bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic Status, Biological Aging, and Memory in a Diverse National Sample of Older US Men and Women
Authors: Avila Justina F. , Turney Indira C. , Esie Precious , Vonk Jet M. J. , Weir Vanessa R. , Belsky Daniel W. , Manly Jennifer J. 
Published: June 2021

AbstractImportanceExposure to socioeconomic disadvantage is associated with rapid cognitive aging. Biological aging, the progressive loss of system integrity that occurs as we age is proposed as a modifiable process mediating this health inequality.ObjectiveTo test the hypothesis that socioeconomic disparities in cognitive aging in older adults is explained by accelerated biological aging.DesignObservational cohort study.SettingU.S. Health and Retirement Study DNA-methylation sub-study.ParticipantsN=3,648 (49% male) adults aged 50-100 (M=70, SD=10) with DNA methylation data.ExposuresSocioeconomic status (SES) was measured from years of education and household wealth. The extent and pace of biological aging were quantified using three DNA-methylation measures: PhenoAge, GrimAge, and DunedinPoAm.Main Outcomes and MeasuresCognitive aging was measured from repeated longitudinal assessments of immediate and delayed word recall. Latent growth curve modeling estimated participants’ level of memory performance and rate of decline over 2-11 follow-up assessments spanning 2-20 years. Models were estimated to assess whether the relationship between SES and memory trajectories was mediated by biological aging.ResultsOlder adults with lower SES had lower memory performance, faster decline and exhibited accelerated biological aging (SES β=.33, 99% CI[.30-.36], biological-aging measure effect size associations ranged from .08 to .20). Accelerated biological aging was associated with decreased memory performance and faster memory decline (effect-size range .03 to .18). Higher SES was associated with slower biological aging for White and Black men and women, but not Latinx participants. The relationship between biological aging measures and memory was weaker for Black and Latinx participants compared with White people. In mediation analysis, biological aging accounted for 3-9% of the SES-memory gradient in White participants. There was no evidence of mediation in Black or Latinx participants.Conclusions and RelevanceAmong a national sample of older adults, DNA-methylation measures of biological aging were associated with memory trajectories in White, but not Black or Latinx older adults. These results challenge the assumption that DNA-methylation biomarkers of aging that were developed in primarily White people can quantify aging processes affecting cognition in Black and Latinx older adults.
Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia
Authors: Chekuri Anil , Logan Emily M. , Krauson Aram J. , Salani Monica , Ackerman Sophie , Kirchner Emily G. , Bolduc Jessica M. , Wang Xia , Dietrich Paula , Dragatsis Ioannis , Vandenberghe Luk H. , Slaugenhaupt Susan A. , Morini Elisabetta 
Published: June 2021

AbstractFamilial dysautonomia (FD) is an autosomal recessive neurodegenerative disease caused by a splicing mutation in the gene encoding Elongator complex protein 1 (ELP1, also known asIKBKAP). This mutation results in tissue-specific skipping of exon 20 with a corresponding reduction of ELP1 protein, predominantly in the central and peripheral nervous system. Although FD patients have a complex neurological phenotype caused by continuous depletion of sensory and autonomic neurons, progressive visual decline leading to blindness is one of the most problematic aspect of the disease, as it severely affects their quality of life. To better understand the disease mechanism as well as to test thein vivoefficacy of targeted therapies for FD, we have recently generated a novel phenotypic mouse model,TgFD9; Elp1∆20/flox. This mouse exhibits most of the clinical features of the disease and accurately recapitulates the tissue-specific splicing defect observed in FD patients. Driven by the dire need to develop therapies targeting retinal degeneration in FD, herein, we comprehensively characterized the progression of the retinal phenotype in this mouse, and we demonstrated that it is possible to correctELP1splicing defect in the retina using the splicing modulator compound (SMC) BPN-15477.
Mapping tree species for restoration potential resilient to climate change
Authors: van Tiel Nina , Lyu Lisha , Fopp Fabian , Brun Philipp , van den Hoogen Johan , Karger Dirk Nikolaus , Zimmermann Niklaus E. , Crowther Thomas W. , Pellissier Loïc 
Published: June 2021

AbstractThe restoration of forest ecosystems is associated with key benefits for biodiversity and ecosystem services. Where possible, ecosystem restoration efforts should be guided by a detailed knowledge of the native flora to regenerate ecosystems in a way that benefits natural biodiversity, ecosystem services, and nature’s contribution to people. Machine learning can map the ecological suitability of tree species globally, which then can guide restoration efforts, especially in regions where knowledge about the native tree flora is still insufficient. We developed an algorithm that combines ecological niche modelling and geographic distributions that allows for the high resolution (1km) global mapping of the native range and suitability of 3,987 tree species under current and future climatic conditions. We show that in most regions where forest cover could be potentially increased, heterogeneity in ecological conditions and narrow species niche width limit species occupancy, so that in several areas with reforestation potential, a large amount of potentially suitable species would be required for successful reforestation. Local tree planting efforts should consider a wide variety of species to ensure that the equally large variety of ecological conditions can be covered. Under climate change, a large fraction of the surface for restoration will suffer significant turnover in suitability, so that areas that are suitable for many species under current conditions will not be suitable in the future anymore. Such a turnover due to shifting climate is less pronounced in regions containing species with broader geographical distributions. This indicates that if restoration decisions are solely based on current climatic conditions, a large fraction of the restored area will become unsuitable in the future. Decisions on forest restoration should therefore take the niche width of a tree species into account to mitigate the risk of climate-driven ecosystem degradation.
Drug Repurposing for the SARS-CoV-2 Papain-Like Protease
Authors: Cho Chia-Chuan D. , Li Shuhua G. , Yang Kai S. , Lalonde Tyler J. , Yu Ge , Qiao Yuchen , Xu Shiqing , Liu Wenshe Ray 
Published: June 2021

ABSTRACTAs the pathogen of COVID-19, SARS-CoV-2 encodes two essential cysteine proteases that process the pathogen’s two large polypeptide translates ORF1a and ORF1ab in human host cells to form 15 functionally important, mature nonstructural proteins. One of the two enzymes, papain-like protease or PLpro, also possesses deubiquitination and deISGylation activities that suppresses host innate immune responses toward SARS-CoV-2 infection. Therefore, PLpro is a potential COVID-19 drug target. To repurpose drugs for PLpro, we experimentally screened 33 deubiquitinase and 37 cysteine protease inhibitors on their inhibition of PLpro. Our results showed that 15 deubiquitinase and 1 cysteine protease inhibitors exhibit potent inhibition of PLpro at 200μM. More comprehensive characterizations revealed 7 inhibitors GRL0617, SJB2-043, TCID, DUB-IN-1, DUB-IN-3, PR-619, and S130 with an IC50value below 60μM and four inhibitors GRL0617, SJB2-043, TCID, and PR-619 with an IC50value below 10μM. Among four inhibitors with an IC50value below 10μM, SJB2-043 is the most unique in that it doesn’t fully inhibit PLpro but has an outstanding IC50value of 0.56μM. SJB2-043 likely binds to an allosteric site of PLpro to convene its inhibition effect, which needs to be further investigated. As a pilot study, the current work indicates that COVID-19 drug repurposing by targeting PLpro holds promises but in-depth analysis of repurposed drugs is necessary to avoid omitting allosteric inhibitors.
When to be vaccinated? What to consider? Modelling decision-making and time preference for COVID-19 vaccine through a conjoint experiment approach
Authors: Yuen Samson W.H. , Yue Ricci P.H. , Lau Bobo H.B. , Chan Cecilia L. W. , Ng Siu-Man 
Published: June 2021

AbstractHow do citizens choose COVID-19 vaccines, and when do they wish to be vaccinated? A choice-based conjoint experiment was fielded in Hong Kong to examine factors that shape citizens’ preference toward COVID-19 vaccines and their time preference to be vaccinated, which is overlooked in extant literature. Results suggest people are most concerned about vaccines’ efficacy and severe side-effects, and that cash incentives are not useful in enhancing vaccine appeal. The majority of respondents show low intention for immediate vaccination, and many of them want to delay their vaccination. Further analysis shows that their time preference is shaped more by respondent characteristics than vaccine attributes. In particular, confidence in the vaccine, trust in government, and working in high-risk professions are associated with earlier timing for vaccine uptake. Meanwhile, forced COVID testing would delay vaccination. The findings offer a novel view in understanding how people decide whether and when to receive new vaccines, which have pivotal implications for a head start of any mass vaccination programs.HighlightsPeople are most concerned about vaccines’ efficacy and severe side-effects when choosing COVID-19 vaccinesCash incentives are not useful in enhancing vaccines’ appealTime preference of vaccination is shaped more by respondent characteristics than vaccine attributesForced COVID testing might delay vaccination decision
Precise annotation of Drosophila mitochondrial genomes leads to insights into AT-rich regions
Authors: Liang Guangcai , Chang Jia , Yau Tung On , Li Xin , He Bingjun , Ruan Jishou , Bu Wenjun , Gao Shan 
Published: June 2021

AbstractIn the present study, we performed precise annotation of Drosophila melanogaster, D. simulans, D. grimshawi, Bactrocera oleae mitochondrial (mt) genomes by pan RNA-seq analysis. Our new annotations corrected or modified some of the previous annotations and two important findings were reported for the first time, including the discovery of the conserved polyA(+) and polyA(−) motifs in the control regions (CRs) of insect mt genomes and the adding of CCAs to the 3’ ends of two antisense tRNAs in D. melanogaster mt genome. Using PacBio cDNA-seq data from D. simulans, we precisely annotated the Transcription Initiation Sites (TISs) of the mt Heavy and Light strands in Drosophila mt genomes and reported that the polyA(+) and polyA(−) motifs in the CRs are associated with TISs. The discovery of the conserved polyA(+) and polyA(−) motifs provides insights into many polyA and polyT sequences in CRs of insect mt genomes, leading to reveal the mt transcription and its regulation in invertebrates. In addition, we provided a high-quality, well-curated and precisely annotated D. simulans mt genome (GenBank: MN611461), which should be included into the NCBI RefSeq database to replace the current reference genome NC_005781.
Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorder
Authors: Okhuijsen-Pfeifer C. , van der Horst M.Z. , Bousman C.A. , Lin B. , van Eijk K.R. , Ripke S. , Ayhan Y. , Babaoglu M.O. , Bak M. , Alink W. , van Beek H. , Beld E. , Bouhuis A. , Edlinger M. , Erdogan I.M. , Ertuğrul A. , Yoca G. , Everall I.P. , Görlitz T. ,   GROUP Genetic Risk and Outcome of Psychosis investigators, Grootens K.P. , Gutwinski S. , Hallikainen T. , Jeger-Land E. , de Koning M. , Lähteenvuo M. , Legge S.E. , Leucht S. , Morgenroth C. , Müderrisoğlu A. , Narang A. , Pantelis C. , Pardiñas A.F. , Oviedo-Salcedo T. , Schneider-Thoma J. , Schreiter S. , Repo-Tiihonen E. , Tuppurainen H. , Veereschild M. , Veerman S. , de Vos M. , Wagner E. , Cohen D. , Bogers J.P.A.M. , Walters J.T.R. , Anil Yağcıoğlu A.E. , Tiihonen J. , Hasan A. , Luykx J.J. 
Published: June 2021

AbstractClozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N=684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p=1.03×10−3; R2=1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p=0.01; R2=0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p=6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p=8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p=3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
Anti-spike protein receptor-binding domain IgG levels after COVID-19 infection or vaccination against SARS-CoV-2 in a seroprevalence study
Authors: Soeorg Hiie , Jõgi Piia , Naaber Paul , Ottas Aigar , Toompere Karolin , Lutsar Irja 
Published: June 2021

AbstractPurposeIn a country-wide seroprevalence study of COVID-19 in Estonia we aimed to determine the seroprevalence and the dynamics of IgG against SARS-CoV-2 after vaccination or positive PCR-test.MethodsLeftover blood samples were selected between February 8 to March 25, 2021, by SYNLAB Estonia from all counties and age groups (0-9, 10-19, 20-59, 60-69, 70-79, 80-100 years) proportionally to the whole Estonian population and tested for IgG against SARS-CoV-2 spike protein receptor-binding domain (anti-S-RBD IgG) using Abbott SARS-CoV-2 IgG II Quant assay. Antibody levels after positive PCR-test or vaccination were described by nonlinear model.ResultsA total of 2517 samples were tested. Overall seroprevalence (95% CI) was 20.1% (18.5-21.7%), similar in all age groups. If all individuals vaccinated with the first dose at least 14 days before antibody measurement were assumed to be seronegative, the overall seroprevalence was 15.8% (14.4-17.3%), 4-fold larger than the proportion of confirmed COVID-19 cases. According to nonlinear models, age increased anti-S-RBD IgG production after positive PCR-test but decreased after vaccination. The peak of anti-S-RBD IgG in a 52-year-old (median age of PCR-positive and/or vaccinated individuals) was significantly higher after vaccination compared with positive PCR-test (22082 (12897…26875) vs 6732 (2321…8243) AU/mL), but half-life was similar (26.5 (6.9…46.1) vs 38.3 (8.2…68.5) days).ConclusionOne year after the start of COVID-19 pandemic the actual prevalence of infection is still underestimated compared with confirmed COVID-19 cases, underlining the importance of seroepidemiological studies. Older individuals have lower anti-S-RBD IgG level after vaccination, but similar decline rate to younger.
Patterns of gene expression in pollen of cotton (Gossypium hirsutum) indicate down-regulation as a feature of thermotolerance
Authors: Masoomi-Aladizgeh Farhad , McKay Matthew J. , Asar Yasmin , Haynes Paul A. , Atwell Brian J. 
Published: June 2021

SUMMARYReproductive performance in plants is impaired as maximum temperatures consistently approach 40°C. However, the timing of heatwaves critically affects their impact. We studied the molecular responses of cotton male reproductive stages, to investigate the vulnerability of maturing pollen to high temperature. Tetrads, uninucleate and binucleate microspores, and mature pollen were subjected to SWATH-MS and RNA-seq analyses after exposure to 38/28°C (day/night) for 5 days. The results indicated that molecular signatures were down-regulated over developmental stages in response to heat. This was more evident in leaves where three-quarters of differentially changed proteins were decreased in abundance. Functional analysis showed that translation of genes increased in tetrads after exposure to heat; however, the reverse pattern was observed in mature pollen and leaves. Proteins involved in transport were highly abundant in tetrads, whereas in later stages of development and leaves, heat suppressed cell-to-cell communication. Moreover, a large number of heat shock proteins (HSPs) were identified in heat-affected tetrads, but these proteins were less abundant in mature pollen and leaves. We speculate that the sensitivity of tetrad cells to heat is related to increased activity of translation involved in non-essential pathways. Molecular signatures during pollen development after heatwaves provide markers for future genetic improvement.
Cyclic Microchip Assay for Measurement of Hundreds of Functional Proteins in Single Neurons
Authors: Yang Liwei , Ball Avery , Liu Jesse , Jain Tanya , Li Yue-Ming , Wang Jun 
Published: June 2021

AbstractProteins are responsible for nearly all cell functions throughout cellular life. To date, the molecular functions of hundreds of proteins have been studied as they are critical to cellular processes. Those proteins are varied dramatically at different statuses and differential stages of the cells even in the same tissue. The existing single-cell tools can only analyze dozens of proteins and thus have not been able to fully characterize a cell yet. Herein, we present a single-cell cyclic multiplex in situ tagging (CycMIST) technology that affords the comprehensive functional proteome profiling of single cells. It permits multiple, separate rounds of multiplex assays of the same single cells on a microchip where each round detects 40-50 proteins. A decoding process is followed to assign protein identities and quantify protein detection signals. We demonstrate the technology on a neuron cell line by detecting 182 proteins that includes surface makers, neuron function proteins, neurodegeneration markers, signaling pathway proteins and transcription factors. Further study on 5XFAD mouse, an Alzheimer’s Disease (AD) model, cells validate the utility of our technology which reveals the deep heterogeneity of brain cells. Through comparison with control mouse cells, the differentially expressed proteins in the AD mouse model have been detected. The single-cell CycMIST technology can potentially analyze the entire functional proteome spectrum, and thus it may offer new insights into cell machinery and advance many fields including systems biology, drug discovery, molecular diagnostics, and clinical studies.
NOCICEPTRA: Gene and microRNA signatures and their trajectories characterizing human iPSC-derived nociceptor maturation
Authors: Zeidler Maximilian , Kummer Kai K. , Schöpf Clemens L. , Kalpachidou Theodora , Kern Georg , Cader M. Zameel , Kress Michaela 
Published: June 2021

AbstractNociceptors are primary afferent neurons serving the reception of acute pain but also the transit into maladaptive pain disorders. Since native human nociceptors are hardly available for mechanistic functional research, and rodent models do not necessarily mirror human pathologies in all aspects, human iPSC-derived nociceptors (iDN) offer superior advantages as a human model system. Unbiased mRNA::microRNA co-sequencing, immunofluorescence staining and qPCR validations, revealed expression trajectories as well as miRNA target spaces throughout the transition of pluripotent cells into iDNs. mRNA and miRNA candidates emerged as regulatory hubs for neurite outgrowth, synapse development and ion channel expression. The exploratory data analysis tool NOCICEPTRA is provided as a containerized platform to retrieve experimentally determined expression trajectories, and to query custom gene sets for pathway and disease enrichments. Querying NOCICEPTRA for marker genes of cortical neurogenesis revealed distinct similarities and differences for cortical and peripheral neurons. The platform provides a public domain neuroresource to exploit the entire data sets and explore miRNA and mRNA as hubs regulating human nociceptor differentiation and function.
Complexin-1 regulated transition in the assembly of single neuronal SNARE complex
Authors: Hao Tongrui , Feng Nan , Gong Fan , Liu Jiaquan , Ma Lu , Ren Yu-Xuan 
Published: June 2021

ABSTRACTNeurotransmitter release is mediated by the synaptic vesicle exocytosis. Important proteins in this process have been identified including the molecular machine Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, and other regulators. Complexin (Cpx) is one of the vital regulators in this process. The functions of Cpx are proposed to maintain a proper primed vesicle pool by preventing its premature depletion, which facilitates the vesicle fusion in the presence of Ca2+. However, the molecular mechanism remains unclear. Using dual-trap optical tweezers, we detected the interaction of complexin-1 (CpxI) with SNARE. We found that the CpxI stabilizes partially folded SNARE complexes by competing with C-terminal of Vamp protein and interacting with the C-terminal of t-SNARE complex.
Robust fault-tolerant attitude control of spacecraft using hybrid actuators
Authors: Xu Yiqi 
Published: June 2021

Purpose
This paper aims to address the spacecraft attitude control problem using hybrid actuators in the presence of actuator saturation, uncertainties and faults, inertia uncertainties and external disturbances.

Design/methodology/approach
A hybrid actuator configuration is used where thrusters are engaged for rapid attitude maneuvers, while reaction wheels (RWs) are used for fine pointing.

Findings
The key advantages are two-fold: a finite-time high-level controller is designed to produce the three-axis virtual control torques; an online robust control allocation (RobCA) scheme is proposed to redistribute virtual control signals to the actuators with taking into account the actuator saturation, uncertainties and faults; and the RobCA scheme allows a smooth switch between thrusters and RWs, which handles the inaccuracy problem of thrusters and saturation problem of RWs.

Practical implications
An online RobCA algorithm is designed that maps the total control demands onto individual actuator settings and allows a smooth switch between thrusters and RWs. Simulation results show the effectiveness of the proposed control strategy.

Originality/value
This work may be used on modern space missions, which impose higher requirements on smooth switching of spacecraft thrusters and RWs.