bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Atlas of the Human Fovea and Peripheral Retina
Authors: Yan Wenjun , Peng Yi-Rong , van Zyl Tavé , Regev Aviv , Shekhar Karthik , Juric Dejan , Sanes Joshua R 
Published: February 2020

ABSTRACTMost irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ∼85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey,Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.
Statistics based predictions of coronavirus 2019-nCoV spreading in mainland China
Authors: Nesteruk Igor 
Published: February 2020

ABSTRACTBackgroundThe epidemic outbreak cased by coronavirus 2019-nCoV is of great interest to researches because of the high rate of spread of the infection and the significant number of fatalities. A detailed scientific analysis of the phenomenon is yet to come, but the public is already interested in the questions of the duration of the epidemic, the expected number of patients and deaths. For long time predictions, the complicated mathematical models are necessary which need many efforts for unknown parameters identification and calculations. In this article, some preliminary estimates will be presented.ObjectiveSince the reliable long time data are available only for mainland China, we will try to predict the epidemic characteristics only in this area. We will estimate some of the epidemic characteristics and present the most reliable dependences for victim numbers, infected and removed persons versus time.MethodsIn this study we use the known SIR model for the dynamics of an epidemic, the known exact solution of the linear equations and statistical approach developed before for investigation of the children disease, which occurred in Chernivtsi (Ukraine) in 1988-1989.ResultsThe optimal values of the SIR model parameters were identified with the use of statistical approach. The numbers of infected, susceptible and removed persons versus time were predicted.ConclusionsSimple mathematical model was used to predict the characteristics of the epidemic caused by coronavirus 2019-nCoV in mainland China. The further research should focus on updating the predictions with the use of fresh data and using more complicated mathematical models.
Distinct striatal subregions and corticostriatal connectivity for effort, action and reward
Authors: Suzuki Shosuke , Lawlor Victoria M. , Cooper Jessica A. , Arulpragasam Amanda R. , Treadway Michael T. 
Published: February 2020

AbstractThe ventral striatum is believed to encode the subjective value of cost/benefit options; however, this effect has strikingly been absent during choices that involve physical effort. Prior work in freely-moving animals has revealed opposing striatal signals, with greater response to increasing effort demands and reduced responses to rewards requiring effort. Yet, the relationship between these conflicting signals remains unknown. Using fMRI with a naturalistic, effort-based navigation paradigm, we identified functionally-segregated regions within ventral striatum that separately encoded action, effort, and discounting of rewards by effort. Strikingly, these sub-regions mirrored results from a large-sample connectivity-based parcellation of the striatum. Moreover, individual differences in striatal effort activation and effort discounting signals predicted striatal responses to effort-related choices during an independent fMRI task. Taken together, our results suggest that a dorsomedial region primarily associated with action may instead represent the effort cost of actions, and raises fundamental questions regarding the interpretation of striatal “reward” signals in the context of effort demands.
Human papillomavirus integration transforms chromatin to drive oncogenesis
Authors: Karimzadeh Mehran , Arlidge Christopher , Rostami Ariana , Lupien Mathieu , Bratman Scott V. , Hoffman Michael M. 
Published: February 2020

AbstractHuman papillomavirus (HPV) drives almost all cervical cancers and up to ∼70% of head and neck cancers. Frequent integration into the host genome occurs only for tumourigenic strains of HPV. We hypothesized that changes in the epigenome and transcriptome contribute to the tumourigenicity of HPV. We found that viral integration events often occurred along with changes in chromatin state and expression of genes near the integration site. We investigated whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF binding site, showed enriched chromatin accessibility signal. ChIP-seq revealed that the conserved CTCF binding site within the HPV genome bound CTCF in 4 HPV+cancer cell lines. Significant changes in CTCF binding pattern and increases in chromatin accessibility occurred exclusively within 100 kbp of HPV integration sites. The chromatin changes co-occurred with out-sized changes in transcription and alternative splicing of local genes. We analyzed the essentiality of genes upregulated around HPV integration sites of The Cancer Genome Atlas (TCGA) HPV+tumours. HPV integration upregulated genes which had significantly higher essentiality scores compared to randomly selected upregulated genes from the same tumours. Our results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin and upregulates genes essential for tumour viability in some HPV+tumours. These findings emphasize a newly recognized role of HPV integration in oncogenesis.
Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes
Authors: Wells Jennifer N. , Buschauer Robert , Mackens-Kiani Timur , Best Katharina , Kratzat Hanna , Berninghausen Otto , Becker Thomas , Gilbert Wendy , Cheng Jingdong , Beckmann Roland 
Published: February 2020

AbstractCells adjust to nutrient deprivation by reversible translational shut down. This is accompanied by maintaining inactive ribosomes in a hibernation state, where they are bound by proteins with inhibitory and protective functions. In eukaryotes, such a function was attributed to Stm1 (SERBP1 in mammals), and recently Lso2 (CCDC124 in mammals) was found to be involved in translational recovery after starvation from stationary phase. Here, we present cryo-electron microscopy (cryo-EM) structures of translationally inactive yeast and human ribosomes. We found Lso2/CCDC124 accumulating on idle ribosomes in the non-unrotated state, in contrast to Stm1/SERBP1-bound ribosomes, which display a rotated state. Lso2/CCDC124 bridges the decoding sites of the small with the GTPase-activating center of the large subunit. This position allows accommodation of the Dom34-dependent ribosome recycling system, which splits Lso2-containing but not Stm1-containing ribosomes. We propose a model in which Lso2 facilitates rapid translation reactivation by stabilizing the recycling-competent state of inactive ribosomes.
Myosin 18Aα targets guanine nucleotide exchange factor β-Pix to dendritic spines of cerebellar Purkinje neurons to promote spine maturation
Authors: Alexander Christopher J. , Barzik Melanie , Fujiwara Ikuko , Remmert Kirsten , Wang Ya-Xian , Petralia Ronald S. , Friedman Thomas B. , Hammer John A. 
Published: February 2020

ABSTRACTDendritic spines are signaling microcompartments that serve as the primary site of synapse formation in neurons. Actin assembly and myosin 2 contractility play major roles in the maturation of spines from filopodial precursors, as well as in the subsequent, activity-dependent changes in spine morphology that underly learning and memory. Myosin 18A is a myosin 2-like protein conserved from flies to man that lacks motor activity, is sub-stochiometric to myosin 2, and co-assembles with myosin 2 to make mixed filaments. Myosin 18A is alternatively spliced to create multiple isoforms that contain unique N- and C-terminal extensions harboring both recognizable and uncharacterized protein: protein interaction domains. These observations suggest that myosin 18A serves to recruit proteins to mixed filaments of myosin 2 and myosin 18A. One protein known to bind to myosin 18A is β-Pix, a guanine nucleotide exchange factor (GEF) for Rac1 and Cdc42. Notably, β-Pix has been shown to promote spine maturation by activating both Arp2/3 complex-dependent branched actin filament assembly and myosin 2 contractility within spines. Here we show that myosin 18Aα is expressed in cerebellar Purkinje neurons and concentrates in spines along with myosin 2 and F-actin. Myosin 18Aα is targeted to spines by co-assembling with myosin 2 and by an actin binding site present in its N-terminal extension. miRNA-mediated knockdown of myosin 18Aα results in a significant defect in spine maturation that is rescued by an RNAi-immune version of myosin 18Aα. Importantly, β-Pix co-localizes with myosin 18Aα in spines, and its spine localization is lost upon myosin 18Aα knockdown or when its myosin 18Aα binding site is deleted. Finally, we show that the spines of myosin 18Aα knockdown Purkinje neurons contain significantly less F-actin and myosin 2. Together, these data demonstrate that mixed filaments of myosin 2 and myosin 18Aα form a complex with β-Pix in Purkinje neuron spines that promotes spine maturation by enhancing the assembly of actin and myosin filaments downstream of β-Pix’s GEF activity.
DEG/ENaC/ASIC channels vary in their sensitivity to anti-hypertensive and non-steroidal anti-inflammatory drugs
Authors: Fechner S. , D’Alessandro I. , Wang L. , Tower C. , Tao L. , Goodman M.B. 
Published: February 2020

AbstractThe degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homomeric or heteromeric trimers. Based on studies of selected family members, these channels are assumed to form non-voltage gated and sodium-selective channels sensitive to the anti-hypertensive drug, amiloride. They are also emerging as a target of nonsteroidal anti-inflammatory drugs (NSAIDs).C. eleganshas more than two dozen genes encoding DEG/ENaC/ASIC subunits, providing an excellent opportunity to examine variations in drug sensitivity. Here, we analyze a subset of theC. elegansDEG/ENaC/ASIC proteins to test the hypothesis that individual family members vary not only in their ability to form homomeric channels, but also in their drug sensitivity. We selected fiveC. elegansDEG/ENaC/ASICs (DEGT-1, DEL-1, UNC-8, MEC-10 and MEC-4) that are co-expressed in mechanosensory neurons and expressed gain-of-function‘d’mutant isoforms inXenopus laevisoocytes. We found that only DEGT-1d, UNC-8d, and MEC-4d formed homomeric channels and that, unlike MEC-4d and UNC-8d, DEGT-1d channels were insensitive to amiloride and its analogs. As reported for rat ASIC1a, NSAIDs inhibit DEGT-1d and UNC-8d channels. Unexpectedly, MEC-4d was strongly potentiated by NSAIDs, an effect that was decreased by mutations in the putative NSAID binding site in the extracellular domain. Collectively, these findings reveal that not all DEG/ENaC/ASIC channels are amiloride-sensitive and that NSAIDs can both inhibit and potentiate these channels.SummaryAnimal physiology depends on degenerin, epithelial sodium, and acid-sensing ion channels (DEG/ENaC/ASICs). By measuring the sensitivity of threeC. elegansDEG/ENaC/ASICs to five amiloride analogs and five NSAIDs, we show that individual channels have distinct pharmacological footprints.
Corporate social responsibility, product innovation, and product line
Authors: Xu Heng 
Published: February 2020

Purpose
This paper aims to investigate a firm’s incentive to innovate its basic product to be socially responsible and its decision on the product line. By constructing a competition model, the paper examines the factors that affect the firm’s choice on its product line with the socially responsible innovation in the presence of altruistic consumers. Such factors include the proportion of the altruistic consumers, the firm’s coordination cost with the basic and innovative products, as well as the consumer’s transportation cost.

Design/methodology/approach
In a model of differentiated products with the competition, the author assumes that a portion of consumers has a strong preference for the socially responsible product (e.g. altruistic consumers). A firm is able to attract altruistic consumers with a socially responsible innovation but it may incur a coordination cost when both the basic and the innovated products are manufactured and sold. In a framework of a sequential game, the firms make a decision on the prices, innovation inputs, as well as the choice on its product line to achieve the expected profit maximization.

Findings
The firm has the incentive to engage in socially responsible innovation to better compete with its rivals. More importantly, the results of the paper explain why some firms wish to manufacture and sell the basic product even though the innovation is successful. The main factors that affect such a firm’s decision include the proportion of the altruistic consumers, the aggregate benefit to all the consumers who purchase the innovative product, the firm’s potential coordination cost and the consumer’s transportation cost.

Originality/value
The paper sheds light on a firm’s corporate social responsibility innovation and its product line determination. The results of this paper can be widely applied in the firm’s strategy of engaging in corporate social responsibility with eco-friendly elements that can attract altruistic consumers in the market. In addition, the findings of the paper can also contribute to policy formulation in terms of innovation. Such a result enables the policymakers to understand the factors that affect the firm’s motivation on innovation and helps them to better guide the firms efficiently participate in the research and development activities.
Hepatitis A virus and hepatitis E virus prevalence relates to human immunodeficiency virus infection in Japanese male blood donors
Authors: Shinohara Naoya , Owada Takashi , Tanaka Ami , Matsubayashi Keiji , Nagai Tadashi , Satake Masahiro 
Published: February 2020

AbstractHepatitis A virus (HAV) has begun to spread globally among men who have sex with men (MSM). Hepatitis E virus (HEV) also may be transmitted through sexual contact among MSM. To assess the current status of these viruses among MSM in Japan, the seroprevalence of both viruses using 503 plasma samples collected between 2009 and 2018 from human immunodeficiency virus (HIV)‐positive male donors who were presumed to be mainly MSM was investigated. Our results suggested that HAV may be spreading within this population, as reported elsewhere. By contrast, the spread of HEV was confirmed only among younger HIV‐positive donors.
Establishment of recombineering genome editing system in Paraburkholderia megapolitana empowers activation of silent biosynthetic gene clusters
Authors: Zheng Wentao , Wang Xue , Zhou Haibo , Zhang Youming , Li Aiying , Bian Xiaoying 
Published: February 2020

SummaryThe Burkholderiales are an emerging source of bioactive natural products. Their genomes contain a large number of cryptic biosynthetic gene clusters (BGCs), indicating great potential for novel structures. However, the lack of genetic tools for the most of Burkholderiales strains restricts the mining of these cryptic BGCs. We previously discovered novel phage recombinases Redαβ7029 from Burkholderiales strain DSM 7029 that could help in efficiently editing several Burkholderiales genomes and established the recombineering genome editing system in Burkholderialse species. Herein, we report the application of this phage recombinase system in another species Paraburkholderia megapolitana DSM 23488, resulting in activation of two silent non‐ribosomal peptide synthetase/polyketide synthase BGCs. A novel class of lipopeptide, haereomegapolitanin, was identified through spectroscopic characterization. Haereomegapolitanin A represents an unusual threonine‐tagged lipopeptide which is longer than the predicted NRPS assembly line. This recombineering‐mediated genome editing system shows great potential for genetic manipulation of more Burkholderiales species to activate silent BGCs for bioactive metabolites discovery.
Characteristics of Uranium Mineralization in Red Clastic Formations in the Southwestern Margin of the Ordos Basin
Authors: ZHANG Zilong , HE Feng , YI Longsheng , FAN Honghai , CAI Yuqi , LIU Hongxu , LIU Xinyang , CHEN Hongbin , JIA Cui , YANG Mengjia 
Published: February 2020

AbstractIn the southwestern margin of the Ordos Basin, uranium mineralization is primarily hosted by predominantly oxidative red clastic formations in the Lower Cretaceous. The main target layers for uranium exploration are the Madongshan and Liwaxia formations of the Liupanshan Group, followed by the Jingchuan Formation of the Zhidan Group. The host rocks (medium‐fine feldspar quartz sandstone), which are bleached to a light grayish white color, contain a minor organic matter component and pyrite. Uranium mineralization changes from surficial infiltration or phreatic oxidation in the upper part to interlayer oxidation in the lower part. Uranium ore bodies are mostly lenticular or tabular in shape, locally shaped like crescent rolls. Individual ore bodies are typically small and shallow. Uranium predominantly manifests as pitchblende and coffinite. Coffinite is usually short and columnar or granular in habit, whereas pitchblende occurs as an irregular colloidal covering on the surface or in fissures of ferric oxide, silicate, clay or carbonate. Secondary uranium minerals are torbernite, uranophane, and uranopilite. Minerals associated with uranium are mainly pyrite, chalcopyrite and, to a minor extent, arsenopyrite and fluorite. The associated elements are Mo, V, Se, Co, Ni, and Mn, the host sandstone being high in Cu and Ba. Overall, the red clastic formations in the southwestern margin of the Ordos Basin are characterized by ‘five multiples but one low’ which means multiple target layers, multiple stages of mineralization, multiple ore body shapes, multiple kinds of uranium minerals, multiple associated elements, but low organic matter. This implies an overall complex uranium metallogenic environment and mineralization process. It is recommended that future uranium exploration should take into consideration regional metallogenic conditions and mineralization features, with target layers in the wide‐smooth synclinal slope being focused on. Most uranium deposits are small to medium in size, and the main type of uranium mineralization can vary by target layer.
Geochemistry and Zircon U‐Pb Geochronology of Early Paleozoic S‐type Granites in the Eastern Qilian Block, Northwest China
Authors: LIU Xiuting , LI Binkai , HAN Jilong , REN Erfeng , GAO Donglin , DU Yongsheng , REN Qianhui , ZHANG Yan 
Published: February 2020

AbstractThe Qilian Block (QB) is a Precambrian micro‐continent located in the northeastern Qinghai–Tibet Plateau. Prevalent Lower Paleozoic granitic magmatic rocks crop out in the QB. A new integrated study of zircon U‐Pb ages and systematic whole‐rock geochemical data for the Xindian, Dongjiazhuang and Xiaogaoling granites in the eastern segment of the QB constrains their emplacement ages, petrogenesis, and regional evolutionary history. U‐Pb dating reveals that the Xindian granite was emplaced 454 Ma, and both the Dongjiazhuang and Xiaogaoling granites were emplaced ca. 440 Ma. Geochemical study shows that all granites belong to the high‐K calc‐alkaline to shoshonitic series and are S‐type granites formed by partial melting of continental crust, mainly metagraywacke. We infer that these ca. 454–445 Ma granites formed in a syn‐collisional setting during the continental collisional between the Qaidam and Qilian blocks.
Use of medicines associated with dry mouth and dental visits in an Australian cohort
Authors: Moffat AK , Apajee J , Pratt NL , Blacker N , Le Blanc VT , Roughead EE 
Published: February 2020

AbstractBackgroundPoor recognition of medicine‐induced dry mouth can have a number of adverse effects, including difficulties with speech, chewing and swallowing dry foods, gum disease, dental caries and oral candidosis. This study examined the prevalence of use of medicines that cause dry mouth and claims for dental services funded by the Department of Veterans’ Affairs (DVA) in an Australian cohort.MethodsWe used the DVA administrative health claims data to identify persons using medicines that can cause dry mouth at 1st of September 2016 and determine their DVA dental claims in the subsequent year. Results were stratified by gender, residence in community or residential aged cared facility and number of medicines.ResultsWe identified 50 679 persons using medicines known to cause dry mouth. Of these, 72.6% were taking only one medicine that may cause dry mouth, and 21.6% were taking two. Less than half (46.2%) of all people taking at least one of these medicines had a dental claim in the following year. A smaller proportion of women (35.9%) made claims than men (56.9%), χ2 = 2248.77, P < 0.0001.ConclusionsTargeted interventions raising awareness of the relationship between some medicines and dry mouth, and the importance of dental visits are warranted.
Assembling “Effective Archaeologies” toward Equitable Futures
Authors: Stahl Ann Brower 
Published: February 2020

ABSTRACTAn urgency compels us to engage how archaeology relates to contemporary situations and future dilemmas as citizens anxiously contemplate their futures. We see “crowd‐sourced” efforts to define pressing questions. A welter of theoretical approaches promises new insight into our relationally configured worlds. We couple awareness of the situated character of knowledge with a commitment to its empirical grounding. In light of this contemporary frame, I explore principles of an “effective archaeology” that imagines its “impacts” beyond narrow “uses.” By attending to how we make facts, archives, and narratives; by placing Western knowledge in productive dialogue with knowledge grounded in other epistemologies; and by embracing a disciplinary responsibility to expand and enlarge imaginings of futures through evidentially robust and critically engaged practice, effective archaeologies hold promise to build toward more equitable futures. [archaeology, epistemology, ontology, knowledge production, collaboration]