bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning Prediction of Biomarkers from SNPs and of Disease Risk from Biomarkers in the UK Biobank
Authors: Widen Erik , Raben Timothy G. , Lello Louis , Hsu Stephen D.H. 
Published: April 2021

AbstractWe use UK Biobank data to train predictors for 48 blood and urine markers such as HDL, LDL, lipoprotein A, glycated haemoglobin, … from SNP genotype. For example, our predictor correlates ∼ 0.76 with lipoprotein A level, which is highly heritable and an independent risk factor for heart disease. This may be the most accurate genomic prediction of a quantitative trait that has yet been produced (specifically, for European ancestry groups). We also train predictors of common disease risk using blood and urine biomarkers alone (no DNA information). Individuals who are at high risk (e.g., odds ratio of>5x population average) can be identified for conditions such as coronary artery disease (AUC ∼ 0.75), diabetes (AUC ∼ 0.95), hypertension, liver and kidney problems, and cancer using biomarkers alone. Our atherosclerotic cardiovascular disease (ASCVD) predictor uses ∼ 10 biomarkers and performs in UKB evaluation as well as or better than the American College of Cardiology ASCVD Risk Estimator, which uses quite different inputs (age, diagnostic history, BMI, smoking status, statin usage, etc.). We compare polygenic risk scores (risk conditional on genotype: (risk score | SNPs)) for common diseases to the risk predictors which result from the concatenation of learned functions (risk score | biomarkers) and (biomarker | SNPs).
Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids
Authors: Inoue Takayoshi , Kuwano Tetsuya , Uehara Yuya , Yano Michiko , Oya Naoki , Hachiya Akira , Takahashi Yoshito , Ota Noriyasu , Murase Takatoshi 
Published: April 2021

AbstractNon-invasive acquisition of mRNA data from the skin would be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable human mRNAs exist in SSLs, where sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNAs, and our results revealed that SSL-RNAs predominantly contained mRNAs derived from sebaceous glands, epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal differentiation-related genes, consistent with the results of previous reports. Further, we found that lipid synthesis-related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is promising to understand the pathophysiology of skin diseases.
Transcriptomes across fertilization and seed development in the water lilyNymphaea thermarum(Nymphaeales) reveal dynamic expression of DNA and histone methylation modifiers
Authors: Povilus Rebecca A. , Friedman William E. 
Published: April 2021

AbstractStudies of gene expression during seed development have been performed for a growing collection of species from a phylogenetically broad sampling of flowering plants (angiosperms). However, attention has mostly been focused on crop species or a small number of ‘model’ systems. Information on gene expression during seed development is minimal for those angiosperm lineages whose origins predate the divergence of monocots and eudicots. In order to provide a new perspective on the early evolution of seed development in flowering plants, we sequenced transcriptomes of whole ovules and seeds from three key stages of reproductive development in the waterlilyNymphaea thermarum, an experimentally-tractable member of the Nymphaeales. We first explore general patterns of gene expression, beginning with mature ovules and continuing through fertilization into early- and mid-seed development. We then examine the expression of genes associated with DNA and histone methylation – processes known to be essential for development in distantly-related and structurally-divergent monocots and eudicots. Around 60% of transcripts putatively homologous to DNA and histone methylation modifiers are differentially expressed during seed development inN. thermarum, suggesting that the importance of dynamic epigenetic patterning during seed development dates to the earliest phases of angiosperm evolution. However, genes involved in establishing, maintaining, and removing methylation marks associated with genetic imprinting show a mix of conserved and unique expression patterns betweenN. thermarumand other flowering plants. Our data suggests that the regulation of imprinting has likely changed throughout angiosperm evolution, and furthermore identifies genes that merit further characterization in any angiosperm system.
Cell-type specific circadian bioluminescence rhythms inDbpreporter mice
Authors: Smith Ciearra B. , van der Vinne Vincent , McCartney Eleanor , Stowie Adam C. , Leise Tanya L. , Martin-Burgos Blanca , Molyneux Penny C. , Garbutt Lauren A. , Brodsky Michael H. , Davidson Alec J. , Harrington Mary E. , Dallmann Robert , Weaver David R. 
Published: April 2021

AbstractCircadian rhythms are endogenously generated physiological and molecular rhythms with a cycle length of about 24 h. Bioluminescent reporters have been exceptionally useful for studying circadian rhythms in numerous species. Here, we report development of a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein (Dbp). In this line of mice, firefly luciferase is expressed from theDbplocus in aCre-recombinase-dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. A mouse line in which luciferase expression wasCre-independent was also generated. TheDbpreporter alleles do not alterDbpgene expression rhythms in liver or circadian locomotor activity rhythms.In vivoandex vivostudies show the utility of the reporter alleles for monitoring rhythmicity. Our studies reveal cell-type specific characteristics of rhythms among neuronal populations within the suprachiasmatic nucleiex vivo.In vivostudies showDbp-driven bioluminescence rhythms in the liver ofAlbumin-Cre;DbpKI/+“liver reporter” mice. After a shift of the lighting schedule, locomotor activity achieved the proper phase relationship with the new lighting cycle more rapidly than hepatic bioluminescence did. As previously shown, restricting food access to the daytime altered the phase of hepatic rhythmicity. Our model allowed assessment of the rate of recovery from misalignment once animals were provided with foodad libitum. These studies confirm the previously demonstrated circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.
Distinctin vivodynamics of excitatory synapses onto cortical pyramidal neurons and inhibitory interneurons
Authors: Melander Joshua B. , Nayebi Aran , Jongbloets Bart C. , Fortin Dale A. , Qin Maozhen , Ganguli Surya , Mao Tianyi , Zhong Haining 
Published: April 2021

SUMMARYCortical function relies on the balanced activation of excitatory and inhibitory neurons. However, little is known about the organization and dynamics of shaft excitatory synapses onto cortical inhibitory interneurons, which cannot be easily identified morphologically. Here, we fluorescently visualize the excitatory postsynaptic marker PSD-95 at endogenous levels as a proxy for excitatory synapses onto layer 2/3 pyramidal neurons and parvalbumin-positive (PV+) inhibitory interneurons in the mouse barrel cortex. Longitudinalin vivoimaging reveals that, while synaptic weights in both neuronal types are log-normally distributed, synapses onto PV+ neurons are less heterogeneous and more stable. Markov-model analyses suggest that the synaptic weight distribution is set intrinsically by ongoing cell type-specific dynamics, and substantial changes are due to accumulated gradual changes. Synaptic weight dynamics are multiplicative, i.e., changes scale with weights, though PV+ synapses also exhibit an additive component. These results reveal that cell type-specific processes govern cortical synaptic strengths and dynamics.
The testis-specific transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in placental mammals
Authors: Özata Deniz M. , Yu Tianxiong , Cecchini Katharine , Mou Haiwei , Arif Amena , Colpan Cansu , Biasini Adriano , Gaitendinov Ildar , de Rooij Dirk G. , Weng Zhiping , Zamore Phillip D. 
Published: April 2021

AbstractIn male mice, the transcription factor (TF) A-MYB initiates reprogramming of gene expression after spermatogonia enter meiosis. We report that A-MYB activatesTcfl5, a testis-specific TF first produced in pachytene spermatocytes. Subsequently, A-MYB and TCFL5 reciprocally reinforce their own transcription to establish an extensive circuit that regulates meiosis. TCFL5 promotes transcription of genes required for mRNA turnover, pachytene piRNA production, meiotic exit, and spermiogenesis. This transcriptional architecture is conserved in rhesus macaque, suggesting TCFL5 plays a central role in meiosis and spermiogenesis in placental mammals.Tcfl5em1/em1mutants are sterile, and spermatogenesis arrests at the mid- or late-pachytene stage of meiosis.
Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan
Authors: Li Cesheng , Yu Ding , Wu Xiao , Liang Hong , Zhou Zhijun , Xie Yong , Li Taojing , Wu Junzheng , Lu Fengping , Feng Lu , Mao Min , Lin Lianzhen , Guo Huanhuan , Yue Shenglan , Wang Feifei , Peng Yan , Hu Yong , Wang Zejun , Yu Jianhong , Zhang Yong , Lu Jia , Ning Haoran , Yang Huichuan , Fu Daoxing , He Yanlin , Zhou Dongbo , Du Tao , Duan Kai , Dong Demei , Deng Kun , Zou Xia , Zhang Ya , Zhou Rong , Gao Yang , Zhang Xinxin , Yang Xiaoming 
Published: April 2021

AbstractTo investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.
Decreased thermal tolerance as a trade-off of antibiotic resistance
Authors: Herren Cristina M. , Baym Michael 
Published: April 2021

AbstractEvolutionary theory predicts that adaptations, including antibiotic resistance, should come with associated fitness costs; yet, many resistance mutations seemingly contradict this prediction by inducing no growth rate deficit. However, most growth assays comparing sensitive and resistant strains have been performed under a narrow range of environmental conditions, which do not reflect the variety of contexts that a pathogenic bacterium might encounter when causing infection. We hypothesized that reduced niche breadth, defined as diminished growth across a diversity of environments, can be a cost of antibiotic resistance. Specifically, we test whether chloramphenicol-resistantEscherichia coliincur disproportionate growth deficits in novel thermal conditions. Here we show that chloramphenicol-resistant bacteria have greater fitness costs at novel temperatures than their antibiotic-sensitive ancestors. In several cases, we observed no resistance cost in growth rate at the historic temperature but saw diminished growth at warmer and colder temperatures. These results were consistent across various genetic mechanisms of resistance. Thus, we propose that decreased thermal niche breadth is an under-documented fitness cost of antibiotic resistance. Furthermore, these results demonstrate that the cost of antibiotic resistance shifts rapidly as the environment changes; these context-dependent resistance costs should select for the rapid gain and loss of resistance as an evolutionary strategy.
The Lithuanian reference genome LT1 - a humande novogenome assembly with short and long read sequence and Hi-C data
Authors: Kim Hui-Su , Blazyte Asta , Jeon Sungwon , Yoon Changhan , Kim Yeonkyung , Kim Changjae , Bolser Dan , Ahn Ji-Hye , Edwards Jeremy S. , Bhak Jong 
Published: April 2021

AbstractWe present LT1, the first high-quality human reference genome from the Baltic States. LT1 is a femalede novohuman reference genome assembly constructed using 57× of ultra-long nanopore reads and 47× of short paired-end reads. We also utilized 72 Gb of Hi-C chromosomal mapping data to maximize the assembly’s contiguity and accuracy. LT1’s contig assembly was 2.73 Gbp in length comprising of 4,490 contigs with an N50 value of 13.4 Mbp. After scaffolding with Hi-C data and extensive manual curation, we produced a chromosome-scale assembly with an N50 value of 138 Mbp and 4,699 scaffolds. Our gene prediction quality assessment using BUSCO identify 89.3% of the single-copy orthologous genes included in the benchmarking set. Detailed characterization of LT1 suggested it has 73,744 predicted transcripts, 4.2 million autosomal SNPs, 974,000 short indels, and 12,330 large structural variants. These data are shared as a public resource without any restrictions and can be used as a benchmark for further in-depth genomic analyses of the Baltic populations.
Co-infection of chickens with H9N2 and H7N9 avian influenza viruses leads to emergence of reassortant H9N9 virus with increased fitness for poultry and enhanced zoonotic potential
Authors: Bhat Sushant , James Joe , Sadeyen Jean-Remy , Mahmood Sahar , Everest Holly J , Chang Pengxiang , Walsh Sarah , Byrne Alexander MP , Mollett Benjamin , Lean Fabian , Sealy Joshua E. , Shelton Holly , Slomka Marek J , Brookes Sharon M , Iqbal Munir 
Published: April 2021

SUMMARYAn H7N9 low pathogenicity avian influenza virus (LPAIV) emerged through genetic reassortment between H9N2 and other LPAIVs circulating in birds in China. This virus causes inapparent clinical disease in chickens, but zoonotic transmission results in severe and fatal disease in humans. We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of G1 lineage that are enzootic in poultry across the Indian sub-continent and the Middle East. Co-infection of chickens with these viruses resulted in emergence of novel reassortant H9N9 viruses carrying genes derived from both H9N2 and H7N9 viruses. These reassortant H9N9 viruses showed significantly increased replication fitness, enhanced pathogenicity in chicken embryos and the potential to transmit via contact among ferrets. Our study highlights that the co-circulation of H7N9 and H9N2 viruses could represent a threat for the generation of novel reassortant viruses with greater virulence in poultry and an increased zoonotic potential.Graphical AbstractIn BriefH9N2 viruses have a high propensity to reassort with other avian influenza viruses. We found that co-infection of chickens with H9N2 and H7N9 led to the emergence of reassortant viruses including the H9N9 subtype. Some reassortant H9N9 viruses exhibited increased replication fitness, increased pathogenicity in the chicken embryo, greater avidity for human and avian cell receptors, lower pH fusion and contact-transmission to ferrets. This study demonstrated the ability of viruses that already exist in nature to exchange genetic material, highlighting the potential emergence of viruses from these subtypes with increased zoonotic potential. There are nine H9 influenza A subtypes carrying different neuraminidase (NA) genes, including H9N9 viruses, while they are not common they do exist in nature as wildtypes (CDC).HighlightsCo-infection of chickens with H7N9 and H9N2 led to emergence of reassortant H9N9 virusesReassortant H9N9 viruses had an increased replication rate in avian and human cellsReassortant H9N9 viruses had a lower pH fusion and significantly higher receptor binding to α 2,3 sialoglycansReassortant H9N9 replicated in ferrets at similar levels compared to H7N9 and transmitted via direct contactFerrets exposed to reassortant H9N9 by aerosol contact were also found to be seropositiveExperimental simulation of events that may occur naturally with circulating viruses has demonstrated the risk of emergence of viruses with increased zoonotic potential.
Cloud robotic grasping of Gaussian mixture model based on point cloud projection under occlusion
Authors: Lin Shifeng , Wang Ning 
Published: April 2021

Purpose
In multi-robot cooperation, the cloud can share sensor data, which can help robots better perceive the environment. For cloud robotics, robot grasping is an important ability that must be mastered. Usually, the information source of grasping mainly comes from visual sensors. However, due to the uncertainty of the working environment, the information acquisition of the vision sensor may encounter the situation of being blocked by unknown objects. This paper aims to propose a solution to the problem in robot grasping when the vision sensor information is blocked by sharing the information of multi-vision sensors in the cloud.

Design/methodology/approach
First, the random sampling consensus algorithm and principal component analysis (PCA) algorithms are used to detect the desktop range. Then, the minimum bounding rectangle of the occlusion area is obtained by the PCA algorithm. The candidate camera view range is obtained by plane segmentation. Then the candidate camera view range is combined with the manipulator workspace to obtain the camera posture and drive the arm to take pictures of the desktop occlusion area. Finally, the Gaussian mixture model (GMM) is used to approximate the shape of the object projection and for every single Gaussian model, the grabbing rectangle is generated and evaluated to get the most suitable one.

Findings
In this paper, a variety of cloud robotic being blocked are tested. Experimental results show that the proposed algorithm can capture the image of the occluded desktop and grab the objects in the occluded area successfully.

Originality/value
In the existing work, there are few research studies on using active multi-sensor to solve the occlusion problem. This paper presents a new solution to the occlusion problem. The proposed method can be applied to the multi-cloud robotics working environment through cloud sharing, which helps the robot to perceive the environment better. In addition, this paper proposes a method to obtain the object-grabbing rectangle based on GMM shape approximation of point cloud projection. Experiments show that the proposed methods can work well.
Turning around accountability
Authors: Li Yingru , McKernan John , Chen Meiyi 
Published: April 2021

PurposeThe purpose of the paper is to describe and analyse the nature of accountability for human rights, as enacted by the Business & Human Rights Resource Centre (BHRRC), in this time of globalization and coronavirus disease 2019 (COVID-19). Design/methodology/approachThe authors focus on one case of alleged union-busting and unfair dismissal carried out under the cover of the COVID-19 pandemic. Tracing the action of that case, the authors show how the BHRRC provides a digital platform for dialogues of accountability. The authors use a Latourian theoretical perspective to guide the progress of the study’s analysis.FindingsThe authors find that the dialogues of accountability enacted on the BHRRC platform cannot be satisfactorily characterized in terms of an old politics of hegemony, counterhegemony and counter accounts. The authors find that the accountability enacted on the platform operates in three modes: in a political mode to support the formation of issues and publics and the embedding of norms; in an organizational mode to support the (re)organizing business corporations around scripts of respect for human rights; in a moral mode to keep scruples concerning means and ends and the pursuit of better outcomes, open.Originality/valueThe paper is novel, in that it engages with the part that accounting can play in politics conceived in Latourian terms; in its introduction, a notion of modes of accountability on the foundations of Latour’s exploration of modes of existence; in its challenge to the value of critical accounting conceived in terms of hegemony and counterhegemony.
Policy asymmetries and fiscal sustainability: evidence from Nigeria
Authors: Adeosun Opeoluwa Adeniyi , Ayodele Olumide Steven , Jongbo Olajide Clement 
Published: April 2021

PurposeThis study examines and compares different specifications of the fiscal policy rule in the fiscal sustainability analysis of Nigeria.Design/methodology/approachThis is methodologically achieved by estimating the baseline constant-parameter and Markov regime switching fiscal models. The asymmetric autoregressive distributed lag fiscal model is also employed to substantiate the differential responses of fiscal authorities to public debt.FindingsThe baseline constant-parameter fiscal model provides mixed results of sustainable and unsustainable fiscal policy. The inconclusiveness is adduced to instability in primary fiscal balance–public debt dynamics. This makes it necessary to capture regime switches in the fiscal policy rule. The Markov switching estimations show a protracted fiscal unsustainable regime that is inconsistent with the intertemporal budget constraint (IBC). The no-Ponzi game and debt stabilizing results of the Markov switching fiscal model further revealed that the transversality and debt stability conditions were not satisfied. Additional findings from the asymmetric autoregressive model estimation show that fiscal consolidation responses vary with contraction and expansion in output and spending, coupled with downturns and upturns in public debt dynamics in both the long and short run. These findings thus confirm the presence of asymmetries in the fiscal policy authorities' reactions to public debt. Further, additional evidences show the violation of the IBC which is exacerbated by the deleterious effect of the pro-cyclical fiscal policy response in boom on the improvement of the primary fiscal balance.Originality/valueThis study deviates from the extant literature by accommodating time variation, periodic switches and fiscal policy asymmetries in the fiscal sustainability analysis of Nigeria.
Some remarks on invariant lightlike submanifolds of indefinite Sasakian manifold
Authors: Ssekajja Samuel 
Published: April 2021

PurposeThe author considers an invariant lightlike submanifold M, whose transversal bundle tr(TM) is flat, in an indefinite Sasakian manifold M¯(c) of constant φ¯-sectional curvature c. Under some geometric conditions, the author demonstrates that c=1, that is, M¯ is a space of constant curvature 1. Moreover, M and any leaf M′ of its screen distribution S(TM) are, also, spaces of constant curvature 1.Design/methodology/approachThe author has employed the techniques developed by K. L. Duggal and A. Bejancu of reference number 7.FindingsThe author has discovered that any totally umbilic invariant ligtlike submanifold, whose transversal bundle is flat, in an indefinite Sasakian space form is, in fact, a space of constant curvature 1 (see Theorem 4.4).Originality/valueTo the best of the author’s findings, at the time of submission of this paper, the results reported are new and interesting as far as lightlike geometry is concerned.