bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic antisense therapeutics inhibitingDUX4expression improves muscle function in an FSHD mouse model
Authors: Lu-Nguyen Ngoc , Malerba Alberto , Dickson George , Popplewell Linda 
Published: January 2021

AbstractAberrant expression of the double homeobox 4 (DUX4) gene in skeletal muscle causes muscle deterioration and weakness in Facioscapulohumeral Muscular Dystrophy (FSHD). Since the presence of a permissive pLAM1 polyadenylation signal is essential for stabilization ofDUX4mRNA and translation of DUX4 protein, disrupting the function of this structure can prevent expression of DUX4. We and others have shown promising results using antisense approaches to reduceDUX4expressionin vitroandin vivofollowing local intramuscular administration. Our group has developed further the antisense chemistries, and demonstrate here enhancedin vitroantisense efficacy. The optimal chemistry was conjugated to a cell-penetrating moiety, and for the first time in FSHD research has been systemically administered into a double-transgenic mouse model of FSHD. After four weekly treatments, mRNA quantities ofDUX4and target genes were reduced by 50% that led to a 5% increase in muscle mass, a 52% improvement inin situmuscle strength, and reduction of muscle fibrosis by 17%. Systemic DUX4 inhibition also improved the locomotor activity significantly and reduced the fatigue level by 22%. Our data overall demonstrate that the optimized antisense approach can contribute to future development of a therapeutic strategy for FSHD.
Environment-Dependent Switch between Two Immune Systems againstRalstonia solanacearumInfections in Pepper
Authors: Yang Sheng , Cai Weiwei , Shen Lei , Wu Ruijie , Cao Jianshen , Cai Jinsen , He Shicong , Zheng Yutong , Zhang Qixiong , Wang Aiwen , Guan Deyi , He Shuilin 
Published: January 2021

AbstractAlthough plant diseases generally cause more severe symptoms under conditions of high temperature and high humidity(HTHH), how plant respond to pathogen attack under this condition remains elusive.As an example, we herein comparatively studied pepper(Capsicum annuum) immunity againstRalstonia solanacearumunder HTHH and ambient temperature by approaches of reverse genetics. We found that pepper respond toR.solanacearuminfection by activating salicylic-acid- and jasmonic-acid-mediated immunity at ambient temperature. Under HTHH, However, it no longer activates JA-mediated immunity and activates only transient SA signaling at the early stage ofR.solanacearuminfection, but instead induces cytokinin mediated immunity.These two immune systems are positively regulated by CaWRKY40 via binding the WT-box and a novel W-box like (WL) box, respectively, in an environment-dependent manner:CaWRKY40is activated uponR. solanacearuminfection under HTHH, thereby upregulating ISOPENTENYLTRANSFERASE5(IPT5). The resulting cytokinin then works synergistically with CaWRKY40 in activating a subset of glutathione S-transferase genes via chromatin activation and WL-box binding, but prevent CaWRKY40 from activating ISOCHORISMATE SYNTHASE1 (ICS1) or SA-/JA-dependent pathogenesis-related genes by chromatin inactivation or by blocking WT-box binding.These results highlight the specific pepper immune response toR. solanacearuminfection under HTHH and its synergistic activation byCaWRKY40 and cytokinins.
Transient mitochondria dysfunction confers fungal cross-resistance between macrophages and fluconazole
Authors: Siscar-Lewin Sofía , Gabaldón Toni , Aldejohann Alexander M. , Kurzai Oliver , Hube Bernhard , Brunke Sascha 
Published: January 2021

ABSTRACTLoss or inactivation of antivirulence genes is an adaptive strategy in pathogen evolution.Candida glabratais an important opportunistic pathogen related to baker’s yeast, with the ability to both, quickly increase its intrinsic high level of azole resistance and persist within phagocytes. DuringC. glabrata’s evolution as a pathogen, the mitochondrial DNA polymerase, CgMip1, has been under positive selection. We show thatCgMIP1deletion not only triggers loss of mitochondrial function and apetitephenotype, but increasesC. glabrata’s azole and ER stress resistance, and importantly, its survival in phagocytes. The same phenotype is induced by fluconazole and by exposure to macrophages, conferring a cross-resistance between antifungals and immune cells, and can be found in clinical isolates despite its slow growth. This suggests thatpetiteconstitutes a bet-hedging strategy ofC. glabrata, and potentially a relevant cause of azole resistance. Mitochondrial function may therefore be considered a potential antivirulence factor.
Local ecological knowledge, catch characteristics and evidence of elasmobranch depletions in Western Ghana
Authors: Seidu Issah , Brobbey Lawrence K. , Danquah Emmanuel , Oppong Samuel K. , van Beuningen David , Dulvy Nicholas K. 
Published: January 2021

AbstractLocal Ecological Knowledge has the potential to improve fishery management by providing new data on the fishing efforts, behavior, and abundance trends of fish and other aquatic animals. Here, we relied on local knowledge of fishers to investigate ecological factors that affect elasmobranch fishers‟ operations and the changes in stock status of sharks and rays from 1980 to 2020 in five coastal communities in Ghana. Data were gathered from fishers using participant observation, interviews, focus group discussions, and participatory rural appraisal techniques. The results revealed fisher‟s understanding of six main ecological variables, which are mostly applied to enhance their fishing operations: season and weather conditions, lunar phase, bait type, presence of seabirds and fish movement, color of seawater, and sea current. These ecological features have been applied over the years to enhance fishing operations as well as maximize fisher catch. Fishers reported a profound decline in shark and ray catch from 1980 to 2020 and attributed the decline in size, number, and composition of their catch to overfishing and Illegal, Unreported and Unregulated (IUU) fishing operations. In general, most shark and ray species were abundant in 1980 but have been severely depleted as of 2020, with the exception of Blue Shark (Prionace glauca)and Devil rays (Mobulaspp), which were reported to be common by the interviewed fishers. The first species depleted were the Thresher sharks (Alopiidae), Tiger Shark (Galeocerdo cuvier), Blackchin Guitarfish (Glaucostegus cemiculus), and Lemon Shark (Negaprion brevirostris), which were depleted early in the 2000s. The next depletions of Hammerhead sharks (Sphyrnidae), Bull Shark (Carcharhinus leucas), Sand Tiger Shark (Carcharias taurus), Stingrays (Fontitrygonspp), and Spineback Guitarfish (Rhinobatos irvinei) occurred in the 2010s. We found Local Ecological Knowledge of fishers to be surprisingly consistent with scholarly knowledge and call for their inclusion in research, decision-making and management interventions by biologists and policy makers.
De novo assembly, annotation, and comparative analysis of 26 diverse maize genomes
Authors: Hufford Matthew B. , Seetharam Arun S. , Woodhouse Margaret R. , Chougule Kapeel M. , Ou Shujun , Liu Jianing , Ricci William A. , Guo Tingting , Olson Andrew , Qiu Yinjie , Coletta Rafael Della , Tittes Silas , Hudson Asher I. , Marand Alexandre P. , Wei Sharon , Lu Zhenyuan , Wang Bo , Tello-Ruiz Marcela K. , Piri Rebecca D. , Wang Na , Kim Dong won , Zeng Yibing , O’Connor Christine H. , Li Xianran , Gilbert Amanda M. , Baggs Erin , Krasileva Ksenia V. , Portwood John L. , Cannon Ethalinda K.S. , Andorf Carson M. , Manchanda Nancy , Snodgrass Samantha J. , Hufnagel David E. , Jiang Qiuhan , Pedersen Sarah , Syring Michael L. , Kudrna David A. , Llaca Victor , Fengler Kevin , Schmitz Robert J. , Ross-Ibarra Jeffrey , Yu Jianming , Gent Jonathan I. , Hirsch Candice N. , Ware Doreen , Dawe R. Kelly 
Published: January 2021

AbstractWe report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The data indicate that the number of pan-genes exceeds 103,000 and that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres further reveal the locations and internal structures of major cytological landmarks. We show that combining structural variation with SNPs can improve the power of quantitative mapping studies. Finally, we document variation at the level of DNA methylation, and demonstrate that unmethylated regions are enriched for cis-regulatory elements that overlap QTL and contribute to changes in gene expression.One sentence summaryA multi-genome analysis of maize reveals previously unknown variation in gene content, genome structure, and methylation.
Evolution of cytokine production capacity in ancient and modern European populations
Authors: Domínguez-Andrés Jorge , Kuijpers Yunus , Bakker Olivier B. , Jaeger Martin , Xu Cheng-Jian , van der Meer Jos W.M. , Jakobsson Mattias , Bertranpetit Jaume , Joosten Leo A.B. , Li Yang , Netea Mihai G. 
Published: January 2021

AbstractAs our ancestors migrated throughout the different continents, natural selection increased the presence of alleles advantageous in the new environments. Heritable variations that alter the susceptibility to diseases vary with the historical period, the virulence of the infections, and their geographical spread. In this study we built polygenic scores for heritable traits influencing the genetic adaptation in the production of cytokines and immune-mediated disorders, including infectious, inflammatory, and autoimmune diseases, and applied them to the genomes of several ancient European populations. We observed that the advent of the Neolithic was a turning point for immune-mediated traits in Europeans, favoring those alleles linked with the development of tolerance against intracellular pathogens and promoting inflammatory responses against extracellular microbes. These evolutionary patterns are also associated with an increased presence of traits related to inflammatory and auto-immune diseases.
Microclimates can be accurately predicted across ecologically important remote ecosystems
Authors: Baker D.J. , Dickson C.R. , Bergstrom D.M. , Whinam J. , Maclean I.M.D , McGeoch M.A. 
Published: January 2021

ABSTRACTMicroclimate information is often crucial for understanding ecological patterns and processes, including under climate change, but is typically absent from ecological and biogeographic studies owing to difficulties in obtaining microclimate data. Recent advances in microclimate modelling, however, suggest that microclimate conditions can now be predicted anywhere at any time using hybrid physically- and empirically-based models. Here, for the first time, we test the utility of this approach across a remote, inaccessible, and climate change threatened polar island ecosystem at ecologically relevant scales. Microclimate predictions were generated at a 100 × 100 m grain (at a height of 4 cm) across the island, with models parameterised using either meteorological observations from the island’s weather station (AWS) or climate reanalysis data (CRA). AWS models had low error rates and were highly correlated with observed seasonal and daily temperatures (root mean squared error of predicted seasonal average Tmean≤ 0.6 °C; Pearson’s correlation coefficient (r) for the daily Tmean≥ 0.86). By comparison, CRA models had a slight warm bias in all seasons and a smaller diurnal range in the late summer period thanin situobservations. Despite these differences, the modelled relationship between the percentage cover of the threatened endemic cushion plantAzorella macquariensisand microclimate varied little with the source of microclimate data (r = 0.97), suggesting that both model parameterisations capture similar patterns of spatial variation in microclimate conditions across the island ecosystem. Here, we have shown that the accurate prediction of microclimate conditions at ecologically relevant spatial and temporal scales is now possible using hybrid physically- and empirically-based models across even the most remote and climatically extreme environments. These advances will help add the microclimate dimension to ecological and biogeographic studies, which could be critical for delivering climate change-resilient conservation planning in climate-change exposed ecosystems.
Discovery and functional assessment of a novel adipocyte population driven by intracellular Wnt/β-catenin signaling in mammals
Authors: Liu Zhi , Chen Tian , Zhang Sicheng , Yang Tianfang , Gong Yun , Deng Hong-Wen , Bai Ding , Tian Weidong , Chen YiPing 
Published: January 2021

ABSTRACTWnt/β-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of adipocytes that exhibit persistent activity of Wnt/β-catenin signaling, as revealed by theTcf/Lef-Gfpreporter allele, in embryonic and adult mouse fat depots, named as Wnt+adipocytes. We showed that the β-catenin-mediated signaling activation in these cells is Wnt ligand- and receptor-independent but relies on AKT/mTOR pathway and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Genetic lineage-tracing and targeted cell ablation studies revealed that these adipocytes convert into beige adipocytes directly and are also required for beige fat recruitment under thermal challenge, demonstrating both cell autonomous and non-cell autonomous roles in adaptive thermogenesis. Furthermore, mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging in adipose tissues and systemic glucose homeostasis.
Using Bayesian Optimization to Identify Optimal Exoskeleton Parameters Targeting Propulsion Mechanics: A Simulation Study
Authors: Kim GilHwan , Sergi Fabrizio 
Published: January 2021

AbstractIn this study, we determined the feasibility of modeling the relationship between robot control parameters and propulsion mechanics as a Gaussian process. Specifically, we used data obtained in a previous experiment that used pulses of torque applied at the hip and knee joint, at early and late stance, to establish the relationship a 3D control parameter space and the resulting changes in hip extension and propulsive impulse. We estimated Gaussian models both at the group level and for each subject. Moreover, we used the estimated subject-specific models to simulate virtual human-in-the-loop optimization (HIL) experiments based on Bayesian optimization to establish their convergence under multiple combinations of acquisition functions and seed point selection methods.Results of the group-level model are in agreement with those obtained with linear mixed effect model, thus establishing the feasibility of Gaussian process modeling. The estimated subject-specific optimal conditions have large between-subject variability in the metric of propulsive impulse, with only 31% of subjects featuring a subject-specific optimal point in the surrounding of the group-level optimal point. Virtual HIL experiments indicate that expected improvement is the most effective acquisition method, while no significant effect of seed point selection method was observed. Our study may have practical effects on the adoption of HIL robot-assisted training methods focused on propulsion.
Myoglobin primary structure reveals multiple convergent transitions to semi-aquatic life in the world’s smallest mammalian divers
Authors: He Kai , Eastman Triston G. , Czolacz Hannah , Li Shuhao , Shinohara Akio , Kawada Shin-ichiro , Springer Mark S. , Berenbrink Michael , Campbell Kevin L. 
Published: January 2021

AbstractIdentifying the phylogenomic underpinnings of specialized phenotypes that fueled transitions into new adaptive zones is central to evolutionary biology but is often confounded by a fragmentary fossil record, morphological convergence, and unresolved phylogenetic relationships. The speciose mammalian order Eulipotyphla (e.g., moles, shrews, hedgehogs, solenodons) combines an unusual diversity of semi-aquatic, semi-fossorial, and fossorial forms that arose from terrestrial forbearers, yet the ecomorphological pathways leading to these lifestyles have been disputed for a century and more, calling for novel approaches. Here we resolve previously intractable eulipotyphlan intra-family relationships and establish the net surface charge of the oxygen-storing muscle protein myoglobin-readily determined from its primary structure-as a molecular signature to trace ancient lifestyle transitions based on protein sequence alone. Our analyses confidently resolve fossorial habits having evolved twice in talpid moles and reveal five independent origins of a semi-aquatic lifestyle in the order housing the world’s smallest endothermic divers.
Identifying Plasmodium falciparum transmission patterns through parasite prevalence and entomological inoculation rate
Authors: Amoah Benjamin , McCann Robert S. , Kabaghe Alinune N. , Mburu Monicah , Chipeta Michael G. , Moraga Paula , Gowelo Steven , Tizifa Tinashe , van den Berg Henk , Mzilahowa Themba , Takken Willem , van Vugt Michéle , Phiri Kamija S. , Diggle Peter J. , Terlouw Dianne J. , Giorgi Emanuele 
Published: January 2021

AbstractMonitoring malaria transmission is a critical component of efforts to achieve targets for elimination and eradication. Two commonly monitored metrics of transmission intensity are parasite prevalence (PR) and the entomological inoculation rate (EIR). Using geostatistical methods, we investigate the relationship betweenPlasmodium falciparumPR and EIR using data collected over 38 months in a rural area of Malawi. Our results indicate that hotspots identified through the EIR and PR partly overlapped during high transmission seasons but not during low transmission seasons. The estimated relationship showed a one-month delayed effect of EIR on PR such that at low transmission levels increases in EIR are associated with rapid rise in PR, but at high transmission levels, decreases in EIR do not translate into notable reductions in PR. Our study emphasises the need for integrated malaria control strategies that combines vector and human host managements monitored by both entomological and parasitaemia indices.
Frequency preference response in covalent modification cycles under substrate sequestration conditions
Authors: Szemere Juliana Reves , Rotstein Horacio G , Ventura Alejandra C 
Published: January 2021

AbstractCovalent modification cycles (CMCs) are basic units of signaling systems and their properties are well understood. However, the behavior of such systems has been mostly characterized in situations where the substrate is in excess over the modifying enzymes. Experimental data on protein abundance suggest that the enzymes and their target proteins are present in comparable concentrations, leading to a different scenario in which the substrate is mostly sequestered by the enzymes. In this enzyme-in-excess regime, CMCs have been shown to exhibit signal termination, the ability of the product to return to a stationary value lower than the its peak in response to constant stimulation, while this stimulation is still active, with possible implications for the ability of systems to adapt to environmental inputs. We characterize the conditions leading to signal termination in CMCs in the enzyme-in-excess regime. We also demonstrate that this behavior leads to a preferred frequency response (band-pass filters) when the cycle is subjected to periodic stimulation, while the literature reports that CMCs investigated so far behave as low pass filters. We characterize the relationship between signal termination and the preferred frequency response to periodic inputs and we explore the dynamic mechanism underlying these phenomena. Finally, we describe how the behavior of CMCs is reflected in similar types of responses in the cascades of which they are part. Evidence of protein abundancein vivoshows that enzymes and substrates are present in comparable concentrations, thus suggesting that signal termination and frequency preference response to periodic inputs are also important dynamic features of cell signaling systems, which have been overlooked.
Multiplatform Integrative Analyses of Immunosuppressive Signatures in Cortisol-secreting Adrenocortical Carcinoma
Authors: Baechle Jordan J. , Hanna David N. , Konjeti Sekhar R. , Rathmell Jeffrey C. , Rathmell W. Kimryn , Baregamian Naira 
Published: January 2021

AbstractAdrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy and nearly half of ACC tumors have been shown to overproduce and secrete adrenal steroids. Excess cortisol secretion, in particular, has been associated with poor prognosis among ACC patients. Furthermore, recent immunotherapy clinical trials demonstrated significant immunoresistance among cortisol-secreting ACC (CS-ACC) patients when compared to their non-Cortisol-secreting (nonCS-ACC) counterparts. The immunosuppressive role of excess glucocorticoid therapies and secretion is well established, however, the impact of the cortisol hypersecretion on ACC tumor microenvironment (TME), immune expression profiles, and immune cell responses remain largely undefined. In this study, we characterized the TME of ACC patients and compared the immunogenomic profiles of nonCS-ACC and CS-ACC tumors to assess the impact of differentially expressed genes (DEGs) related to immune processes on patient prognosis. Comprehensive multiplatform immunogenomic computational analyses of ACC tumors deciphered an immunosuppressive expression profile with a direct impact on patient survival. We identified several primary immunogenomic prognostic indicators and potential targets within the tumor immune landscape of CS-ACC that define a distinct TME and provide additional insight into the understanding of potential contributory mechanisms underlying failure of initial immunotherapeutic trials and poor prognosis of patients with CS-ACC.