bluuebunny/crossref_metadata_2025_split huggingface dataset:
Costa Rica
Authors: Molina Iván 
Published: August 2020

Abstract
From 1840 to the present, Costa Rica has sharedsimilar historical processes with its Central American neighbors, but differed from them by consolidating a stable democracy. The Costa Rican dominant groups never had the resources or sufficient means to subjugate the middle classes or the popular sectors, whose demands for policies that satisfied their interests shaped very early a culture and a state prone to social reform. In the long term, this modernizing trend played in favor of the social and cultural inclusion of the population, the reduction of inequalities, and the legitimacy of the political system.
Post-Executive Activities
Authors: Musella Fortunato 
Published: August 2020

AbstractThis chapter will focus on political careers of executive members after the end of their term in office, with particular reference to political leaders. After reviewing literature on post-executive political career, it will focus on more recent research directions in this field: (a) the attempt to extend the number of empirical observations by assuming systematic and large-N comparative research; (b) the move from an empiricist-individualistic conception of career patterns to an institutional one; (c) the investigation on new politics-market linkages in democratic regimes coming from the new activism of former leaders. Jointly considering these lines, the final part of the chapter will be devoted to delineate some lines of future research agenda on post-executive patterns and raise crucial questions concerning representative regimes.
CO Multi-line Imaging of Nearby Galaxies (COMING). X. Physical conditions of molecular gas and the local SFR–mass relation
Authors: Morokuma-Matsui Kana , Sorai Kazuo , Sato Yuya , Kuno Nario , Takeuchi Tsutomu T , Salak Dragan , Miyamoto Yusuke , Yajima Yoshiyuki , Muraoka Kazuyuki , Kaneko Hiroyuki 
Published: August 2020

Abstract
We investigate the molecular gas properties of galaxies across the main sequence of star-forming (SF) galaxies in the local Universe using 12CO(J = 1–0), hereafter 12CO, and 13CO(J = 1–0), hereafter 13CO, mapping data of 147 nearby galaxies obtained in the COMING project, a legacy project of the Nobeyama Radio Observatory. In order to improve the signal-to-noise ratios of both lines, we stack all the pixels where 12CO emission is detected after aligning the line center expected from the first-moment map of 12CO. As a result, 13CO emission is successfully detected in 80 galaxies with a signal-to-noise ratio larger than three. The error-weighted mean of the integrated-intensity ratio of 12CO to 13CO lines (R1213) of the 80 galaxies is 10.9, with a standard deviation of 7.0. We find that (1) R1213 positively correlates to specific star-formation rate (sSFR) with a correlation coefficient of 0.46, and (2) both the flux ratio of IRAS 60 μm to 100 μm (f60/f100) and the inclination-corrected linewidth of 12CO stacked spectra ($\sigma _{{\rm ^{12}CO},i}$) also correlate with sSFR for galaxies with the R1213 measurement. Our results support the scenario where R1213 variation is mainly caused by changes in molecular gas properties such as temperature and turbulence. The consequent variation of the CO-to-H2 conversion factor across the SF main sequence is not large enough to completely extinguish the known correlations between sSFR and Mmol/Mstar (μmol) or star-formation efficiency (SFE) reported in previous studies, while this variation would strengthen (weaken) the sSFR–SFE (sSFR–μmol) correlation.
Disentangling Sources of Gene Tree Discordance in Phylogenomic Data Sets: Testing Ancient Hybridizations in Amaranthaceae s.l
Authors: Morales-Briones Diego F , Kadereit Gudrun , Tefarikis Delphine T , Moore Michael J , Smith Stephen A , Brockington Samuel F , Timoneda Alfonso , Yim Won C , Cushman John C , Yang Ya 
Published: August 2020

AbstractGene tree discordance in large genomic data sets can be caused by evolutionary processes such as incomplete lineage sorting and hybridization, as well as model violation, and errors in data processing, orthology inference, and gene tree estimation. Species tree methods that identify and accommodate all sources of conflict are not available, but a combination of multiple approaches can help tease apart alternative sources of conflict. Here, using a phylotranscriptomic analysis in combination with reference genomes, we test a hypothesis of ancient hybridization events within the plant family Amaranthaceae s.l. that was previously supported by morphological, ecological, and Sanger-based molecular data. The data set included seven genomes and 88 transcriptomes, 17 generated for this study. We examined gene-tree discordance using coalescent-based species trees and network inference, gene tree discordance analyses, site pattern tests of introgression, topology tests, synteny analyses, and simulations. We found that a combination of processes might have generated the high levels of gene tree discordance in the backbone of Amaranthaceae s.l. Furthermore, we found evidence that three consecutive short internal branches produce anomalous trees contributing to the discordance. Overall, our results suggest that Amaranthaceae s.l. might be a product of an ancient and rapid lineage diversification, and remains, and probably will remain, unresolved. This work highlights the potential problems of identifiability associated with the sources of gene tree discordance including, in particular, phylogenetic network methods. Our results also demonstrate the importance of thoroughly testing for multiple sources of conflict in phylogenomic analyses, especially in the context of ancient, rapid radiations. We provide several recommendations for exploring conflicting signals in such situations. [Amaranthaceae; gene tree discordance; hybridization; incomplete lineage sorting; phylogenomics; species network; species tree; transcriptomics.]
Transcranial Alternating Current Stimulation of the Primary Motor Cortex after Skill Acquisition Improves Motor Memory Retention in Humans: A Double-Blinded Sham-Controlled Study
Authors: Yamaguchi Tomofumi , Svane Christian , Forman Christian Riis , Beck Mikkel Malling , Geertsen Svend Sparre , Lundbye-Jensen Jesper , Nielsen Jens Bo 
Published: August 2020

Abstract
Consolidation leading to retention of motor memory following motor practice involves activity-dependent plastic processes in the corticospinal system. To investigate whether beta-band transcranial alternating current stimulation (tACS) applied immediately following skill acquisition can enhance ongoing consolidation processes and thereby motor skill retention 20 adults participated in a randomized, double-blinded, sham-controlled study. Participants received tACS at peak beta-band corticomuscular coherence (CMC) frequency or sham tACS for 10 min following practice of a visuomotor ankle dorsiflexion task. Performance was measured as the average percentage time on target. Electroencephalograhy (EMG) was measured at Cz and EMG from the right tibialis anterior muscle. CMC and intramuscular coherence (IMC) were estimated during 2-min tonic dorsiflexion. Motor skill retention was tested 1 and 7 days after motor practice. From the end of motor practice to the retention tests, motor performance improved more in the tACS group compared with the sham tACS group after 1 (P = 0.05) and 7 days (P &lt; 0.001). At both retention tests, beta-band IMC increased in the tACS group compared with post-tACS. Beta-band CMC increased in the tACS group at retention day 1 compared with post-tACS. Changes in CMC but not IMC were correlated with performance 1 and 7 days following practice. This study shows that tACS applied at beta-band CMC frequency improves consolidation following visuomotor practice and increases beta-band CMC and IMC. We propose that oscillatory beta activity in the corticospinal system may facilitate consolidation of the motor skill.
Identification of Differentially Methylated miRNA Genes During Compatible and Incompatible Interactions Between Soybean and Soybean Cyst Nematode
Authors: Rambani Aditi , Hu Yanfeng , Piya Sarbottam , Long Miao , Rice J. Hollis , Pantalone Vince , Hewezi Tarek 
Published: August 2020

DNA methylation is a widespread epigenetic mark that affects gene expression and transposon mobility during plant development and stress responses. However, the role of DNA methylation in regulating the expression of microRNA (miRNA) genes remains largely unexplored. Here, we analyzed DNA methylation changes of miRNA genes using a pair of soybean (Glycine max) near-isogenic lines (NILs) differing in their response to soybean cyst nematode (SCN; Heterodera glycines). Differences in global DNA methylation levels over miRNA genes in response to SCN infection were observed between the isogenic lines. miRNA genes with significant changes in DNA methylation levels in the promoter and primary transcript-coding regions were detected in both lines. In the susceptible isogenic line (NIL-S), 82 differentially methylated miRNAs were identified in response to SCN infection whereas, in the resistant isogenic line (NIL-R), only 16 differentially methylated miRNAs were identified. Interestingly, gma-miR5032, gma-miR5043, gma-miR1520b, and gma-2107-ch16 showed opposite methylation patterns in the isogenic lines. In addition, the miRNA paralogs gma-miR5770a and gma-miR5770b showed hypermethylation and hypomethylation in NIL-S and NIL-R, respectively. Gene expression quantification of gma-miR5032, gma-miR5043, gma-miR1520b, and gma-miR5770a/b and their confirmed targets indicated a role of DNA methylation in regulating miRNA expression and, thus, their targets upon SCN infection. Furthermore, overexpression of these four miRNAs in NIL-S using transgenic hairy root system enhanced plant resistance to SCN to various degrees with a key role observed for miR5032. Together, our results provide new insights into the role of epigenetic mechanisms in controlling miRNA regulatory function during SCN–soybean interactions. [Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Impaired learning and memory ability induced by a bilaterally hippocampal injection of streptozotocin in mice: involved with the adaptive changes of synaptic plasticity
Authors: Qi Congcong , Chen Xingxing , Gao Xinran , Xu Jingxian , Liu Sen , Ge Jinfang 
Published: August 2020

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, psychiatric symptoms and behavioral disorders, resulting in disability and loss of self-sufficiency.ObjectiveTo establish an AD mice model, investigate the behavioral performance, and explore the potential mechanism.MethodsStreptozotocin (STZ, 3 mg/kg) was microinjected bilaterally into the dorsal hippocampus of C57BL /6 mice to establish the AD model. Behavioral changes (anhedonia and despair, balance and motor coordination, locomotion, and learning and memory) were examined and the serum concentrations of insulin and nesfatin-1 were measured by ELISA. The activation of hippocampal microglia was assessed by immunohistochemistry and the protein expression of several molecular associated with the regulation of synaptic plasticity in the hippocampus and the prefrontal cortex (PFC) was detected via western blotting.ResultsThe STZ model mice showed a slower bodyweight gain and higher serum concentration of insulin and nesfatin-1. Although there was no significant difference between groups with regard to the ability of balance and motor coordination, the model mice presented a decline of spontaneous movement and exploratory behavior, together with an impairment of learning and memory ability. Increased activated microglia was aggregated in the hippocampal dentate gyrus of model mice. Moreover, the protein expression of NMDAR2A, NMDAR2B, SynGAP, PSD95, BDNF, and p-β-catenin/β-catenin were remarkably decreased in the hippocampus and the PFC of model mice, and the expression of p-GSK-3β (ser9)/GSK-3β were reduced in the hippocampus.ConclusionA bilateral hippocampal microinjection of STZ could successfully duplicate an AD mice model, as indicated by the impaired learning and memory and the alternated synaptic plasticity, together with the hyperactive inflammatory response in the hippocampus and the imbalanced abundance of serum insulin and nesfatin-1. Apart from these, the mechanism might be associated with the imbalanced expression of the key proteins of Wnt signaling pathway in the hippocampus and the PFC.Graphical abstract
The structural and functional connectivity neural underpinnings of body image
Authors: Moayedi Massieh , Noroozbahari Nasim , Hadjis Georgia , Themelis Kristy , Salomons Tim V. , Newport Roger , Lewis Jennifer 
Published: August 2020

AbstractHow we perceive our bodies is fundamental to our self-consciousness and our experience in the world. There are two types interrelated internal body representations—a subjective experience of the position of a limb in space (body schema) and the subjective experience of the shape and size of the limb (body image). Body schema has been extensively studied, but there is no evidence of the brain structure and network dynamics underpinning body image. Here, we provide the first evidence for the extrastriate body area (EBA), a multisensory brain area, as the structural and functional neural substrate for body shape and size. We performed a multisensory finger-stretch illusion that elongated the index finger. EBA volume and functional connectivity to the posterior parietal cortex are both related to the participants’ susceptibility to the illusion. Taken together, these data suggest that EBA structure and connectivity encode body representation and body perception disturbances.
Genotype & Phenotype in Lowe Syndrome: SpecificOCRL1patient mutations differentially impact cellular phenotypes
Authors: Ramadesikan Swetha , Skiba Lisette , Lee Jennifer , Madhivanan Kayalvizhi , Sarkar Daipayan , De La Fuente Agustina , Hanna Claudia B. , Terashi Genki , Hazbun Tony , Kihara Daisuke , Aguilar R. Claudio 
Published: August 2020

ABSTRACTLowe Syndrome (LS) is a lethal genetic disorder caused by mutations in theOCRL1gene which encodes the lipid 5’ phosphatase Ocrl1. Patients exhibit a characteristic triad of symptoms including eyes, brain and kidneys abnormalities with renal failure as the most common cause of premature death. Over 200OCRL1mutations have been identified in LS, but their specific impact on cellular processes is unknown. Despite observations of heterogeneity in patient symptom severity, there is little understanding of the correlation between genotype and its impact on phenotype.Here, we show that different mutations had diverse effects on protein localization and on triggering LS cellular phenotypes. In addition, some mutations affecting specific domains imparted unique characteristics to the resulting mutated protein. We also propose that certain mutations conformationally affect the 5’-phosphatase domain of the protein, resulting in loss of enzymatic activity and causing common and specific phenotypes.This study is the first to show the differential effect of patient 5’-phosphatase mutations on cellular phenotypes and introduces a conformational disease component in LS. This work provides a framework that can help stratify patients as well as to produce a more accurate prognosis depending on the nature and location of the mutation within theOCRL1gene.
Genome-wide Prediction of Small Molecule Binding to Remote Orphan Proteins Using Distilled Sequence Alignment Embedding
Authors: Cai Tian , Lim Hansaim , Abbu Kyra Alyssa , Qiu Yue , Nussinov Ruth , Xie Lei 
Published: August 2020

AbstractEndogenous or surrogate ligands of a vast number of proteins remain unknown. Identification of small molecules that bind to these orphan proteins will not only shed new light into their biological functions but also provide new opportunities for drug discovery. Deep learning plays an increasing role in the prediction of chemical-protein interactions, but it faces several challenges in protein deorphanization. Bioassay data are highly biased to certain proteins, making it difficult to train a generalizable machine learning model for the proteins that are dissimilar from the ones in the training data set. Pre-training offers a general solution to improving the model generalization, but needs incorporation of domain knowledge and customization of task-specific supervised learning. To address these challenges, we develop a novel protein pre-training method, DIstilled Sequence Alignment Embedding (DISAE), and a module-based fine-tuning strategy for the protein deorphanization. In the benchmark studies, DISAE significantly improves the generalizability and outperforms the state-of-the-art methods with a large margin. The interpretability analysis of pre-trained model suggests that it learns biologically meaningful information. We further use DISAE to assign ligands to 649 human orphan G-Protein Coupled Receptors (GPCRs) and to cluster the human GPCRome by integrating their phylogenetic and ligand relationships. The promising results of DISAE open an avenue for exploring the chemical landscape of entire sequenced genomes.
Small molecule FGF23 inhibitors increase serum phosphate and improve skeletal abnormalities inHypmice
Authors: Xiao Zhousheng , Liu Jiawang , Liu Shih-Hsien , Petridis Loukas , Cai Chun , Cao Li , Wang Guangwei , Chin Ai Lin , Cleveland Jacob W. , Ikedionwu Munachi O. , Carrick Jesse D. , Smith Jeremy C. , Quarles L. Darryl 
Published: August 2020

ABSTRACTFibroblast growth factor 23 (FGF23) is a bone-derived hormone that binds to binary FGFR/α-Klotho receptor complexes in the kidney tubules to inhibit phosphate reabsorption and 1,25(OH)2D production. Excess FGF23 causes X-linked hypophosphatemia (XLH) and tumor induced osteomalacia (TIO). Recently, Burosumab, an FGF23 blocking antibody, was approved for treating these hypophosphatemic disorders. A small molecule inhibitor that specifically binds to FGF23 to prevent activation of FGFR/α-Klotho complexes has potential advantages over a systemically administered FGF23 blocking antibody. We previously identified the small molecule ZINC13407541 (N-[[2-(2-phenylethenyl)cyclopenten-1-yl]methylidene]hydroxylamine) as a therapeutic lead FGF23 antagonist. Additional structure-activity studies developed a series of ZINC13407541 analogues with enhanced drug-like properties. In this study, we tested in a pre-clinicalHypmouse homologue of XLH a direct connect analogue (8n) [(E)-2-(4-(tert-butyl)phenyl)cyclopent-1-ene-1-carbaldehyde oxime] that exhibited the greatest stability in microsomal assays, and13a[(E)-2-((E)-4-methylstyryl)benzaldehyde oxime] that exhibited increasedin vitropotency. We found that pharmacological inhibition of FGF23 with either of these compounds blocked FGF23 signaling and significantly increased serum phosphate and 1,25(OH)2D concentrations inHypmice. Long-term parenteral treatment with8nor13aalso enhanced linear bone growth, increased mineralization of bone, and narrowed the growth plate inHypmice. The more potent13acompound showed greater therapeutic efficacy inHypmice. Further optimization of these FGF23 inhibitors may lead to versatile drugs to treat FGF23-mediated disorders.
Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens
Authors: Renuse Santosh , Vanderboom Patrick M. , Maus Anthony D. , Kemp Jennifer V. , Gurtner Kari M. , Madugundu Anil K. , Chavan Sandip , Peterson Jane A. , Madden Benjamin J. , Mangalaparthi Kiran K. , Mun Dong-Gi , Singh Smrita , Kipp Benjamin R. , Dasari Surendra , Singh Ravinder J. , Grebe Stefan K. , Pandey Akhilesh 
Published: August 2020

ABSTRACTThe COVID-19 pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has overwhelmed health systems worldwide and highlighted limitations of diagnostic testing. Several types of diagnostics including RT-PCR-based assays, antigen detection by lateral flow assays and antibody-based assays have been developed and deployed in a short time. However, many of these assays are lacking in sensitivity and/or specificity. Here, we describe an immunoaffinity purification followed by high resolution mass spectrometry-based targeted assay capable of detecting viral antigen in nasopharyngeal swab samples of SARS-CoV-2 infected individuals. Based on our discovery experiments using purified virus, recombinant viral protein and nasopharyngeal swab samples from COVID-19 positive patients, nucleocapsid protein was selected as a target antigen. We then developed an automated antibody capture-based workflow coupled to targeted high-field asymmetric ion mobility spectrometry (FAIMS) - parallel reaction monitoring (PRM) assays on an Orbitrap Exploris 480 mass spectrometer. An ensemble machine learning-based model for determining COVID-19 positive samples was created using fragment ion intensities in the PRM data. This resulted in 97.8% sensitivity and 100% specificity with RT-PCR-based molecular testing as the gold standard. Our results demonstrate that direct detection of infectious agents from clinical samples by mass spectrometry-based assays have potential to be deployed as diagnostic assays in clinical laboratories.
Threshold concentration and random collision determine the growth of the phase-separated huntingtin inclusion from a stable core
Authors: Pei Sen , Swayne Theresa C. , Morris Jeffrey F. , Emtage Lesley 
Published: August 2020

AbstractThe processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases. InS. cerevisiae, inclusion bodies formed by mutant huntingtin have characteristics of phase-separated compartments: they are mobile, ovoid, and the contents are diffusible. We have used molecular genetics and quantitative confocal microscopy to probe the relationship between concentration and inclusion growth in vivo. Our analysis and modeling of the growth of mutant huntingtin inclusion bodies (mHtt IBs) suggests that there is a cytoplasmic threshold concentration that triggers the formation of an IB, regardless of proteasome capacity, and that reduction in cytoplasmic mHtt causes IBs to shrink. These findings confirm that the IB is a phase-separated compartment that continuously exchanges material with the cytoplasm. The growth rate of the IB is most consistent with a model in which material is incorporated through collision with the IB. A small remnant of the IB is relatively long-lasting, suggesting that the IB contains a core that is structurally distinct, and which may serve to nucleate it.
Plumbagin and oridonin reveal new CRM1 binding sites and NES-binding groove features
Authors: Lei Yuqin , Li Yuling , Tan Yuping , Jia Da , Sun Qingxiang 
Published: August 2020

AbstractCRM1 is an important drug target in diseases such as cancer and viral infection. Plumbagin and oridonin, the herbal ingredients with known anti-cancer activities, were reported to inhibit CRM1-mediated nuclear export. However, their modes of CRM1 inhibition are unclear. Here, a multi-mutant of yeast CRM1 was engineered to enable the crystallization of these two small molecules in CRM1’s NES-binding groove. Each structure showed three inhibitor-binding sites, among which two are conserved in humans. Besides the known binding site, another site also participated in oridonin and plumbagin’s CRM1 inhibition. While the plumbagin-bound NES groove resembled the NES-bound groove state, the oridonin-bound groove revealed for the first time a more open NES groove, which may potentially improve cargo-loading through a capture-and-tighten mechanism. Our work thus provides a tool for CRM1 inhibitor crystallization, new insights of CRM1-cargo interaction, and a structural basis for further development of these or other CRM1 inhibitors.