bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality from COVID in Colombia and Peru: Analyses of Mortality Data and Statistical Forecasts
Authors: Brown Patrick E , Greenwald Zoë R , Salinas Luis Ernesto , Martens Gabriel Aguirre , Newcombe Leslie , Rodriguez Peter S , Gelband Hellen , Veillard Jeremy , Jha Prabhat 
Published: August 2020

AbstractNational predictions of the course of COVID mortality can be used to plan for effective healthcare responses as well as to support COVID policymaking. We developed the Global COVID Assessment of Mortality (GCAM), a statistical model with continually improving precision that combines actual mortality counts with Bayesian inference, to predict COVID trends, currently until December 1, 2020. In Colombia, the GCAM analysis found the peak of COVID mortality around August 12 and an expected total of COVID deaths of 24,000-31,000, or 48%-92% over the total through August 21. In Peru, a first mortality peak occurred around May 24, and given the current trajectory, a second peak is predicted around September 6. Peru can expect 29,000-43,000 COVID deaths, representing an increase of 7%-55% over COVID deaths through August 21. GCAM projections are also used to estimate medical surge capacity needs. To gauge the reliability of COVID mortality forecasts, we compared all-cause mortality from January through June 2020 with average all-cause mortality in previous years in Colombia and Peru, and found that the excesses were consistent with GCAM forecast, most notably a doubling of overall mortality from May 25-June 7th of weeks in Peru. The GCAM results predict that as a percentage of all adult deaths in previous years, Colombia can expect about 13% excess from COVID deaths, whereas Peru can expect 34% excess. Comparisons of GCAM analyses of several other countries with Colombia and Peru demonstrate the extreme variability that characterizes COVID mortality around the world, emphasizing the need for country-specific analyses and ongoing monitoring as more mortality data become available.
Orthosteric-allosteric dual inhibitors of PfHT1 as selective anti-malarial agents
Authors: Huang Jian , Yuan Yafei , Zhao Na , Pu Debing , Tang Qingxuan , Zhang Shuo , Luo Shuchen , Yang Xikang , Wang Nan , Xiao Yu , Zhang Tuan , Liu Zhuoyi , Sakata-Kato Tomoyo , Jiang Xin , Kato Nobutaka , Yan Nieng , Yin Hang 
Published: August 2020

AbstractArtemisinin-resistant malaria parasites have emerged and been spreading, posing a significant public health challenge. Anti-malarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a “selective starvation” strategy by selectively inhibitingPlasmodium falciparumhexose transporter 1 (PfHT1), the sole hexose transporter inPlasmodium falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. Comparison of the crystal structures of human GLUT3 and PfHT1 bound to C3361, a PfHT1-specific moderate inhibitor, revealed an inhibitor binding-induced pocket that presented a promising druggable site. We thereby designed small-molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure-activity relationship (SAR) studies, the TH-PF series was identified to selectively inhibit PfHT1 over GLUT1 and potent against multiple strains of the blood-stageP. falciparum. Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously targeting the orthosteric and allosteric sites of a transporter.Significance statementBlocking sugar uptake inP. falciparumby selectively inhibiting the hexose transporter PfHT1 kills the blood-stage parasites without affecting the host cells, indicating PfHT1 as a promising therapeutic target. Here, we report the development of novel small-molecule inhibitors that are selectively potent to the malaria parasites over human cell lines by simultaneously targeting the orthosteric and the allosteric binding sites of PfHT1. Our findings established the basis for the rational design of next-generation anti-malarial drugs.
MiMIC analysis reveals an isoform specific role forDrosophilaMusashi in follicle stem cell maintenance and escort cell function
Authors: Siddall Nicole A. , Casagranda Franca , Johanson Timothy M. , Dominado Nicole , Heaney James , Sutherland Jessie M. , McLaughlin Eileen A. , Hime Gary R. 
Published: August 2020

AbstractTheDrosophilaovary is regenerated from germline and somatic stem cell populations that have provided fundamental conceptual understanding on how adult stem cells are regulated within their niches. Recent ovarian transcriptomic studies have failed to identify mRNAs that are specific to follicle stem cells (FSCs), suggesting that their fate may be regulated post-transcriptionally. We have identified that the RNA-binding protein, Musashi (Msi) is required for maintaining the stem cell state of FSCs. Loss ofmsifunction results in stem cell loss, not due to cell death, but mutant FSCs upregulate Lamin C, indicating a change in differentiation state. Inmsimutant ovaries, Lamin C upregulation was also observed in posterior escort cells and mutant somatic cells within regions 2/3 were dysfunctional, as evidenced by the presence of germline cyst collisions and fused egg chambers. Themsilocus produces two classes of mRNAs (long and short). We show that FSC maintenance and escort cell function specifically requires the long transcripts, thus providing the first evidence of isoform-specific regulation in a population ofDrosophilaepithelial cells. We further demonstrate that although male germline stem cells have previously been shown to require Msi function to prevent differentiation this is not the case for female germline stem cells, indicating that these similar stem cell types have different requirements for Msi, in addition to the differential use of Msi isoforms between soma and germline.
Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria
Authors: Hall Thomas J. , Mullen Michael P. , McHugo Gillian P. , Killick Kate E. , Ring Siobhán C. , Berry Donagh P. , Correia Carolina N. , Browne John A. , Gordon Stephen V. , MacHugh David E. 
Published: August 2020

AbstractBovine tuberculosis (bTB), caused by infection withMycobacterium bovis, is a major disease affecting cattle globally as well as being a zoonotic risk to human health. The key innate immune cell that first encountersM. bovisis the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use multi-omics and network biology approaches to analyse the macrophage transcriptional response toM. bovisinfection and identify core infection response pathways and gene modules. These outputs were integrated with results from genome-wide associations ofM. bovisinfection to enhance the detection of putative genomic variants for disease resistance. Our results show that network-based integration of relevant transcriptomics data can extract additional information from large genome-wide associations and that this approach could also be used to integrate relevant functional genomics outputs with results from genomic association studies for human tuberculosis caused by the relatedMycobacterium tuberculosis.
Evaluation of the 7 & 7 Synch and 7-day CO-Synch + CIDR®protocols for estrus synchronization of beef cows prior to fixed-time artificial insemination with conventional or sex-sorted semen
Authors: Andersen C.M. , Bonacker R.C. , Smith E.G. , Spinka C.M. , Poock S.E. , Thomas J.M. 
Published: August 2020

AbstractAn experiment was designed to compare the recently developed 7 & 7 Synch and the 7-day CO-Synch + CIDR protocols for synchronization of estrus among beef cows prior to fixed-time artificial insemination (FTAI) with conventional or sex-sorted semen.Bos tauruscows (n = 1538) were blocked based on age and days postpartum (DPP) and randomly assigned to protocol and semen type. Cows treated with the 7-day CO-Synch + CIDR protocol (n = 769) received administration of gonadotropin-releasing hormone (GnRH; 100 μg gonadorelin) and insertion of a 1.38 g intravaginal progesterone releasing insert (CIDR) on Day -10, and administration of prostaglandin F2α(PG; 500 μg cloprostenol) coincident with CIDR removal on Day -3. Cows treated with 7 & 7 Synch (n = 769) received PG and insertion of CIDR on Day -17, GnRH on Day -10, and PG coincident with CIDR removal on Day -3. Estrus detection aids (Estrotect™) were applied to all cows on Day -3, and activation status was recorded at FTAI. Cows received FTAI 66 h after CIDR removal with either conventional (20 × 106cells per unit) or sex-sorted (4 × 106cells per unit; SexedULTRA 4M™) semen. A greater proportion of cows expressed estrus (P= 0.01) prior to FTAI following 7 & 7 Synch (82%; 629/769) compared with the 7-day CO-Synch + CIDR (64%; 492/769). Estrus expression was also affected by protocol × DPP (P= 0.0004), with 7 & 7 Synch resulting in a greater increase in the proportion of cows expressing estrus prior to FTAI among cows with greater DPP. Across protocols, body condition score (BCS) affected (P= 0.05) estrus expression, with greater proportion of cows expressing estrus prior to FTAI at greater BCS. Sex-sorted semen resulted in reduced (P< 0.0001) pregnancy rates to FTAI. Irrespective of semen type, greater (P= 0.001) pregnancy rates to FTAI were obtained among cows treated with 7 & 7 Synch (conventional semen: 72% [280/389]; sex-sorted semen: 52% [199/380]) compared with the 7-day CO-Synch + CIDR (conventional semen: 60% [231/383]; sex-sorted semen: 44% [171/386]). In summary, 7 & 7 Synch resulted in an increased proportion of cows expressing estrus prior to FTAI and an increased pregnancy rate to FTAI with conventional and sexed semen. With these results and ease of application, 7 & 7 Synch offers potential as a platform to improve success with fixed-time AI in beef cows.
DNA methylation landscapes of matched primary and recurrent high grade serous ovarian cancers are preserved throughout disease progression and chemoresistance
Authors: Gull Nicole , Jones Michelle R. , Peng Pei-Chen , Coetzee Simon G. , Silva Tiago C. , Plummer Jasmine T. , Reyes Alberto Luiz P. , Davis Brian D. , Chen Stephanie , Lawrenson Kate , Lester Jenny , Walsh Christine , Rimel Bobbie J. , Li Andrew J. , Cass Ilana , Berg Yonatan , Govindavari John-Paul B. , Rutgers Joanna K.L. , Karlan Beth Y. , Berman Benjamin P. , Gayther Simon A. 
Published: August 2020

ABSTRACTLittle is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). We performed whole genome bisulfite sequencing (WGBS) and whole transcriptome sequencing (RNA-seq) to establish methylation and gene expression signatures in 62 primary and recurrent tumors from 28 patients diagnosed with stage III/IV HGSOC. Eleven of these patients carried pathogenic germlineBRCA1/BRCA2mutations. Genome-wide methylation and transcriptomic features identified in primary tumors were largely preserved in matched recurrent tumors from the same patient (P-value = 7.16 × 10−7and 1.41 × 10−3inBRCA1/2and non-BRCA1/2cases respectively). Tumors fromBRCA1/2carriers displayed high levels of heterogeneity, with significantly more shared methylation changes identified between primary and recurrent tumors from non-BRCA1/2patients, which may be related to the poorer survival we observe in HGSOCs from non-BRCA1/2carriers (P-value = 0.0056). Partially methylated domains (PMDs) dominated the epigenetic variation across all tumors, and were more hypomethylated inBRCA1/2than non-BRCA1/2cases. Differential gene expression analysis identified upregulation of genes from immune pathways including antigen processing and presentation in tumors fromBRCA1/2carriers, implicating increased immune response in the improved survival observed in these patients. In summary, this study shows a previously unreported conservation of methylation and gene expression in recurrent HGSOCs. These data have implications for the possible effectiveness of epigenetic based therapies to treat both primary and recurrent ovarian cancers.
A unique view of SARS-CoV-2 through the lens of ORF8 protein
Authors: Hassan Sk. Sarif , Ghosh Shinjini , Attrish Diksha , Choudhury Pabitra Pal , Seyran Murat , Pizzol Damiano , Adadi Parise , El-Aziz Tarek Mohamed Abd , Soares Antonio , Kandimalla Ramesh , Lundstrom Kenneth , Tambuwala Murtaza , Aljabali Alaa A. A. , Lal Amos , Azad Gajendra Kumar , Uversky Vladimir N. , Sherchan Samendra P. , Baetas-da-Cruz Wagner , Uhal Bruce D. , Rezaei Nima , Brufsky Adam M. 
Published: August 2020

AbstractImmune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through downregulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geolocations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8.
Integrated Collection of Stem Cell Bank data, a data portal for standardized stem cell information
Authors: Chen Ying , Sakurai Kunie , Maeda Sumihiro , Masui Tohru , Okano Hideyuki , Dewender Johannes , Seltmann Stefanie , Kurtz Andreas , Masuya Hiroshi , Nakamura Yukio , Sheldon Michael , Schneider Juliane , Stacey Glyn N. , Panina Yulia , Fujibuchi Wataru 
Published: August 2020

SUMMARYThe last decade has witnessed an extremely rapid increase in the number of newly established stem cell lines. However, due to the lack of a standardized format, data exchange among stem cell line resources has been challenging, and no system can search all stem cell lines across resources worldwide. To solve this problem, we have developed Integrated Collection of Stem Cell Bank data (ICSCB) (http://icscb.stemcellinformatics.org/), the largest database search portal for stem cell line information, based on the standardized data items and terms of the MIACARM framework. Currently, ICSCB can retrieve >16,000 cell lines from four major data resources in Europe, Japan, and the United States. ICSCB is automatically updated to provide the latest cell line information, and its integrative search helps users collect cell line information for over 1,000 diseases including many rare diseases worldwide, which has been a formidable task, thereby distinguishing itself from other database search portals.
Potential For Applying Continuous Directed Evolution To Plant Enzymes
Authors: García-García Jorge D. , Joshi Jaya , Patterson Jenelle A. , Trujillo-Rodriguez Lidimarie , Reisch Christopher R. , Javanpour Alex A. , Liu Chang C. , Hanson Andrew D. 
Published: August 2020

SUMMARYPlant evolution has produced enzymes that may not be optimal for maximizing yield and quality in today’s agricultural environments and plant biotechnology applications. By improving enzyme performance, it should be possible to alleviate constraints on yield and quality currently imposed by kinetic properties or enzyme instability. Enzymes can be optimized faster than naturally possible by applying directed evolution, which entails mutating a target genein vitroand screening or selecting the mutated gene products for the desired characteristics. Continuous directed evolution is a more efficient and scalable version that accomplishes the mutagenesis and selection steps simultaneouslyin vivovia error-prone replication of the target gene and coupling of the host cell’s growth rate to the target gene’s function. However, published continuous systems require custom plasmid assembly, and convenient multipurpose platforms are not available. We discuss two systems suitable for continuous directed evolution of enzymes, OrthoRep inSaccharomyces cerevisiaeand EvolvR inEscherichia coli, and our pilot efforts to adapt each system for high-throughput plant enzyme engineering. To test our modified systems, we used the thiamin synthesis enzyme THI4, previously identified as a prime candidate for improvement. Our adapted OrthoRep system shows promise for efficient plant enzyme engineering.
Neural tracking of the fundamental frequency of the voice: the effect of voice characteristics
Authors: Van Canneyt Jana , Wouters Jan , Francart Tom 
Published: August 2020

AbstractTraditional electrophysiological methods to study temporal auditory processing of the fundamental frequency of the voice (f0) often use unnaturally repetitive stimuli. In this study, we investigated f0 processing of meaningful continuous speech. EEG responses evoked by stories in quiet were analysed with a novel method based on linear modelling that characterizes the neural tracking of the f0. We studied both the strength and the spatio-temporal properties of the f0-tracking response. Moreover, different samples of continuous speech (six stories by four speakers: two male and two female) were used to investigate the effect of voice characteristics on the f0 response.The results indicated that response strength is inversely related to f0 frequency and rate of f0 change throughout the story. As a result, the male-narrated stories in this study (low and steady f0) evoked stronger f0-tracking compared to female-narrated stories (high and variable f0), for which many responses were not significant. The spatio-temporal analysis revealed that f0-tracking response generators were not fixed in the brainstem but were voice-dependent as well. Voices with high and variable f0 evoked subcortically-dominated responses with a latency between 7 and 12 ms. Voices with low and steady f0 evoked responses that are both subcortically (latency of 13-15 ms) and cortically (latency of 23-26 ms) generated, with the right primary auditory cortex as a likely cortical source. Finally, additional experiments revealed that response strength greatly improves for voices with strong higher harmonics, which is particularly useful to boost the small responses evoked by voices with high f0.
EEG Alpha Power Predicts the Temporal Sensitivity of Multisensory Integration
Authors: London Raquel E. , Benwell Christopher S. Y. , Cecere Roberto , Quak Michel , Thut Gregor , Talsma Durk 
Published: August 2020

AbstractPre-stimulus EEG oscillations, especially in the alpha range (8-13 Hz), can affect the integration of stimulus features into a coherent percept. The effects of alpha power are often explained in terms of alpha’s inhibitory functions, whereas effects of alpha frequency have bolstered theories of discrete perceptual cycles, where the length of a cycle, or window of integration, is determined by alpha frequency. Such studies typically employ visual detection paradigms with near-threshold or even illusory stimuli. It is unclear whether such results generalize to above-threshold stimuli. Here, we recorded electroencephalography, while measuring temporal discrimination sensitivity in a temporal order judgement task using above-threshold auditory and visual stimuli. We tested whether pre-stimulus oscillations predict audio-visual temporal discrimination sensitivity on a trial-by-trial basis. By applying a jackknife procedure to link single-trial pre-stimulus oscillatory power and instantaneous frequency to psychometric measures, we identified two highly overlapping clusters over posterior sites. One where lower alpha power was associated with higher temporal sensitivity of audiovisual discrimination, and another where higher instantaneous alpha-frequency predicted higher temporal discrimination sensitivity. A follow-up analysis revealed that these effects were not independent, and that the effect of instantaneous frequency could be explained by power modulations in the lower alpha band. These results suggest that temporal sensitivity for above-threshold multisensory stimuli changes spontaneously from moment to moment and is likely related to fluctuations in cortical excitability. Moreover, our results caution against interpreting instantaneous frequency effects as independent from power effects if these effects overlap in time and space.
ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons
Authors: Garone Maria Giovanna , Birsa Nicol , Rosito Maria , Salaris Federico , Mochi Michela , de Turris Valeria , Nair Remya R. , Cunningham Thomas J. , Fisher Elizabeth M. C. , Morlando Mariangela , Fratta Pietro , Rosa Alessandro 
Published: August 2020

ABSTRACTMutations in the RNA-binding protein (RBPs) FUS have been genetically associated with the motoneuron disease amyotrophic lateral sclerosis (ALS). Using both human induced pluripotent stem cells and mouse models, we found that FUS-ALS causative mutations affect the activity of two relevant RBPs with important roles in neuronal RNA metabolism: HuD/ELAVL4 and FMRP. Mechanistically, mutant FUS leads to upregulation of HuD protein levels through competition with FMRP forHuDmRNA 3’UTR binding. In turn, increased HuD levels overly stabilize the transcript levels of its targets, NRN1 and GAP43. As a consequence, mutant FUS motoneurons show increased axon branching and growth upon injury, which could be rescued by dampening NRN1 levels. Since similar phenotypes have been previously described in SOD1 and TDP-43 mutant models, increased axonal growth and branching might represent broad early events in the pathogenesis of ALS.
Casino development and regulation in Asia: the experience of Macau and Singapore for Japan and other destinations
Authors: Ho Hong Wai 
Published: August 2020

PurposeThe purpose of this paper is to examine the casino development and regulation in Macau and Singapore. The paper also seeks to assess the potential for casino development in Asia, with a particular focus on the prospects of Japan's casino resorts.Design/methodology/approachThe paper reviews the gaming history, gaming/tourism policies and casino regulations of Macau and Singapore. The key aspects concerned with the casino development in Asia are also examined.FindingsThe paper identifies the fundamentals that have contributed to the prosperity of casino resorts in Macau and Singapore, as well as highlights the potential and challenges for the casino developments in Japan and other Asian destinations.Research limitations/implicationsA number of legal and tourism-related factors are identified to be the determinants of casino development. However, more research is needed to examine the political, economic and socio-cultural factors associated with casino gaming.Practical implicationsThe paper, discussing the casino development and regulation in Macau and Singapore, provides practical implications for the design of gaming/tourism policy and casino control in Japan and other prospective gaming jurisdictions.Originality/valueThe paper contributes to the growing body of literature on the gaming law and casino development in Asia and provides insights for policymakers contemplating the adoption of casinos as a strategic policy for tourism development and economic growth.