bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overlapping Representation of Basic Tastes in the Human Gustatory Cortex
Authors: Zhang Du , Wang Xiaoxiao , Wang Yanming , Nguchu Benedictor Alexander , Jiang Zhoufang , Shi Chenwei , Qiu Bensheng 
Published: November 2021

AbstractThe topological representation is a fundamental property of human primary sensory cortices. The human gustatory cortex (GC) responds to the five basic tastes: bitter, salty, sweet, umami, and sour. However, the topological representation of the human gustatory cortex remains controversial. Through functional magnetic resonance imaging(fMRI) measurements of human responses to the five basic tastes, the current study aimed to delineate the taste representations within the GC. During the scanning, the volunteers tasted solutions of the five basic tastes, then washed their mouths with the tasteless solution. The solutions were then sucked from the volunteers’ mouths, eliminating the action of swallowing. The results showed that the bilateral mid-insula activated most during the taste task, and the active areas were mainly in the precentral and central insular sulcus. However, the regions responding to the five basic tastes are substantially overlapped, and the analysis of contrasts between each taste response and the averaged response to the remaining tastes does not report any significant results. Furthermore, in the gustatory insular cortex, the multivariate pattern analysis (MVPA) was unable to distinguish the activation patterns of the basic tastes, suggesting the possibility of weakly clustered distribution of the taste-preference neural activities in the human insular cortex. In conclusion, the presented results suggest overlapping representations of the basic tastes in the human gustatory insular cortex.
Evaluation of machine learning models for proteoform retention and migration time prediction in top-down mass spectrometry
Authors: Chen Wenrong , McCool Elijah N. , Sun Liangliang , Zang Yong , Ning Xia , Liu Xiaowen 
Published: November 2021

AbstractReversed-phase liquid chromatography (RPLC) and capillary zone electrophoresis (CZE) are two popular proteoform separation methods in mass spectrometry (MS)-based top-down proteomics. The prediction of proteoform retention time in RPLC and migration time in CZE provides additional information that can increase the accuracy of proteoform identification and quantification. Whereas existing methods for retention and migration time prediction are mainly focused on peptides in bottom-up MS, there is still a lack of methods for the problem in top-down MS. We systematically evaluated 6 models for proteoform retention and/or migration time prediction in top-down MS and showed that the Prosit model achieved a high accuracy (R2> 0.91) for proteoform retention time prediction and that the Prosit model and a fully connected neural network model obtained a high accuracy (R2> 0.94) for proteoform migration time prediction.
dynaPhenoM: Dynamic Phenotype Modeling from Longitudinal Patient Records Using Machine Learning
Authors: Zhang Hao , Zang Chengxi , Xu Jie , Zhang Hansi , Fouladvand Sajjad , Havaldar Shreyas , Su Chang , Cheng Feixiong , Glicksberg Benjamin S. , Chen Jin , Bian Jiang , Wang Fei 
Published: November 2021

AbstractIdentification of clinically meaningful subphenotypes of disease progression can facilitate better understanding of disease heterogeneity and underlying pathophysiology. We propose a machine learning algorithm, termed dynaPhenoM, to achieve this goal based on longitudinal patient records such as electronic health records (EHR) or insurance claims. Specifically, dynaPhenoM first learns a set of coherent clinical topics from the events across different patient visits within the records along with the topic transition probability matrix, and then employs the time-aware latent class analysis (T-LCA) procedure to characterize each subphenotype as the evolution of these learned topics over time. The patients in the same subphenotype have similar such topic evolution patterns. We demonstrate the effectiveness and robustness of dynaPhenoM on the case of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) progression on three patient cohorts, and five informative subphenotypes were identified which suggest the different clinical trajectories for disease progression from MCI to AD.
Removing unwanted variation from large-scale cancer RNA-sequencing data
Authors: Molania Ramyar , Foroutan Momeneh , Gagnon-Bartsch Johann A. , Gandolfo Luke , Olshansky Gavriel , Dobrovic Alexander , Papenfuss Anthony T , Speed Terence P 
Published: November 2021

AbstractThe accurate identification and effective removal of unwanted variation are essential to derive meaningful biological results from RNA-seq data, especially when the data come from large and complex studies. We have used The Cancer Genome Atlas (TCGA) RNA-seq data to show that library size, batch effects, and tumor purity are major sources of unwanted variation across all TCGA RNA-seq datasets and that existing gold standard approaches to normalizations fail to remove this unwanted variation. Additionally, we illustrate how different sources of unwanted variation can compromise downstream analyses, including gene co-expression, association between gene expression and survival outcomes, and cancer subtype identifications. Here, we propose the use of a novel strategy, pseudo-replicates of pseudo-samples (PRPS), to deploy the Removing Unwanted Variation III (RUV-III) method to remove different sources of unwanted variation from large and complex gene expression studies. Our approach requires at least one roughly known biologically homogenous subclass of samples shared across sources of unwanted variation. To create PRPS, we first need to identify the sources of unwanted variation, which we will call batches in the data. Then the gene expression measurements of biologically homogeneous sets of samples are averaged within batches, and the results called pseudo-samples. Pseudo-samples with the same biology and different batches are then defined to be pseudo-replicates and used in RUV-III as replicates. The variation between pseudo-samples of a set pseudo-replicates is mainly unwanted variation. We illustrate the value of our approach by comparing it to the TCGA normalizations on several TCGA RNA-seq datasets. RUV-III with PRPS can be used for any large genomics project involving multiple labs, technicians, or platforms.
Comparative genomics among three cyst nematode species reveals distinct evolutionary histories among effector families and an irregular distribution of effector-associated promoter motifs
Authors: van Steenbrugge Joris J.M. , van den Elsen Sven , Holterman Martijn , Lozano-Torres Jose L. , Putker Vera , Thorpe Peter , Goverse Aska , Sterken Mark G. , Smant Geert , Helder Johannes 
Published: November 2021

AbstractPotato cyst nematodes (PCNs), an umbrella term used for two species, Globodera pallida and G. rostochiensis, belong worldwide to the most harmful pathogens of potato. Pathotype-specific host plant resistances are an essential handle for PCN control. However, the poor delineation of G. pallida pathotypes hampers the efficient use of available host plant resistances. Long-read sequencing technology allowed us to generate a new reference genome of G. pallida population D383 and, as compared to the current reference, the new genome assembly is 42 times less fragmented. For comparison of diversification patterns of six effector families between G. pallida and G. rostochiensis, an additional reference genome was generated for an outgroup, the beet cyst nematode Heterodera schachtii (IRS population). Large evolutionary contrasts in effector family topologies were observed. While VAPs diversified before the split between the three cyst nematode species, the families GLAND5 and GLAND13 only expanded in PCN after their separation from the genus Heterodera. Although DNA motifs in the promoter regions thought to be involved in the orchestration of effector expression (‘DOG boxes’) were present in all three cyst nematode species, their presence is not a necessity for dorsal gland-produced effectors. Notably, DOG box dosage was only loosely correlated with expression level of individual effector variants. Comparison of the G. pallida genome with those of two other cyst nematodes underlined the fundamental differences in evolutionary history between effector families. Re-sequencing of PCN populations with deviant virulence characteristics will allow for the linking of these characteristics with the composition of the effector repertoire as well as for the mapping of PCN diversification patterns resulting from extreme anthropogenic range expansion.
Garlic-derived organosulfur compounds regulate metabolic and immune pathways in macrophages and attenuate intestinal inflammation in mice
Authors: Zhu Ling , Myhill Laura J. , Andersen-Civil Audrey I.S. , Thamsborg Stig M. , Blanchard Alexandra , Williams Andrew R. 
Published: November 2021

AbstractScopeGarlic is a source of bioactive phytonutrients that may have anti-inflammatory or immunomodulatory properties. The mechanism(s) underlying the bioactivity of these compounds and their ability to regulate responses to enteric infections remains unclear.Methods and ResultsWe investigated if a garlic-derived preparation (PTSO-PTS) containing two organosulfur metabolites, propyl-propane thiosulfonate (PTSO) and propyl-propane thiosulfinate (PTS), regulated inflammatory responses in murine macrophages and intestinal epithelial cells (IEC)in vitro,as well as in a model of enteric parasite-induced inflammation. PTSO-PTS decreased lipopolysaccharide-induced secretion of TNFα, IL-6 and IL-27 in macrophages. RNA-sequencing demonstrated that PTSO-PTS strongly suppressed pathways related to immune and inflammatory signaling. PTSO-PTS induced the expression of a number of genes involved in antioxidant responses in IEC during exposure to antigens from the parasiteTrichuris muris. In vivo,PTSO-PTS did not affectT. murisestablishment or intestinal T-cell responses but significantly altered caecal transcriptomic responses. Notably, a reduction inT. muris-induced expression ofTnf, Saa2andNos2was observed.ConclusionGarlic-derived organosulfur compounds exert anti-inflammatory effects in macrophages and IEC, and regulate gene expression during intestinal infection. These compounds and related organic molecules may thus hold potential as functional food components to improve gut health in humans and animals.
Annexin A4 senses membrane curvature in a density dependent manner
Authors: Florentsen Christoffer D. , Daniels Joshua A. , Moreno-Pescador Guillermo , Qoqaj Iliriana , Nylandsted Jesper , Bendix Poul Martin 
Published: November 2021

AbstractAnnexins (ANXs) are a family of peripheral membrane binding proteins which play a vital role in the maintenance and function of cellular membranes. These proteins are known to be part of the plasma membrane repair machinery where they are known to bind to negatively charged lipids in the cell membrane in a calcium dependent manner. The shape of the plasma membrane is known to be a regulator of protein density and thereby affects several biological functions of the cell such as exo-and endocytosis, cell motility, immune responses and also membrane repair. Membrane deformation and curvature sensing by proteins is a well described phenomenon which can assist in recruitment of specific proteins to certain regions in the cell and facilitate membrane bending. Following ruptures in the plasma membrane, calcium influx assist in the association of ANXs with the membrane around the ruptured area. Due to the expected increase in curvature at the damaged membrane site, it has been suggested that both membrane curvature and Ca2+ participate in the recruitment of ANXs. We have investigated the curvature sensing of ANXA4 in giant unilamellar vesicles (GUVs) by pulling high curvature membrane tethers from the vesicle surface using optical tweezers showing that ANXA4 recruitment increases with higher membrane curvature. We also describe an assay for determining protein density on the plasma membrane by utilizing ANXA4’s property as a calcium dependent membrane binding protein. This new assay allows us to investigate the effect of protein density on curvature sensing.
ParS-independent recruitment of the bacterial chromosome-partitioning protein ParB
Authors: Tišma Miloš , Panoukidou Maria , Antar Hammam , Soh Young-Min , Barth Roman , Pradhan Biswajit , van der Torre Jaco , Michieletto Davide , Gruber Stephan , Dekker Cees 
Published: November 2021

AbstractThe ParABS system plays an essential role in prokaryotic chromosome segregation. After loading at the parS site on the genome, ParB proteins rapidly redistribute to distances of ~15 kb away from the loading site. It has remained puzzling how this large-distance spreading can occur along DNA that is loaded with hundreds of proteins. Using single-molecule in vitro visualization, we here show that, unexpectedly, ParB can load onto DNA independently and distantly of parS, whereby loaded ParB molecules are themselves able to recruit additional ParB proteins from bulk. Strikingly, this recruitment can occur in-cis but also in-trans whereby, at low tensions within the DNA, newly recruited ParB can bypass roadblocks as it gets loaded to spatially proximal but genomically distant DNA regions. The data are supported by Molecular Dynamics simulations which also show that cooperative ParB-ParB recruitment enhances spreading. ParS-independent recruitment explains how ParB can cover substantial genomic distance during chromosome segregation which is vital for the bacterial cell cycle.
Inhibitory Cerebellar Stimulation Increases Cortical Activation: Evidence for Cerebellar Scaffolding of Cortical Processing
Authors: Maldonado Ted , Jackson T. Bryan , Bernard Jessica A. 
Published: November 2021

AbstractWhile the cerebellum makes known contributions to non-motor task performance, the role of the structure remains unknown. One possibility is that the cerebellum allows for the offloading of cortical processing, providing support during task performance, using internal models. The current work used transcranial direct current stimulation to modulate cerebellar function and investigate the impact on cortical activation patterns. Participants received stimulation over the right cerebellum before a functional magnetic resonance imaging scan where participants completed a sequence learning and a working memory task. We predicted that cathodal stimulation would improve, and anodal stimulation would hinder task performance and cortical activation. We found that anodal cerebellar stimulation resulted in increased bilateral cortical activation, particularly in parietal and frontal regions known to be involved in cognitive processing. This suggests that if the cerebellum is not functioning optimally, there is a greater need for cortical resources.
Microglia ferroptosis is prevalent in neurodegenerative disease and regulated by SEC24B
Authors: Ryan Sean K. , Zelic Matija , Han Yingnan , Teeple Erin , Chen Luoman , Sadeghi Mahdiar , Shankara Srinivas , Guo Lilu , Li Cong , Pontarelli Fabrizio , Jensen Elizabeth H. , Kumar Dinesh , Zhang Mindy , Gans Joseph , Zhang Bailin , Proto Jonathan , Saleh Jacqueline , Dodge James C. , Rajpal Deepak , Ofengeim Dimitry , Hammond Timothy R. 
Published: November 2021

AbstractIron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). One prominent feature of affected brain regions are iron-loaded microglia, but how iron overload influences microglia physiology and disease response is poorly understood. Here we show that microglia are highly susceptible to ferroptosis, an iron-dependent form of cell death. In a tri-culture of human iPSC-derived neurons, astrocytes, and microglia, under ferroptosis-inducing conditions, microglia undergo a drastic shift in cell state, with increased ferritin levels, disrupted glutathione homeostasis, and altered cytokine signaling. Similar ferroptosis-associated signature (FAS) microglia were uncovered in PD, and the signature was also found in a large cohort of PD patient blood samples, raising the possibility that ferroptosis can be identified clinically. We performed a genome-wide CRISPR screen which revealed a novel regulator of ferroptosis, the vesicle trafficking gene SEC24B. A small molecule screen also nominated several candidates which blocked ferroptosis, some of which are already in clinical use. These data suggest that ferroptosis sits at the interface of cell death and inflammation, and inhibition of this process in microglia and other brain cells may provide new ways for treating neurodegenerative disease.
Unpacking strategic corporate social responsibility in the time of crisis: a critical review
Authors: Ashraf Zubaida , Afshan Gul , Sahibzada Umar Farooq 
Published: November 2021

PurposeAn increasing number of organizations focus on creating value in economics and growing their aspect, encompassing human, social and environmental perspectives. Traditionally, organizations mostly contained corporate social responsibility (CSR) as their actions only in an economically favorable situation. However, CSR can also be used in an unfavorable time as a strategic process to recover and sustain the organization during a crisis. The purpose of this study is to review six years (2015-2021) articles published on strategic CSR.Design/methodology/approachThe literature review of the current study examines through source data and combination findings the role of strategic CSR during a time of crisis. The search was conducted using Google Scholars, Psych Info, Emerald Insight, Science Direct and ProQuest. The study reviewed six years of articles on strategic CSR (2015–2021).FindingsThe paper concludes by suggesting propositions and a model that indicated that effective communication encourages employees and external stakeholders to participate and enhance their contribution during the crisis and help gain a competitive advantage.Research limitations/implicationsThe present review demonstrated managing crisis by incorporating strategic CSR initiatives. The role of communication is important for understanding the crisis, which builds a trust-based relationship with employees and external stakeholders and enhances their participation and engagement that can help sustain during the crisis. This study will help the organizations during the time of crisis because strategic CSR initiatives reduce the negative effect of the crisis and help achieve organizational competitive advantages.Originality/valueThe present review bridges the gap in strategic CSR during the COVID-19 crisis interface. This review aims to understand the role of strategic CSR during the time COVID-19 of crisis. This study contributes to the strategic CSR research by giving clarity regarding the managing crises of organizations.
Exploring a natural baseline for large‐herbivore biomass in ecological restoration
Authors: Fløjgaard Camilla , Pedersen Pil Birkefeldt Møller , Sandom Christopher J. , Svenning Jens‐Christian , Ejrnæs Rasmus 
Published: November 2021

Abstract

Large herbivores provide key ecosystem processes, but have experienced massive historical losses and are under intense pressure, leaving current ecosystems with dramatically simplified faunas relative to the long‐term evolutionary norm. Hampered by a shifting baseline, natural levels of large‐herbivore biomass are poorly understood and seldom targeted. This ‘Decade of ecosystem restoration’ calls for evidence‐based targets for restoring the natural diversity and biomass of large herbivores.

We apply the scaling of the consumer–producer relationship to a global dataset of large‐herbivore density in natural areas. The analyses reveal that African ecosystems generally have much higher large‐herbivore biomass and also the strongest consumer–producer relationship. For Europe, Asia and South America, there are no significant relationships with primary productivity indicative of impoverished faunas. Compared to expectations from the African scaling relation, large‐herbivore biomass in ecosystems outside Africa is considerably lower than expected.

Synthesis and applications. Ecological restoration and rewilding entail restoration of a natural grazing process. Our findings indicate that many nature reserves are depleted in large‐herbivore biomass, judged from their primary productivity. Meanwhile, overexploitation by seasonal livestock grazing takes place in other areas. It is thus difficult, but urgent, to reach scientific consensus regarding a natural baseline for large‐herbivore biomass. Until such agreement has been reached, we recommend to manage, or rewild, large herbivores in year‐round near‐natural grazing and without predefined density targets, but following natural and fluctuating resource availability with minimal management intervention. The establishment of experimental rewilding sites with reactive herbivore management is needed to further advance our understanding of natural grazing density.
Human Trafficking, SM v Croatia and the Conceptual Evolution of Article 4 ECHR
Authors: Hughes Kirsty 
Published: November 2021

AbstractOver the last decade the European Court of Human Rights has sought to reinterpret Article 4 ECHR in ways that render it applicable to human trafficking and modern slavery. Yet whilst this accorded Article 4 ECHR a vital role, ambiguity pervaded the question of what constitutes ‘human trafficking’; an issue that came to the fore in SM v Croatia, ultimately culminating in the first Grand Chamber human trafficking judgment. This analysis piece responds to these developments by drawing out and reflecting upon the conceptual framework for human trafficking and Article 4 ECHR, identifying what we now know, and equally what remains unknown, about this important right. In this regard it highlights significant differences of opinion within the Court. Underpinning those differences are diverging views as to both the scope of Article 4 ECHR, and the role of the Court, such that radically different future directions remain both possible and contested.