bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraining the fraction of core-collapse supernovae harbouring choked jets with high-energy neutrinos
Authors: Guetta Dafne , Rahin Roi , Bartos Imre , Della Valle Massimo 
Published: January 2020

ABSTRACT
The joint observation of core-collapse supernovae with gamma-ray bursts shows that jets can be launched in the aftermath of stellar core collapse, likely by a newly formed black hole that accretes matter from the star. Such gamma-ray bursts have only been observed accompanying Type Ibc supernovae, indicating a stellar progenitor that lost its hydrogen envelope before collapse. According to recent hypothesis, it is possible that jets are launched in core-collapse events even when the progenitors still retain their hydrogen envelopes; however, such jets are not able to burrow through the star and will be stalled into the interior of the progenitor star before escaping. These jets are called choked jets. High-energy neutrinos produced by such choked jets could escape the stellar envelope and could be observed. Here, we examine how multimessenger searches for high-energy neutrinos and core-collapse supernovae can detect or limit the fraction of stellar collapses that produce jets. We find that a high fraction of jet production is already limited by previous observational campaigns. We explore possibilities with future observations using Large Synoptic Survey Telescope, IceCube, and Km3NET.
Ancient DNA Evidence from China Reveals the Expansion of Pacific Dogs
Authors: Zhang Ming , Sun Guoping , Ren Lele , Yuan Haibing , Dong Guanghui , Zhang Lizhao , Liu Feng , Cao Peng , Ko Albert Min-Shan , Yang Melinda A , Hu Songmei , Wang Guo-Dong , Fu Qiaomei 
Published: January 2020

Abstract
The ancestral homeland of Australian dingoes and Pacific dogs is proposed to be in South China. However, the location and timing of their dispersal and relationship to dog domestication is unclear. Here, we sequenced 7,000- to 2,000-year-old complete mitochondrial DNA (mtDNA) genomes of 27 ancient canids (one gray wolf and 26 domestic dogs) from the Yellow River and Yangtze River basins (YYRB). These are the first complete ancient mtDNA of Chinese dogs from the cradle of early Chinese civilization. We found that most ancient dogs (18/26) belong to the haplogroup A1b lineage that is found in high frequency in present-day Australian dingoes and precolonial Pacific Island dogs but low frequency in present-day China. Particularly, a 7,000-year-old dog from the Tianluoshan site in Zhejiang province possesses a haplotype basal to the entire haplogroup A1b lineage. We propose that A1b lineage dogs were once widely distributed in the YYRB area. Following their dispersal to South China, and then into Southeast Asia, New Guinea and remote Oceania, they were largely replaced by dogs belonging to other lineages in the last 2,000 years in present-day China, especially North China.
Developmental biology meets toxicology: contributing reproductive mechanisms to build adverse outcome pathways
Authors: Draskau Monica Kam , Spiller Cassy M , Boberg Julie , Bowles Josephine , Svingen Terje 
Published: January 2020

Abstract
An adverse outcome pathway (AOP) is a simplified description of the sequence of mechanistic events that lead to a particular toxicological effect, from initial trigger to adverse outcome. Although designed to inform regulatory risk assessors, the AOP framework also provides a platform for innovative collaborations between experts from relevant research fields and the regulatory community. The underpinning for any AOP is basic knowledge about molecular and developmental processes; such knowledge can only be attained by solid bioscientific research. Starting with this fundamental knowledge, the objective is to devise novel testing strategies that focus on key events in a causative pathway. It is anticipated that such a knowledge-based approach will ultimately alleviate many of the burdens associated with classical chemical testing strategies that typically involve large-scale animal toxicity regimens. This hails from the notion that a solid understanding of the underlying mechanisms will allow the development and use of alternative test methods, including both in vitro and in silico approaches. This review is specifically targeted at professionals working in bioscientific fields, such as developmental and reproductive biology, and aims to (i) inform on the existence of the AOP framework and (ii) encourage new cross-disciplinary collaborations. It is hoped that fundamental biological knowledge can thus be better exploited for applied purposes: firstly, an improved understanding of how our perpetual exposure to environmental chemicals is causing human reproductive disease and, secondly, new approaches to screen for harmful chemicals more efficiently. This is not an instructional manual on how to create AOPs; rather, we discuss how to harness fundamental knowledge from the biosciences to assist regulatory toxicologists in their efforts to protect humans against chemicals that harm human reproductive development and function.
Anticipatory-Vicarious Grief: The Anatomy of a Moral Emotion
Authors: Varga Somogy , Gallagher Shaun 
Published: January 2020

AbstractGrief is often described as characterized by a particular emotional response to another person’s death. While this is true of paradigm cases, we argue that a broader notion of grief allows accommodating forms of this emotional experience that deviate from the paradigmatic case. The bulk of the paper explores such a nonparadigmatic form of grief, anticipatory-vicarious grief (AV-grief), which is typically triggered by pondering the inevitability of our own death. We argue that AV-grief is a particular moral emotion that serves a unique function and is indissolubly linked to the practical identities of human agents. An agent’s AV-grief is about the harm that occurs to individuals whose practical identities depend on the agent.
rRNA expansion segment 27Lb modulates the factor recruitment capacity of the yeast ribosome and shapes the proteome
Authors: Shankar Vaishnavi , Rauscher Robert , Reuther Julia , Gharib Walid H , Koch Miriam , Polacek Norbert 
Published: January 2020

Abstract
Fine-tuned regulation of protein biosynthesis is crucial for cellular fitness and became even more vital when cellular and organismal complexity increased during the course of evolution. In order to cope with this augmented demand for translation control, eukaryal ribosomes have gained extensions both at the ribosomal protein and rRNA levels. Here we analyze the functional role of ES27L, an rRNA expansion segment in the large ribosomal subunit of Saccharomyces cerevisiae. Deletion of the b-arm of this expansion segment, called ES27Lb, did not hamper growth during optimal conditions, thus demonstrating that this 25S rRNA segment is not inherently crucial for ribosome functioning. However, reductive stress results in retarded growth and rendered unique protein sets prone to aggregation. Lack of ES27Lb negatively affects ribosome-association of known co-translational N-terminal processing enzymes which in turn contributes to the observed protein aggregation. Likely as a compensatory response to these challenges, the truncated ribosomes showed re-adjusted translation of specific sets of mRNAs and thus fine-tune the translatome in order to re-establish proteostasis. Our study gives comprehensive insight into how a highly conserved eukaryal rRNA expansion segment defines ribosomal integrity, co-translational protein maturation events and consequently cellular fitness.
SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair
Authors: Hou Tianyun , Cao Ziyang , Zhang Jun , Tang Ming , Tian Yuan , Li Yinglu , Lu Xiaopeng , Chen Yongcan , Wang Hui , Wei Fu-Zheng , Wang Lina , Yang Yang , Zhao Ying , Wang Zimei , Wang Haiying , Zhu Wei-Guo 
Published: January 2020

Abstract
Genomic instability is an underlying hallmark of cancer and is closely associated with defects in DNA damage repair (DDR). Chromatin relaxation is a prerequisite for DDR, but how chromatin accessibility is regulated remains elusive. Here we report that the histone deacetylase SIRT6 coordinates with the chromatin remodeler CHD4 to promote chromatin relaxation in response to DNA damage. Upon DNA damage, SIRT6 rapidly translocates to DNA damage sites, where it interacts with and recruits CHD4. Once at the damage sites, CHD4 displaces heterochromatin protein 1 (HP1) from histone H3 lysine 9 trimethylation (H3K9me3). Notably, loss of SIRT6 or CHD4 leads to impaired chromatin relaxation and disrupted DNA repair protein recruitment. These molecular changes, in-turn, lead to defective homologous recombination (HR) and cancer cell hypersensitivity to DNA damaging agents. Furthermore, we show that SIRT6-mediated CHD4 recruitment has a specific role in DDR within compacted chromatin by HR in G2 phase, which is an ataxia telangiectasia mutated (ATM)-dependent process. Taken together, our results identify a novel function for SIRT6 in recruiting CHD4 onto DNA double-strand breaks. This newly identified novel molecular mechanism involves CHD4-dependent chromatin relaxation and competitive release of HP1 from H3K9me3 within the damaged chromatin, which are both essential for accurate HR.
Dickkopf 3—a novel biomarker of the ‘kidney injury continuum’
Authors: Schunk Stefan J , Speer Thimoteus , Petrakis Ioannis , Fliser Danilo 
Published: January 2020

Abstract
Chronic kidney disease (CKD) is a global public health problem accompanied by substantial comorbidities and reduced life expectancy. In this respect, progressive CKD leading to uraemia can be seen as a systemic disease with a critical impact on virtually all organ systems. Therefore, it is of particular importance to identify patients with ongoing CKD progression, which is challenging, because the individual course of CKD is difficult to predict. Patterns of progression in CKD patients include linear and non-linear trajectories of GFR loss, but kidney function can also remain stable for years. Moreover, a substantial GFR decline may occur in the absence of higher-grade albuminuria (non-proteinuric CKD), rendering the measurement of albuminuria less reliable for progression prediction in such individuals. In the present review, we focus on the recently identified glycoprotein Dickkopf-3 (DKK3) as a stress-induced, renal tubular epithelial cell-derived, pro-fibrotic molecule. In experimental CKD models, DKK3 promoted renal tubulointerstitial fibrosis through modulation of the canonical Wnt/β-catenin signalling pathway. In clinical studies, increased urinary DKK3 levels identified patients at high risk for short-term CKD progression, regardless of the cause of kidney disease, baseline kidney function and albuminuria. Moreover, increased urinary DKK3 levels are associated with a high risk for acute kidney injury and the subsequent loss of kidney function after cardiac surgery. These findings highlight DKK3 as a mediator of renal tubular cell damage in kidney injury and short-term progression of kidney disease, with potential therapeutic implications.
Land-surface processes and summer-cloud-precipitation characteristics in the Tibetan Plateau and their effects on downstream weather: a review and perspective
Authors: Fu Yunfei , Ma Yaoming , Zhong Lei , Yang Yuanjian , Guo Xueliang , Wang Chenghai , Xu Xiaofeng , Yang Kun , Xu Xiangde , Liu Liping , Fan Guangzhou , Li Yueqing , Wang Donghai 
Published: January 2020

AbstractCorrect understanding of the land-surface processes and cloud-precipitation processes in the Tibetan Plateau (TP) is an important prerequisite for the study and forecast of the downstream activities of weather systems and one of the key points for understanding the global atmospheric movement. In order to show the achievements that have been made, this paper reviews the progress on the observations for the atmospheric boundary layer, land-surface heat fluxes, cloud-precipitation distributions and vertical structures by using ground- and space-based multiplatform, multisensor instruments and the effect of the cloud system in the TP on the downstream weather. The results show that the form drag related to the topography, land–atmosphere momentum and scalar fluxes is an important part of the parameterization process. The sensible heat flux decreased especially in the central and northern TP caused by the decrease in wind speeds and the differences in the ground-air temperatures. Observations show that the cloud and precipitation over the TP have a strong diurnal variation. Studies also show the compressed-air column in the troposphere by the higher-altitude terrain of the TP makes particles inside clouds vary at a shorter distance in the vertical direction than those in the non-plateau area so that precipitation intensity over the TP is usually small with short duration, and the vertical structure of the convective precipitation over the TP is obviously different from that in other regions. In addition, the influence of the TP on severe weather downstream is preliminarily understood from the mechanism. It is necessary to use model simulations and observation techniques to reveal the difference between cloud precipitation in the TP and non-plateau areas in order to understand the cloud microphysical parameters over the TP and the processes of the land boundary layer affecting cloud, precipitation and weather in the downstream regions.
A Retrospective Analysis and Comparison of the STAM and STAMCO Classification and EAONO/JOS Cholesteatoma Staging System in Predicting Surgical Treatment Outcomes of Middle Ear Cholesteatoma
Authors: van der Toom HFE , van der Schroeff MP , Janssen JMH , Westzaan AM , Pauw RJ 
Published: January 2020

Objective:
To evaluate and compare the STAM classification, STAMCO classification and the EAONO/JOS staging system as predictors for cholesteatoma recidivism and postoperative hearing, using a large patient cohort in our tertiary referral center.

Method:
Two hundred thirty-one patients who underwent surgery for primary cholesteatoma between 2003 and December 2012 were included and retrospectively classified and staged according to the STAM classification, STAMCO classification, and EAONO/JOS staging system. Data on cholesteatoma recidivism rates and postoperative hearing were collected. The predictive value of the three instruments for recurrent and residual cholesteatoma was compared by using receiver operating characteristic curves.

Results:
For predicting recurrent cholesteatoma, the STAMCO classification was significantly superior compared to the other two instruments. For predicting residual cholesteatoma, the STAMCO classification was superior to the EANO/JOS Staging system. The postoperative hearing shows a significant increase in ABG with increasing extension of cholesteatoma in the CWU group and a significant decrease in AC threshold level with increasing stage and a significant increase in AC with increasing ossicular chain status in the CWD group.

Conclusion:
Based on our study, the STAMCO classification represents the best available predictor for recurrent cholesteatoma and holds most promise for predicting residual cholesteatoma. Extension of cholesteatoma seems to be linked to postoperative hearing and thus the classifications and staging systems may be able to predict postoperative hearing. More studies are needed to assess the validation of these classifications.
Sensitive detection of tumor mutations from blood and its application to immunotherapy prognosis
Authors: Li Shuo , Noor Zorawar , Zeng Weihua , Ni Xiaohui , Yuan Zuyang , Alber Frank , Li Wenyuan , Garon Edward B. , Zhou Xianghong Jasmine 
Published: January 2020

AbstractLiquid biopsy using cell-free DNA (cfDNA) is attractive for a wide range of clinical applications, including cancer detection, locating, and monitoring. However, developing these applications requires precise and sensitive calling of somatic single nucleotide variations (SNVs) from cfDNA sequencing data. To date, no SNV caller addresses all the special challenges of cfDNA to provide reliable results. Here we present cfSNV, a revolutionary somatic SNV caller with five innovative techniques to overcome and exploit the unique properties of cfDNA. cfSNV provides hierarchical mutation profiling, thanks to cfDNA’s complete coverage of the clonal landscape, and multi-layer error suppression. In both simulated datasets and real patient data, we demonstrate that cfSNV is superior to existing tools, especially for low-frequency somatic SNVs. We also show how the five novel techniques contribute to its performance. Further, we demonstrate a clinical application using cfSNV to select non-small-cell lung cancer patients for immunotherapy treatment.
FGFR3 is a positive regulator of osteoblast expansion and differentiation during zebrafish skull vault development
Authors: Dambroise Emilie , Ktorza Ivan , Brombin Alessandro , Abdessalem Ghaith , Edouard Joanne , Luka Marine , Fiedler Imke , Binder Olivia , Pelle Olivier , Patton E. Elizabeth , Busse Björn , Menager Mickaël , Sohm Frederic , Legeai-Mallet Laurence 
Published: January 2020

AbstractGain- or loss-of-function mutations in fibroblast growth factor receptor 3 (FGFR3) result in cranial vault defects - highlighting the protein’s role in membranous ossification. Zebrafish express high levels offgfr3during skull development; in order to study FGFR3’s role in cranial vault development, we generated the firstfgfr3loss-of-function zebrafish(fgfr3lof/lof). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. Integrated analyses (in vivoimaging, and single-cell RNA sequencing of the osteoblast lineage) of zebrafishfgfr3lof/lofrevealed a delay in osteoblast expansion and differentiation, together with changes in the extracellular matrix. These findings demonstrate thatfgfr3is a positive regulator of osteogenesis. We hypothesize that changes in the extracellular matrix within growing bone impair cell-cell communication, mineralization, and new osteoblast recruitment.
Improving the informativeness of Mendelian disease-derived pathogenicity scores for common disease
Authors: Kim Samuel S. , Dey Kushal K. , Weissbrod Omer , Marquez-Luna Carla , Gazal Steven , Price Alkes L. 
Published: January 2020

AbstractDespite considerable progress on pathogenicity scores prioritizing both coding and noncoding variants for Mendelian disease, little is known about the utility of these pathogenicity scores for common disease. Here, we sought to assess the informativeness of Mendelian diseasederived pathogenicity scores for common disease, and to improve upon existing scores. We first applied stratified LD score regression to assess the informativeness of annotations defined by top variants from published Mendelian disease-derived pathogenicity scores across 41 independent common diseases and complex traits (averageN= 320K). Several of the resulting annotations were informative for common disease, even after conditioning on a broad set of coding, conserved, regulatory and LD-related annotations from the baseline-LD model. We then improved upon the published pathogenicity scores by developing AnnotBoost, a gradient boosting-based framework to impute and denoise pathogenicity scores using functional annotations from the baseline-LD model. AnnotBoost substantially increased the informativeness for common disease of both previously uninformative and previously informative pathogenicity scores, implying pervasive variant-level overlap between Mendelian disease and common disease. The boosted scores also produced significant improvements in heritability model fit and in classifying disease-associated, fine-mapped SNPs. Our boosted scores have high potential to improve candidate gene discovery and fine-mapping for common disease.
Hepatic Mitochondrial Remodeling is Mechanistically Linked to Insulin Resistance in Nonalcoholic Fatty Liver Disease
Authors: Shannon Chris E. , Ragavan Mukundan , Palavicini Juan Pablo , Fourcaudot Marcel , Bakewell Terry , Jin Eunsook S. , Madesh Muniswamy , Malloy Craig R. , Han Xianlin , Merritt Matthew E. , Norton Luke 
Published: January 2020

ABSTRACTInsulin resistance and altered hepatic mitochondrial function are central features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), but the etiological role of these processes in disease progression remains unclear. We investigated the molecular links between insulin resistance, mitochondrial remodeling, and hepatic lipid accumulation in a rodent model of T2D / NAFLD. Livers from obese, insulin resistant mice displayed augmented mitochondrial content and increased TCA cycle and pyruvate dehydrogenase (PDH) activities. Insulin sensitization with pioglitazone mitigated pyruvate-driven TCA cycle activity and PDH activation via both covalent (PDK4 and PDP2) and allosteric (intracellular pyruvate availability) mechanisms. Interestingly, improvements in insulin sensitivity and mitochondrial function were entirely dissociated from changes in hepatic triglycerides, diacylglycerides or fatty acids. Instead, we show that the mitochondrial phospholipid cardiolipin undergoes pathological remodeling in livers from obese mice and that this is reversed by insulin sensitization. Our findings identify targetable mitochondrial features of T2D and NAFLD and highlight the benefit of insulin sensitization in managing the clinical burden of obesity-associated disease.
Community lifespan, niche expansion and the evolution of interspecific cooperation
Authors: Rodrigues António M. M. , Estrela Sylvie , Brown Sam P. 
Published: January 2020

AbstractNatural selection favours individuals who maximise their own reproductive success and that of their close relatives. From this perspective, cooperation that benefits individuals of a different species represents an evolutionary conundrum. The theory of mutualism seeks to resolve this puzzle, and it posits that there must be downstream benefits to cooperators that offset any costs inherently associated with interspecific cooperation. Thus, individuals should only further the survival and fecundity of their interspecific partners if this generates additional return benefits, such as food, shelter or protection. A major challenge for the evolution of mutualism is when the ecological niches of partner species overlap, as this creates a tension between the benefits of exchanging services and the costs of competing for shared resources. Here we study the extent to which niche expansion, in which cooperation augments the common pool of resources, can resolve this problem. We find that niche expansion facilitates the evolution of mutualism, especially when populations are at high densities. Further, we show that niche expansion can promote the evolution of reproductive restraint, in which a focal species adaptively sacrifices its own growth rate to increase the density of partner species. We interpret these results in the context of microbial community interactions, which are often characterized by yield-enhancing exchanges of nutrients, termed ‘cross-feeding’. Our findings suggest that yield-enhancing mutualisms are more prevalent in stable habitats with a constant supply of resources, where populations typically live at high densities, but such mutualisms are particularly vulnerable to the emergence of cheats. In general, our findings highlight the need to integrate both temporal and spatial dynamics in the analysis of mutualisms.