bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies
Authors: Demura Kanae , Kusakizako Tsukasa , Shihoya Wataru , Hiraizumi Masahiro , Nomura Kengo , Shimada Hiroto , Yamashita Keitaro , Nishizawa Tomohiro , Taruno Akiyuki , Nureki Osamu 
Published: February 2020

AbstractCalcium homeostasis modulator (CALHM) family proteins are Ca2+-regulated ATP-release channels involved in neural functions including neurotransmission in gustation. Here we present the cryo-EM structures of killifish CALHM1, human CALHM2, andC. elegansCLHM-1 at resolutions of 2.66, 3.51, and 3.60 Å, respectively. The CALHM1 octamer structure reveals that the N-terminal helix forms the constriction site at the channel pore in the open state, and modulates the ATP conductance. The CALHM2 undecamer and CLHM-1 nonomer structures show the different oligomeric stoichiometries among CALHM homologs. We further report the cryo-EM structures of the chimeric construct, revealing that the inter-subunit interactions at the transmembrane domain define the oligomeric stoichiometry. These findings advance our understanding of the ATP conduction and oligomerization mechanisms of CALHM channels.One Sentence SummaryCryo-EM structures reveal the ATP conduction and oligomeric assembly mechanisms of CALHM channels.
Hierarchical modeling of haplotype effects based on a phylogeny
Authors: Selle Maria Lie , Steinsland Ingelin , Lindgren Finn , Brajkovic Vladimir , Cubric-Curik Vlatka , Gorjanc Gregor 
Published: February 2020

AbstractThis paper introduces a hierarchical model to estimate haplotype effects based on phylogenetic relationships between haplotypes and their association with observed phenotypes. In a population there are usually many, but not all possible, distinct haplotypes and few observations per haplotype. Further, haplotype frequencies tend to vary substantially - few haplotypes have high frequency and many haplotypes have low frequency. Such data structure challenge estimation of haplotype effects. However, haplotypes often differ only due to few mutations and leveraging these similarities can improve the estimation of haplotype effects. There is extensive literature on this topic. Here we build on these observations and develop an autoregressive model of order one that hierarchically models haplotype effects by leveraging phylogenetic relationships between the haplotypes described with a directed acyclic graph. The phylogenetic relationships can be either in a form of a tree or a network and we therefore refer to the model as the haplotype network model. The haplotype network model can be included as a component in a phenotype model to estimate associations between haplotypes and phenotypes. The key contribution of this work is that by leveraging the haplotype network structure we obtain a sparse model and by using hierarchical autoregression the flow of information between similar haplotypes is estimated from the data. We show with a simulation study that the hierarchical model can improve estimates of haplotype effects compared to an independent haplotype model, especially when there are few observations for a specific haplotype. We also compared it to a mutation model and observed comparable performance, though the haplotype model has the potential to capture background specific effects. We demonstrate the model with a case study of modeling the effect of mitochondrial haplotypes on milk yield in cattle.
Glutamate and γ-aminobutyric acid differentially modulate glymphatic clearance of amyloid β through pulsation- and aquaporin-4 dependent mechanisms
Authors: Wu Cheng , Feng Yi-wei , Zhang Qun , Liang Feng-yin , Lan Yue , Pei Zhong , Xu Guang-qing 
Published: February 2020

AbstractThe glymphatic system contributes to a large proportion of brain waste clearance, including removal of amyloid β (Aβ). We have demonstrated that glutamate and γ-aminobutyric acid (GABA) influence glymphatic clearance through distinct mechanisms whereby GABA exerts modulatory effects in an aquaporin-4 (AQP4)-dependent manner while the actions of glutamate are pulsation-dependent. The efficacy of GABA and glutamate in alleviating Aβ in APP-PS1 and Angiotensin-II (Ang-II) induced hypertension mouse models was further evaluated. Notably, increasing GABA or inhibiting glutamate levels led to reduced binding of Aβ to pre-labeled plaques to similar extents in APP-PS1 mice while GABA appeared more efficient in Aβ clearance in hypertensive animals than the glutamate inhibitor. Our findings support the modulation of neurotransmitters that influence the glymphatic pathway via distinct mechanisms as a potentially effective therapeutic strategy for clearance of Aβ deposits from the brain.
Field and mesocosm methods to test biodegradable plastic film under marine conditions
Authors: Lott Christian , Eich Andreas , Unger Boris , Makarow Dorothée , Battagliarin Glauco , Schlegel Katharina , Lasut Markus T. , Weber Miriam 
Published: February 2020

AbstractThe pollution of the natural environment, especially the world’s oceans, with conventional plastic is of major concern. Biodegradable plastics are an emerging market bringing along potential chances and risks. The fate of these materials in the environment and their possible effects on organisms and ecosystems has rarely been studied systematically and is not well understood. For the marine environment, reliable field test methods and standards for assessing and certifying biodegradation to bridge laboratory respirometric data are lacking. In this work we present newly developed field tests to assess the performance of (biodegradable) plastics under natural marine conditions. These methods were successfully applied and validated in three coastal habitats (eulittoral, benthic and pelagic) and two climate zones (Mediterranean Sea and tropical Southeast Asia). Additionally, a stand-alone mesocosm test system which integrated all three habitats in one technical system at 400-L scale independent from running seawater is presented as a methodological bridge. Films of polyhydroxyalkanoate copolymer (PHA) and low density polyethylene (LD-PE) were used to validate the tests. While LD-PE remained intact, PHA disintegrated to a varying degree depending on the habitat and the climate zone. Together with the existing laboratory standard test methods, the field and mesocosm test systems presented in this work provide a 3-tier testing scheme for the reliable assessment of the biodegradation of (biodegradable) plastic in the marine environment. This toolset of tests can be adapted to other aquatic ecosystems.
Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden
Authors: Hillary Robert F. , Stevenson Anna J. , McCartney Daniel L. , Campbell Archie , Walker Rosie M. , Howard David M. , Ritchie Craig W. , Horvath Steve , Hayward Caroline , McIntosh Andrew M. , Porteous David J. , Deary Ian J. , Evans Kathryn L. , Marioni Riccardo E. 
Published: February 2020

AbstractIndividuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These include methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). In this study, we test the association between these epigenetic markers of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries. Furthermore, we test the clocks’ relationships with phenotypic measures associated with these conditions, including spirometric and biochemical traits. We carry out these analyses in 9,537 individuals from the Generation Scotland: Scottish Family Health Study. We find that DNAm GrimAge outperforms other epigenetic clocks in its associations with self-report disease prevalence and related clinical traits. DNAm GrimAge associates with chronic obstructive pulmonary disease (COPD) prevalence (Odds Ratio = 3.29, P = 3.0 × 10-4) and pulmonary spirometry tests (β = [-0.10 to −0.15], P = [1.4 × 10-4to 1.4 × 10-6]) at study baseline after adjusting for possibly confounding risk factors including alcohol, body mass index, deprivation, education and smoking. After adjusting for these confounding risk factors, DNAm GrimAge, DNAm PhenoAge and DNAm Telomere Length, measured at study baseline, predict incidence of ICD-10-coded disease states including COPD, type 2 diabetes and cardiovascular disease after thirteen years of follow-up (Hazard Ratios = [0.80 (telomere length) to 2.19 (GrimAge)], P = [9.9 × 10-4, 1.9 × 10-14]). Our data show that despite accounting for several possible confounding variables, epigenetic markers of ageing predict incidence of common disease. This may have significant implications for their potential utility in clinical settings to complement gold-standard methods of clinical assessment and management.
Contrasting species functional trait structuring of subarctic versus subtropical copepod communities
Authors: García-Comas Carmen , Hsieh Chih-hao , Chiba Sanae , Sugisaki Hiroya , Hashioka Taketo , Smith S. Lan 
Published: February 2020

ABSTRACTClassic niche theory assumes that species-level functional traits affect species relative fitness and thus community structuring, but empirical tests of this assumption are scarce. Moreover, recent evidence shows increasing functional over-redundancy towards the tropics, suggesting that the extent to which functional traits confer species’ fitness and thus impact community structuring differs across latitudes. Here, we develop a new method: comparing the frequencies of trait categories in the species-rank abundance distributions of local communities versus their frequencies in the regional average species pool. We contrasted subarctic versus subtropical copepod communities for six important traits. In subarctic communities, medium-sized and cold-water species are selected to dominate, thus traits affect relative fitness as predicted by classic niche theory. In subtropical communities, most species are small and warm-water, but these categories are not selected to dominate, suggesting that greater diversity towards the tropics results from lesser trait-based fitness differences allowing more species to coexist.
A tentacle for every occasion: comparing the hunting tentacles and sweeper tentacles, used for territorial competition, in the coralGalaxea fascicularis
Authors: Yosef Oshra , Popovits Yotam , Malik Assaf , Ofek-Lalzer Maya , Mass Tali , Sher Daniel 
Published: February 2020

AbstractCoral reefs are among the most diverse, complex and densely populated marine ecosystems. To survive, morphologically simple and sessile cnidarians have developed mechanisms to catch prey, deter predators and compete with adjacent corals for space, yet the mechanisms underlying these functions are largely unknown. Here, we characterize the histology, toxic activity and gene expression patterns in two different types of tentacles from the scleractinian coralGalaxea fascilcularis– catch tentacles (CTs), used to catch prey and deter predators, and sweeper tentacles (STs), specialized tentacles used for territorial aggression. STs exhibit more mucocytes and higher expression of mucin genes than CTs, and lack the ectodermal cilia used to deliver food to the mouth and remove debris. STs and CTs also express different sensory g-protein coupled receptors, suggesting they may employ different sensory pathways. Each tentacle type has a different complement of stinging cells (nematocytes), and the expression in the two tentacles of genes encoding structural nematocyte proteins suggests the stinging cells develop within the tentacles. CTs have higher neurotoxic and hemolytic activities, consistent with a role in prey capture, whereas the STs have higher phospholipase A2 activity, which we speculate may have a role in inducing tissue damage during territorial aggression. The toxin genes expressed in each tentacle are also different. These results show that the same organism utilizes two distinct tentacle types, each equipped with a different venom apparatus and toxin composition, for prey capture and defense and for territorial aggression.
The McGill-Mouse-Marmoset Platform: A Standardized Approach for High-throughput Imaging of Neuronal Dynamics During Behavior
Authors: Mosser Coralie-Anne , Haqqee Zeeshan , Nieto-Posadas Andres , Murai Keith , Stifani Stefano , Williams Sylvain , Brandon Mark P. 
Published: February 2020

AbstractUnderstanding the rules that govern neuronal dynamics throughout the brain to subserve behavior and cognition remain one of the biggest challenges in neuroscience research. Recent technical advances enable the recording of increasingly larger neuronal populations to produce increasingly more sophisticated datasets. Despite bold and important open-science and data-sharing policies, these datasets tend to include unique data acquisition methods, behavior, and file structures. Discrepancies between experimental protocols present several key challenges including the analysis of the data itself, comparison of data collected between laboratories, and for the comparison of dynamics between brain regions and species. Here, we discuss our recent efforts to create a standardized and high-throughput research platform to address these issues. The McGill-Mouse-Marmoset (M3) platform combines miniscope calcium imaging recording in both mice and marmosets with standardized touchscreen-based behavioral testing. The goal is to curate an open-source and standardized framework for acquiring, analyzing, and accessing high-quality data of the neuronal dynamics that underly cognition throughout the brain in mice, marmosets, and models of disease. We end with a discussion of future developments and a call for users to adopt this standardized approach.
Anacardic acid protects against phenylephrine-induced mouse cardiac hypertrophy through JNK signaling-dependent regulation of histone acetylation
Authors: Peng Bohui , Peng Chang , Luo Xiaomei , Huang Lixin , Mao Qian , Zhang Huanting , Han Xiao 
Published: February 2020

AbstractCardiac hypertrophy is a complex process induced by the activation of multiple signaling pathways. We previously reported that anacardic acid (AA), a histone acetylase (HAT) inhibitor, attenuates phenylephrine (PE)-induced cardiac hypertrophy by downregulating histone H3 acetylation at lysine 9 (H3K9ac). Unfortunately, the upstream signaling events remained unknown. The mitogen-activated protein kinase (MAPK) pathway is an important regulator of cardiac hypertrophy. In this study, we explored the role of JNK/MAPK signaling in cardiac hypertrophy. A mouse model of cardiomyocyte hypertrophy was successfully establishedin vitrousing PE. This study showed that p-JNK directly interacts with HATs (P300 and P300/CBP-associated factor, PCAF) and alters H3K9ac. In addition, both the JNK inhibitor SP600125 and the HAT inhibitor AA attenuated p-JNK overexpression and H3K9 hyperacetylation by inhibiting P300 and PCAF during PE-induced cardiomyocyte hypertrophy. Moreover, we demonstrated that both SP600125 and AA attenuate the overexpression of cardiac hypertrophy-related genes (MEF2A, ANP, BNP, andβ-MHC), preventing cardiomyocyte hypertrophy and dysfunction. These results revealed a novel mechanism through which AA might protect mice from PE-induced cardiac hypertrophy. In particular, AA inhibits the effects of JNK signaling on HAT-mediated histone acetylation, and could therefore be used to prevent and treat hypertrophic cardiomyopathy.
A Pre-computed Probabilistic Molecular Search Engine for Tandem Mass Spectrometry Proteomics
Authors: Jones Jeff 
Published: February 2020

AbstractMass spectrometry methods of peptide identification involve comparing observed tandem spectra within-silicoderived spectrum models. Presented here is a proteomics search engine that offers a new variation of the standard approach, with improved results. The proposed method employs information theory and probabilistic information retrieval on a pre-computed and indexed fragmentation database generating a peptide-to-spectrum match (PSM) score modeled on fragment ion frequency. As a result, the direct application of modern document mining, allows for treating the collection of peptides as a corpus and corresponding fragment ions as indexable words, leveraging ready-built search engines and common predefined ranking algorithms. Fast and accurate PSM matches are achieved yielding a 5-10% higher rate of peptide identities than current database mining methods. Immediate applications of this search engine are aimed at identifying peptides from large sequence databases consisting of homologous proteins with minor sequence variations, such as genetic variation expected in the human population.
PhISCS-BnB: A Fast Branch and Bound Algorithm for the Perfect Tumor Phylogeny Reconstruction Problem
Authors: Sadeqi Azer Erfan , Rashidi Mehrabadi Farid , Li Xuan Cindy , Malikić Salem , Schäffer Alejandro A. , Gertz E. Michael , Day Chi-Ping , Pérez-Guijarro Eva , Marie Kerrie , Lee Maxwell P. , Merlino Glenn , Ergun Funda , Sahinalp S. Cenk 
Published: February 2020

AbstractMotivationRecent advances in single cell sequencing (SCS) offer an unprecedented insight into tumor emergence and evolution. Principled approaches to tumor phylogeny reconstruction via SCS data are typically based on general computational methods for solving an integer linear program (ILP), or a constraint satisfaction program (CSP), which, although guaranteeing convergence to the most likely solution, are very slow. Others based on Monte Carlo Markov Chain (MCMC) or alternative heuristics not only offer no such guarantee, but also are not faster in practice. As a result, novel methods that can scale up to handle the size and noise characteristics of emerging SCS data are highly desirable to fully utilize this technology.ResultsWe introduce PhISCS-BnB, a Branch and Bound algorithm to compute the most likely perfect phylogeny (PP) on an input genotype matrix extracted from a SCS data set. PhISCS-BnB not only offers an optimality guarantee, but is also 10 to 100 times faster than the best available methods on simulated tumor SCS data. We also applied PhISCS-BnB on a large melanoma data set derived from the sub-lineages of a cell line involving 24 clones with 3574 mutations, which returned the optimal tumor phylogeny in less than 2 hours. The resulting phylogeny also agrees with bulk exome sequencing data obtained fromin vivotumors growing out from the same cell line.Availabilityhttps://github.com/algo-cancer/PhISCS-BnB
The term structure of equity factor diversification
Authors: Fouquau Julien , Kharoubi Cecile 
Published: February 2020

Purpose
Risk factor investing has grown in popularity in recent years and has become a cornerstone of investment portfolios. The goal of factor investing is to generate more returns in the long run. This paper aims to studies the term structure of equity factor. The authors consider the point of view of an American investor and use risk, diversification and performance measures.

Design/methodology/approach
The authors combine two methodologies as follows: wavelets and copulas. The authors use daily, weekly and monthly equity factor returns to calibrate wavelets and copulas. Copula functions are useful instruments to describe “joint” fluctuations in different markets, especially to capture nonlinearities, providing a reasonable alternative to the assumption of joint normality. To check robustness, the authors propose three different wavelet mother functions to decompose the data and three different time horizons and the authors add a complementary exercise based on performance and diversification measurement without wavelet transform.

Findings
The authors identify temporal horizons for which diversification benefits would be optimized with the decrease in the level of dependence or even the inversion of the dependence structure. Thus, investors seeking diversification with factor investing have to care about the considered horizon: size and book to market factors seem to provide better diversification in the short term. Momentum strategies seem to deliver better diversification in the long run. All the results are very consistent.

Originality/value
Very few papers have documented the diversification properties of the equity risk factors. While factors are built to capture systematic risk premia, their diversification properties are still poorly understood. It is necessary to take into account non-normality of risk factors and to study the diversification over different time horizons. The solution is to use wavelet methodology to decompose returns into temporal series of different maturities.
Does securitization escalate banks’ sensitivity to systemic risk?
Authors: Ivanov Katerina , Jiang Julia 
Published: February 2020

PurposeThe purpose of this paper is to test empirically the impact of asset securitization and sale activities as well as the holdings of sub-prime related securitized products on the US bank holding companies’ (BHC) exposure to systemic risk.Design/methodology/approachThis paper adopts a robust econometric method to estimate the conditional value-at-risk as a measure of BHCs' institutional sensitivity to market crushes. Using the data over the period of 2004-2016, the study also uses OLS with robust standard errors and panel estimation with random effects as two alternative estimation techniques to assess the impact of securitization activities on the sensitivity of BHCs to systemic risk.FindingsResidential mortgage and other forms of securitization activities are positively related to an increase in the US BHCs' sensitivity to systemic distress. The significant cross effects of both securitized loans and holdings of securitized products play a crucial role in determining risks in financial sector.Originality/valueThis study contributes to the empirical literature on the effects of securitization on BHCs' risk exposures in several ways. First, the paper considers the complexity of the bank's risk profile; it focuses on BHCs' individual sensitivity to systemic distress and its dependence on the size of securitization and assets sold activities considering both supply and demand sides of securitization. Second, the time horizon under investigation sheds a light on the relationship between securitization and banks' risk exposures including the pre-crisis, crisis and post-crisis periods.
Presentation of a school of government model through a comparative study of selected schools
Authors: Abdolhosseinzadeh Mohammad , Abdolhamid Mahdi 
Published: February 2020

Purpose
The purpose of this paper is to promote governance quality by presenting a school of government model.

Design/methodology/approach
To this end, seven schools were selected from among 25 outstanding existing schools of government by purposive sampling. Subsequently, these schools were carefully examined and categorized into primary and support processes through a comparative study and the categorical content analysis approach.

Findings
The resulting four primary processes of education, research and agenda-setting, discourse-making and networking, and training and cadre-building, and the five sub-systems of schools of government were extracted. The outputs of the school of government model were classified into the three categories of training cadres experienced in public policy and administration, discourse-making and influencing the environment and theorizing. Finally, the extracted categories were approved by the relevant experts through the fuzzy Delphi method.

Originality/value
This paper can contribute to the training of policymakers and policy researchers, as well as to the establishment, and more effective management, of schools of government.