bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Moral Status of Organ Donation and Transplantation Within Islamic Law: The Fiqh Council of North America’s Position
Authors: Padela Aasim I. , Auda Jasser 
Published: February 2020

Background.
Muslim communities tend to hold more negative attitudes toward organ donation than other communities. These views, in part, reflect the diverse views of Islamic scholars who debate the conditions under which donation and transplantation is morally licit. In December 2018, the Fiqh Council of North America (FCNA) weighed in on the US context of donation and transplantation through an Islamic ethico-legal verdict (fatwa).

Methods.
Between 2016 and 2018, FCNA members engaged in multidisciplinary research using conventions of collective Islamic moral deliberation. They examined rulings on organ donation and transplantation issued by Islamic jurists and juridical councils abroad, convened with organ donation and transplantation professionals and stakeholders including families and patients, and consulted medical and bioethics experts.

Results.
FCNA judges organ donation to be morally permissible from the perspective of Islamic law and ethics, subject to several conditions. These include first-person authorization, that donation occur either while living or after circulatory declaration of death, harm to the donor is minimized, reproductive organs are not donated, among others. Organ transplantation, in general, was also deemed licit.

Conclusions.
FCNA’s verdict uniquely addresses American contexts and has several clinical practice implications. By sharing their perspective with academic and professional stakeholders, the council aims to provide nuanced guidance for assisting Muslims in making informed choices regarding these procedures and further societal dialogue on the ethics and practices of donation and transplantation.
Impact of rare and common genetic variation in the Interleukin-1 pathway on human cytokine responses
Authors: van Deuren Rosanne C. , Arts Peer , Cavalli Giulio , Jaeger Martin , Steehouwer Marloes , van de Vorst Maartje , Gilissen Christian , Joosten Leo A.B. , Dinarello Charles A. , Mhlanga Musa M. , Kumar Vinod , Netea Mihai G. , van de Veerdonk Frank L. , Hoischen Alexander 
Published: February 2020

ABSTRACTBackgroundInterleukin(IL)-1 signaling is of major importance in human innate cytokine responses. Common variants in related genes have been linked to various inflammation-mediated diseases and stimulation-induced cytokine responses, but the role of rare variants remains to be elucidated.MethodsIn this study, we characterize the role of rare and common genetic variation, as identified by molecular inversion probe-based sequencing, in 48 genes related to the IL-1 pathway. Using a systems biology approach, we examined the inter-individual variability ofin vitrostimulation-specific human cytokine responses from 463 healthy individuals of the Human Functional Genomics Project and assessed the role of rare and common genetic variants, separately and combined, by means of the Sequence Kernel Association Test.ResultsWe identified strong associations for rare genetic variants inNCF4(adjP=7.2E−05) andCASP1(adjP=3.0E−05) with IL-6 production in response to PHA and LPS stimulation, respectively. In addition, common variants inIL36AandIL38were associated to bothC. albicans-induced IL-1β (IL36AadjP=0.0442;IL38adjP=0.0092) and IL-6 production (IL36AadjP=0.0037;IL38adjP=0.0082), an effect that was stronger at the subpathway level both for IL-1β (adjP=0.0017) and IL-6 (adjP=1.8E−04). The common variant signature for the IL-1β and IL-6 response toC. albicanswas confirmed by an association with all anti-inflammatory genes (adjP=1.87E−03andadjP=5.75E−04), and we validated this finding for non-coding common variants. Lastly, we identified a burden of rare variants in pro-inflammatory genes and LPS-induced IL-6 production (adjP=2.42E−04), and a new role for anti-inflammatory rare variants onS. aureus-stimulated IL-6 production (adjP=6.71E−03).ConclusionsIn conclusion, we show that both common and rare genetic variation in genes of the IL-1 pathway, separately and combined, differentially influencein vitrocytokine responses to various stimuli in healthy individuals. This study therefore accentuates potential mechanisms that are translatable into new hypothesis-driven characterization of common and rare variant involvement in a wide variety of inflammatory and immunological mechanisms and diseases.
Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
Authors: Qi Furong , Qian Shen , Zhang Shuye , Zhang Zheng 
Published: February 2020

AbstractThe new coronavirus (2019-nCoV) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by 2019-nCov to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. 2019-nCoV may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted “CellPhoneDB” analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.
Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)
Authors: He Jiahua , Tao Huanyu , Yan Yumeng , Huang Sheng-You , Xiao Yi 
Published: February 2020

AbstractSince December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.
Ecological niche models as hypothesis generators of functional genetic differentiation and potential local adaptation in a Mediterranean alpine ecosystem
Authors: Morente-López Javier , Kass Jamie M. , Lara-Romero Carlos , Serra-Diaz Josep María , Soto-Correa José Carmen , Anderson Robert P. , Iriondo José María 
Published: February 2020

AbstractGeographically disparate populations within a species’ range may show important differences including variation in ecological, demographic, genetic and phenotypic characteristics. Based on the Center-Periphery Hypothesis, it is often assumed that environmental conditions are optimal in the geographic center of the range and stressful or suboptimal at the periphery, implying ecological marginality is concordant with geographic periphery. But this assumption has been challenged as geographical and ecological gradients are not necessarily concordant. The conservation value of populations inhabiting environmentally marginal areas is still under debate and is closely related with their evolutionary potential. Strong selective pressures caused by stressful conditions may generate novel adaptations in marginal areas, conferring these populations distinct evolutionary potential. But populations inhabiting marginal areas may also show reductions in neutral and adaptive genetic diversity via drift and inbreeding.In this work we explore the potential of ecological niche models (ENMs) to identify environmentally optimal and marginal areas, as well as the principal putative selective pressures likely to act. To do so, we built a carefully parameterized ENM ofSilene ciliata, a dominant plant species of Mediterranean alpine habitats. Complementarily, we selected wild populations inhabiting contrasting environmental conditions and carried out common garden experiments to detect genetic differentiation among populations associated with functional traits. With the resulting information, we tested whether environmentally marginal populations defined by the ENM had genetically differentiated phenotypes that are potentially adaptive and, thus, of conservation value.We found genetically based phenotypic differentiation of phenological traits between populations inhabiting areas identified by the ENM as marginal and optimal, as well as between populations with different habitat suitability values. Results supported ENMs as powerful tools for determining environmental marginality and identifying selection pressures, and thus also as hypothesis generators for divergent selection. Furthermore, genetically based phenotypic differentiation found underlines the potential adaptive value of populations inhabiting marginal areas. The approach developed here provides a theoretically justified and practical way to study adaptive processes and provide insights about the conservation value of marginal populations.
A causal role for estradiol in human reinforcement learning
Authors: Veselic Sebastijan , Jocham Gerhard , Gausterer Christian , Wagner Bernhard , Ernhoefer-Reßler Miriam , Lanzenberger Rupert , Lamm Claus , Eisenegger Christoph , Vermeer Annabel Losecaat 
Published: February 2020

AbstractThe sex hormone estrogen is hypothesized to play a key role in human cognition via its interactions with the dopaminergic system. Work in rodents has shown that estrogen’s most potent form, estradiol, impacts striatal dopamine functioning predominately via increased D1-receptor signalling, while human work has suggested that high estradiol levels are associated with altered reward sensitivity. Here, we addressed two fundamental questions: 1) whether estradiol causally alters reward sensitivity in men, and 2) whether this effect of estradiol is moderated by individual variation in polymorphisms of dopaminergic genes. To test this, we performed a double-blind placebo-controlled administration study in which hundred men received either a single dose of estradiol (2 mg) or placebo. We found that estradiol administration increased reward sensitivity, which was moderated by baseline dopamine. This was observed in choice behaviour and increased learning rates. These results confirm a causal role of estradiol in reinforcement learning in men that is moderated by the striatal dopaminergic pathway.
Pangolin homology associated with 2019-nCoV
Authors: Zhang Tao , Wu Qunfu , Zhang Zhigang 
Published: February 2020

AbstractTo explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.
Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knockout, and LacZ knockin mice
Authors: Kwak Hoyun , Cho Eun-Ho , Cho Eun Bee , Lee Yoo-Na , Shahapal Anu , Yong Hyo Jeong , Reyes-Alcaraz Arfaxad , Jeong Yongwoo , Lee Yerim , Lee Minhyeok , Ha Nui , Oh Sitaek , Lee Jae Keun , Lee Won Suk , Kim Won Kyum , Hwang Jong-Ik , Seong Jae Young 
Published: February 2020

ABSTRACTFAM19A5 is a novel secretory protein primarily expressed in the brain. However, a recent study reported that FAM19A5 is an adipocyte-derived adipokine that regulates vascular smooth muscle function through sphingosine-1-phosphate receptor 2 (S1PR2). In our study, we investigated FAM19A5 transcript and protein levels in peripheral tissues, including adipose tissues, from wild-type, FAM19A5 knockout, and FAM19A5 LacZ knockin mice. We found that FAM19A5 transcript levels in the central nervous system were much greater than those in any of the peripheral tissues, including adipose tissues. Furthermore, the FAM19A5 protein levels in adipose and reproductive tissues were below detectable limits for Western blot analysis. Additionally, we found that the FAM19A5 protein did not interact with S1PR2 in terms of G protein-mediated signal transduction, β-arrestin recruitment, or ligand-mediated internalization. Taken together, our findings revealed basal levels of FAM19A5 transcripts and proteins in peripheral tissues, confirming its primary expression in the central nervous system and lack of significant interaction with S1PR2.
Molecular classification of the placebo effect in nausea
Authors: Meissner Karin , Lutter Dominik , Toerne Christine von , Haile Anja , Woods Stephen C. , Hoffmann Verena , Ohmayer Uli , Hauck Stefanie M. , Tschöp Matthias 
Published: February 2020

ABSTRACTNumerous studies have shown that the mere expectation improvement can alleviate symptoms in various conditions. These ‘placebo effects’ often include reliable changes in central and peripheral organ systems. Here, we tested for the first time whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 healthy participants were exposed to a 20-min vection stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and gastric activity could be verified. Using state-of-the-art proteomics, 74 differentially regulated proteins were identified in placebo-treated participants as compared to no-treatment controls. Gene ontology (GO) enrichment analyses of these proteins revealed acute-phase proteins as well as microinflammatory proteins to be reliable plasma correlates of the placebo effect. Regression analyses showed that day-adjusted scores of nausea indices in the placebo group were predictable by the identified GO protein signatures. We next identified specific plasma proteins, for which a significant amount of variance could be explained by the experimental factors ‘sex’, ‘group’, ‘nausea’, or their interactions. GO enrichment analyses of these proteins identified ‘grooming behavior’ as a prominent hit, based on ‘neurexin-1’ (NRXN1) and ‘contactin-associated protein-like 4’ (CNTNAP4). Finally, Receiver Operator Characteristics (ROC) allowed to identify specific plasma proteins differentiating placebo responders from non-responders. These comprised immunoglobulins (IGHM, IGKV1D-16, IGHV3-23, IGHG1) and MASP2, related to regulation of complement activation, as well as proteins involved in oxidation reduction processes (QSOX1, CP TXN). This proof-of-concept study indicates that plasma proteomics are a promising tool to identify molecular correlates and predictors of the placebo effect in humans.
Improved daylight vision following AAV-mediated expression ofR9APin murine rod photoreceptors
Authors: Nishiguchi Koji M. , Fujita Kosuke , Cristante Enrico , Bainbridge James W. , Douglas Ronald H. , Nakazawa Toru , Smith Alexander J. , Ali Robin R. 
Published: February 2020

AbstractCone photoreceptors mediate daylight vision and are the primary cells responsible for vision in humans. Cone dysfunction leads to poor quality daylight vision because rod photoreceptors become saturated and non-functional at high light levels. Here we demonstrate that in mice lacking cone function, AAV-mediated over-expression of Rgs9-anchor protein (R9AP), a critical component of the GTPase complex that mediates the deactivation of the phototransduction cascade, results in desensitization of rod function and a “photopic shift” of the rod-driven electroretinogram. This treatment enables rods to respond to brighter light (up to ∼2.0 log) with increased visually-evoked cortical responses to high intensity stimulation. These results suggest that AAV-mediated transfer ofR9apinto rods might be used to improve daylight vision in humans visually handicapped by cone dysfunction.
Modeling microbial cross-feeding at intermediate scale portrays community dynamics and species coexistence
Authors: Liao Chen , Wang Tong , Maslov Sergei , Xavier Joao B. 
Published: February 2020

AbstractSocial interaction between microbes can be described at many levels of details: from the biochemistry of cell-cell interactions to the ecological dynamics of populations. Choosing an appropriate level to model microbial communities without losing generality remains a challenge. Here we show that modeling cross-feeding interactions at an intermediate level between genome-scale metabolic models of individual species and consumer-resource models of ecosystems is suitable to experimental data. We applied our modeling framework to three published examples of multi-strainEscherichia colicommunities with increasing complexity: uni-, bi-, and multi-directional cross-feeding of either substitutable metabolic byproducts or essential nutrients. The intermediate-scale model accurately fit empirical data and quantified metabolic exchange rates that are hard to measure experimentally, even for a complex community of 14 amino acid auxotrophies. By studying the conditions of species coexistence, the ecological outcomes of cross-feeding interactions, and each community’s robustness to perturbations, we extracted new quantitative insights from these three published experimental datasets. Our analysis provides a foundation to quantify cross-feeding interactions from experimental data, and highlights the importance of metabolic exchanges in the dynamics and stability of microbial communities.Author summaryThe behavior of microbial communities such as the human microbiome is hard to predict by its species composition alone. Our efforts to engineer microbiomes—for example to improve human health—would benefit from mathematical models that accurately describe how microbes exchange metabolites with each other and how their environment shapes these exchanges. But what is an appropriate level of details for those models? We propose an intermediate level to model metabolic exchanges between microbes. We show that these models can accurately describe population dynamics in three laboratory communities and predicts their stability in response to perturbations such as changes in the nutrients available in the medium that they grow on. Our work suggests that a highly detailed metabolic network model is unnecessary for extracting ecological insights from experimental data and improves mathematical models so that one day we may be able to predict the behavior of real-world communities such as the human microbiome.
Histo-molecular differentiation of renal cancer subtypes by mass spectrometry imaging and rapid proteome profiling of formalin-fixed paraffin-embedded tumor tissue sections
Authors: Möginger Uwe , Marcussen Niels , Jensen Ole N. 
Published: February 2020

AbstractPathology differentiation of renal cancer types is challenging due to tissue similarities or overlapping histological features of various tumor (sub)types. As assessment is often manually conducted outcomes can be prone to human error and therefore require high-level expertise and experience. Mass spectrometry can provide detailed histo-molecular information on tissue and is becoming increasingly popular in clinical settings. Spatially resolving technologies such as mass spectrometry imaging and quantitative microproteomics profiling in combination with machine learning approaches provide promising tools for automated tumor classification of clinical tissue sections.In this proof of concept study we used MALDI-MS imaging (MSI) and rapid LC-MS/MS-based microproteomics technologies (15 min/sample) to analyze formalin-fixed paraffin embedded (FFPE) tissue sections and classify renal oncocytoma (RO, n=11), clear cell renal cell carcinoma (ccRCC, n=12) and chromophobe renal cell carcinoma (ChRCC, n=5). Both methods were able to distinguish ccRCC, RO and ChRCC in cross-validation experiments. MSI correctly classified 87% of the patients whereas the rapid LC-MS/MS-based microproteomics approach correctly classified 100% of the patients.This strategy involving MSI and rapid proteome profiling by LC-MS/MS reveals molecular features of tumor sections and enables cancer subtype classification. Mass spectrometry provides a promising complementary approach to current pathological technologies for precise digitized diagnosis of diseases.