposeThe author investigates the effects of human capital on labor income share in the 15 sectors of the European Union (EU)-13 countries and the United Kingdom (UK) over the period 2008–2015.Design/methodology/approachThe author employs pooled ordinary least squares (OLS) estimation with panel data, using the EU KLEMS database.FindingsThe results show that when education level increases, labor income share increases and gender-based labor income share differentials decrease. Return to education is higher in qualitative sectors in contrast with the other sectors. Moreover, there are gender-based labor income share differentials at the sectoral level. These differentials are higher in nonqualitative sectors, while they are relatively lower in qualitative sectors.Research limitations/implicationsThe biggest limitation of the study is that the data range cannot be expanded because of the database. The author is of opinion that the empirical findings will guide to policy makers in terms of wage setting.Originality/valueThe expected contribution of this study to the literature is to investigate the effect of human capital on labor income share at the sectoral level for the EU-13 countries and the UK. As far as the author knows, there is no study which investigates this topic at the sectoral level such a comprehensive, in the literature.
An investigation of influencer body enhancement and brand endorsement
Authors: Lefebvre Sarah , Cowart Kelly 
Published: December 2021

Purpose
As the cosmetic surgery industry grows and diversifies, societal beauty standards have shifted to include images of surgically enhanced bodies. With the increased use of influencer marketing, it is important for marketers to understand consumer perceptions of these modified appearances. This paper aims to use the lens of perceived morality (PM) to investigate consumer perceptions of cosmetic surgery services and the effect of enhanced body appearance on consumer interest in an endorsed brand. Interpersonal similarity (IS) is tested as a boundary condition.

Design/methodology/approach
A mixed-methods approach was taken with a qualitative study and two online experiments. Participants were recruited through snowball sampling (NStudy 1 = 133) and Amazon Mechanical Turk (NStudy 2 = 202; NStudy 3 = 270).

Findings
The themes uncovered in the qualitative study revealed that cosmetic surgery services were acceptable when internally motivated but may signal inauthenticity. The findings of Study 2 suggested consumer interest in an endorsed brand was negatively impacted by body enhancement (BE), with PM as the underlying mechanism. Study 3 results demonstrated IS moderated this effect. The indirect effect was significant only for those low in IS.

Originality/value
This research contributes to the underexplored area of cosmetic surgery services and its role in influencer marketing. The findings extend the literature on consumer attitudes and perceptions toward these services and provides insight into the intersection of BE and morality. The contribution is notable, as marketers increasing rely on social media influencers, many of whom have undergone cosmetic surgery services and enhanced their body appearance, to promote their brands.
Regenerative tourism in Aotearoa New Zealand – A new paradigm for the VUCA world
Authors: Major Josie , Clarke Debbie 
Published: December 2021

PurposeThe paper provides a summary of the findings from GOOD Awaits – The Regenerative Tourism New Zealand (NZ) Podcast and envisions a regenerative future for tourism in Aotearoa.Design/methodology/approachThis paper is based on the findings from the GOOD Awaits Podcast, a series of interviews with pioneers and practitioners of regenerative tourism. The podcast was created as a platform for the collective discovery of a new way forward for tourism in the wake of COVID-19, and the series provides a detailed summary of the regenerative tourism movement in NZ.FindingsThrough these interviews, a vision for a regenerative visitor economy in Aotearoa emerged. This new model is rooted in indigenous knowledge and living systems theory. It is a paradigm shift that allows us to see tourism as a living ecosystem and requires innovative economic models, such as social entrepreneurship, systems level changes to the way tourism operates and is governed, local tourism solutions with community thriving as the primary aim and much more collaboration both within tourism and across sectors.Originality/valueRegenerative tourism is an emerging model and one that is rapidly gaining traction in NZ and globally. The GOOD Awaits podcast is a unique, thoughtful and practical demonstration of what this model could look like in Aotearoa. It demonstrates the potential and feasibility of regenerative tourism practice, and the response has shown the desire for these conversations at a national and international scale. This paper is an accessible summary of the podcast's first season and has value for anyone interested in the regenerative tourism movement in Aotearoa.