bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constancy and Change in the 5’UTR of Yellow Fever Virus
Authors: Seligman Stephen J. 
Published: July 2020

AbstractThe nucleotide composition of the 5’UTR of the yellow fever virus (YFV) has been reported to be the most constant sequence in the viral genome, but a comprehensive analysis of this constancy has not been presented. The current report is an analysis of the 5’UTRs from 48 sequences deposited in GenBank representing the seven described genotypes, five in Africa and two in the Americas. The YFV 5’UTRs consist of 118-120 nucleotides, 92% (110/119) of which are constant in all sequences. The constancy is impressive and suggests that many participate in significant viral functions. Remarkably, analysis of the non-constant nucleotides revealed that in some instances the non-constant nucleotide changes persisted in one or a restricted number of related genotypes and were from sequences isolated over a considerable span of years. This constant feature of non-constant nucleotides is consistent with the concept that the changes were in response to different environmental features such as changes in mosquito hosts or animal reservoirs, particularly as a consequence of spread of YFV from Africa to the New World. Constancy of 5’UTR in general may be helpful in distinction of viral species. Lastly, the presence of sequences of constant nucleotides greater than 19 nucleotides suggests regions of the 5’UTR that may be exploited for use as non-codon RNA as treatment and diagnostic agents in a variety of viral diseases.ImportanceThe 5’UTR is arguably the most neglected portion of the viral genome. It is frequently incomplete in the sequences deposited as otherwise complete sequences in GenBank. The current report is an analysis of complete 5’UTR sequences selected from those deposited in GenBank and indicates that the 5’UTR is 92% conserved confirming that it is a highly conserved portion of the viral genome and suggesting that each conserved nucleotide may be functionally significant. Repeated occurrences of even non-constant nucleotides belong to a restricted number of genotypes raising the possibility that adaptation to new mosquito hosts and animal reservoirs such as those that accompanied spread of yellow fever virus from Africa to the Western Hemisphere are relevant. Knowledge of prolonged strings of invariable nucleotides in the 5’UTR has been used in designing a method for detecting YFV and may also be relevant for designing sequences for viral control of a variety of viruses.
A single-cell transcriptome atlas of the aging human and macaque retina
Authors: Yi Wenyang , Lu Yufeng , Zhong Suijuan , Zhang Mei , Sun Le , Dong Hao , Wang Mengdi , Wei Min , Xie Haohuan , Qu Hongqiang , Peng Rongmei , Hong Jing , Yao Ziqin , Tong Yunyun , Wang Wei , Ma Qiang , Liu Zeyuan , Ma Yuqian , Li Shouzhen , Yin Chonghai , Liu Jianwei , Ma Chao , Wang Xiaoqun , Wu Qian , Xue Tian 
Published: July 2020

AbstractThe human retina is a complex neural tissue that detects light and sends visual information to the brain. However, the molecular and cellular processes that underlie aging primate retina remain unclear. Here, we provide a comprehensive transcriptomic atlas based on 119,520 single cells of the foveal and peripheral retina of humans and macaques covering different ages. The molecular features of retinal cells differed between the two species, suggesting the distinct regional and species specializations of the human and macaque retinae. In addition, human retinal aging occurred in a region- and cell-type- specific manner. Aging of human retina exhibited a foveal to peripheral gradient.MYO9A−rods and a horizontal cell subtype were greatly reduced in aging retina, indicating their vulnerability to aging. Moreover, we generated a dataset showing the cell-type- and region- specific gene expression associated with 55 types of human retinal disease, which provides a foundation to understand the molecular and cellular mechanisms underlying human retinal diseases. Together, these datasets are valuable for understanding the molecular characteristics of primate retina, as well as the molecular regulation of aging progression and related diseases.
Effect of chlorination and pressure flushing of drippers fed by reclaimed wastewater on biofouling
Authors: Lequette Kévin , Ait-Mouheb Nassim , Adam Nicolas , Muffat-Jeandet Marine , Bru-Adan Valérie , Wéry Nathalie 
Published: July 2020

AbstractDripper clogging reduces the performance and service life of a drip irrigation system. The impact of chlorination (1.5 ppm of free chlorine during 1 h application) and pressure flushing (0.18 MPa) on the biofouling of non-pressure-compensating drippers fed by real reclaimed wastewater was studied at lab scale using Optical Coherence Tomography. The effect of these treatments on microbial composition (bacteria and eukaryotes) was also investigated by High-throughput DNA sequencing. Biofouling was mainly observed in inlet, outlet and return areas of the drippers. Chlorination limited biofilm development mainly in the mainstream of the milli-labyrinth channel. It was more efficient when combined with pressure flushing. Moreover, chlorination was more efficient in maintaining the water distribution uniformity. It reduced the bacterial concentration and the diversity of the dripper biofilms compared to the pressure flushing method. This method strongly modified the microbial communities, promoting chlorine-resistant bacteria such asComamonadaceaeorAzospira. Inversely, several bacterial groups were identified as sensitive to chlorination such as Chloroflexi and Planctomycetes. Nevertheless, one month after stopping the treatments the bacterial diversity re-increased and the chlorine-sensitive bacteria such as Chloroflexi phylum and the Saprospiraceae, Spirochaetaceae, Christensenellaceae and Hydrogenophilaceae families re-emerged with the growth of biofouling, highlighting the resilience of the bacteria from drippers. Based on PCoA analyses, the structure of the communities still clustered separately from never-chlorinated drippers, showing that the effect of chlorination was still present one month after stopping the treatment.HighlightsThe fouling of drippers is a bottleneck for drip irrigation using reclaimed wastewaterBiofouling was lowest when chlorination was combined with pressure flushingThe β-Proteobacteria and Firmicutes contain chlorine resistant bacteriaThe decrease of Chloroflexi by chlorination was transitoryThe bacterial community was resilient after the interruption of cleaning events
Trans-synaptic assemblies link synaptic vesicles and neuroreceptors
Authors: Martinez-Sanchez Antonio , Laugks Ulrike , Kochovski Zdravko , Papantoniou Christos , Baumeister Wolfgang , Lucic Vladan 
Published: July 2020

AbstractSynaptic transmission is characterized by fast, tightly coupled processes and complex signaling path-ways that require a distinctly non-random spatial organization of their components. Nanoscale organization of synaptic proteins at glutamatergic synapses was suggested to regulate synaptic plasticity, the process underlying learning and memory. Specifically, direct colocalization of pre- and postsynaptic proteins implicated that the alignment of neurotransmitter release sites with neurotransmitter receptors enables maximal synaptic response. However, direct visualization and the mechanistic understanding of this alignment is lacking. Here we used cryo-electron tomography to visualize synaptic complexes in their native environment with the full complement of their interacting partners, synaptic vesicles and plasma membranes on 2-4 nanometer scale. The application of our recent template-free detection and classification procedure showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors, and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in lipid membranes. The data presented support the hypothesis that synaptic function is carried by precisely organized trans-synaptic units. It complements superresolution findings and provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their function.
The impact of age on genetic risk for common diseases
Authors: Jiang Xilin , Holmes Chris , McVean Gil 
Published: July 2020

AbstractInherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Recent work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the relationship between genetic risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic risk. The predominant pattern shows genetic risk factors having the greatest impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants although the magnitude and form of the decrease varies among diseases. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.Author summaryThe genes we inherit from our parents influence our risk for almost all diseases, from cancer to severe infections. With the explosion of genomic technologies, we are now able to use an individual’s genome to make useful predictions about future disease risk. However, recent work has shown that the predictive value of genetic information varies by context, including age, sex and ethnicity. In this paper we introduce, validate and apply new statistical methods for investigating the relationship between age and genetic risk. These methods allow us to ask questions such as whether risk is constant over time, precisely how risk changes over time and whether all genetic risk factors have similar age profiles. By applying the methods to data from the UK Biobank, a prospective study of 500,000 people, we show that there is a tendency for genetic risk to decline with increasing age. We consider a series of possible explanations for the observation and conclude that there must be processes acting that we are currently unaware of, such as distinct phases of life in which genetic risk manifests itself, or interactions between genes and the environment.
Aspirin inhibition of prostaglandin synthesis impairs egg development across mosquito taxa
Authors: Al Baki Md. Abdullah , Ahmed Shabbir , Kwon Hyeogsun , Hall David R. , Smith Ryan C. , Kim Yonggyun 
Published: July 2020

AbstractSeveral endocrine signals are known to mediate mosquito egg development including insulin-like peptide, 20-hydroxyecdysone, and juvenile hormone. The objective of this study was to determine the effects of prostaglandin E2(PGE2) as an additional mediator of oogenesis in the mosquitoes,Aedes albopictusandAnopheles gambiae. The injection of aspirin (an inhibitor of cyclooxygenase) shortly after blood-feeding significantly inhibited egg development at choriogenesis in a dose-dependent manner inAe. albopictus. Moreover, oral administration of aspirin toAn. albopictusandAn. gambiaealso inhibited egg production. The aspirin treatment suppressed expression of the genes (Yellow-gandYellow-g2) associated with exochorion darkening and led to the production of a malformed egg shell inAe. albopictus. These inhibitory effects of aspirin on egg development were rescued by the addition of PGE2, confirming the specificity of aspirin in inhibiting prostaglandin production. To validate these results, we identified a putative PGE2receptor (Aa-PGE2R) inAe. albopictus. Aa-PGE2Rexpression was highly inducible in adult ovary after blood-feeding. RNA interference ofAa-PGE2Rexpression resulted in the significant suppression of choriogenesis similar to aspirin treatment, where the addition of PGE2toAa-PGE2R-silenced females failed to rescue egg production. Together, these results suggest that PG synthesis and signaling are required for egg development across diverse mosquito taxa.Author SummaryProgstaglandins (PGs) play crucial roles in mediating various physiological processes in insects. Aspirin (ASP) inhibits PG biosynthesis and has been used as an anti-inflammatory drug. ASP injection or feeding to mosquitoes ofAedes albopictusorAnopheles gambiaesignificantly inhibits egg production at chorion formation. This led to significant reduction in fecundity and egg hatchability. PG signal is interrupted by RNA interference (RNAi) of PGE2receptor. The RNAi treatment also gave a similar damage to females in egg production as seen in ASP treatment. Thus, PG signal is required for egg production of these mosquitoes.Data Availability StatementAll relevant data are within the manuscript and its Supporting Information file.
Water Resource Management: IWRM strategies for Improved Water Management. A Systematic Review of Case Studies of East, West and Southern Africa
Authors: Dirwai Tinashe Lindel , Kanda Edwin Kimuta , Senzanje Aidan , Busari Toyin Isiaka 
Published: July 2020

AbstractObjectiveThe analytical study systematically reviewed the evidence about the IWRM water strategy model. The study analysed the IWRM strategy advances and practical implications it had, since inception on effective water management in East, West and Southern Africa.MethodsThe study adopted the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) and the scoping literature review approach. The study searched selected databases for peer-reviewed articles, books, and grey literature. DistillerSR software was used for article screening. A constructionist thematic analysis was employed to extract recurring themes amongst the regions.ResultsThe systematic literature review detailed the adoption, policy revisions and growing/emerging policy trends and issues (or considerations) on IWRM in East, West and Southern Africa. Thematic analysis derived four cross-cutting themes that contributed to IWRM strategy implementation and adoption. The identified four themes were donor effect, water scarcity, transboundary water resources, and policy approach. The output further posited questions on the prospects, including whether IWRM has been a success or failure with the African water resource management fraternity.Graphical Abstract
Novel candidates of pathogenic variants of theBRCA1andBRCA2genes in a 3,552 Japanese whole-genome sequence dataset (3.5KJPNv2)
Authors: Tokunaga Hideki , Iida Keita , Hozawa Atsushi , Ogishima Soichi , Watanabe Yoh , Shigeta Shogo , Shimada Muneaki , Yamaguchi-Kabata Yumi , Tadaka Shu , Katsuoka Fumiki , Ito Shin , Kumada Kazuki , Hamanaka Yohei , Fuse Nobuo , Kinoshita Kengo , Yamamoto Masayuki , Yaegashi Nobuo , Yasuda Jun 
Published: July 2020

AbstractIdentification of pathogenic germline variants yet no clinical evidence inBRCAgenes has become important in patient care of hereditary breast and ovarian cancer syndrome (HBOC). Computational scoring and prospective cohort studies may help to identify such pathogenic variants. We annotated the variants in theBRCA1andBRCA2genes from a dataset of 3,552 whole-genome sequences obtained from members of the genome cohorts by Tohoku Medical Megabank Project (TMM) with the InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAF) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar are used for filtration criteria. Familial predispositions in cancers among the 35,000 TMM genome cohort participants are analyzed to verify the pathogenicity. Seven potentially pathogenic variants were newly identified. Carriers of these potential pathogenic variants and definite P and LP variants among participants of the TMM prospective cohort show a statistically significant preponderance in cancer onset in sisters in the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potential pathogenic variants inBRCAgenes for Japanese population. These results will be helpful to follow up the carriers of variants of uncertain significance in the HBOC genes.
The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing
Authors: Seidel Einat , Dassa Liat , Oiknine-Djian Esther , Wolf Dana G. , Le-Trilling Vu Thuy Khanh , Mandelboim Ofer 
Published: July 2020

AbstractNatural killer (NK) cells are innate immune lymphocytes capable of killing target cells without prior sensitization. NK cell activity is regulated by signals received from activating and inhibitory receptors. One pivotal activating NK receptor is NKG2D, which binds a family of eight ligands, including the major histocompatibility complex (MHC) class I-related chain A (MICA). Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunosuppressed patients and congenitally infected infants. HCMV encodes multiple antagonists of NK cell activation, including many mechanisms targeting MICA. However, only one of these mechanisms counters the most prevalent MICA allele, MICA*008. Here, we discover that a hitherto uncharacterized HCMV protein, UL147A, specifically targets MICA*008 to proteasomal degradation, thus hindering the elimination of HCMV-infected cells by NK cells. Mechanistic analyses disclose that the non-canonical GPI anchoring pathway of immature MICA*008 constitutes the determinant of UL147A specificity for this MICA allele. These findings advance our understanding of the complex and rapidly evolving HCMV immune evasion mechanisms, which may facilitate the development of antiviral drugs and vaccines.Author SummaryHuman cytomegalovirus (HCMV) is a common pathogen that usually causes asymptomatic infection in the immunocompetent population, but the immunosuppressed and fetuses infectedin uterosuffer mortality and disability due to HCMV disease. Current HCMV treatments are limited and no vaccine has been approved, despite significant efforts. HCMV encodes many genes of unknown function, and virus-host interactions are only partially understood. Here, we discovered that a hitherto uncharacterized HCMV protein, UL147A, downregulates the expression of an activating immune ligand allele named MICA*008, thus hindering the elimination of HCMV-infected cells. Elucidating HCMV immune evasion mechanisms could aid in the development of novel HCMV treatments and vaccines. Furthermore, MICA*008 is a highly prevalent allele implicated in cancer immune evasion, autoimmunity and graft rejection. In this work we have shown that UL147A interferes with MICA*008’s poorly understood, nonstandard maturation pathway. Study of UL147A may enable manipulation of its expression as a therapeutic measure against HCMV.
Genome-Scale CRISPR Screening reveals novel factors regulating Wnt-dependent regeneration of mouse gastric organoids
Authors: Murakami Kazuhiro , Terakado Yumi , Saito Kikue , Jomen Yoshie , Takeda Haruna , Oshima Masanobu , Barker Nick 
Published: July 2020

ABSTRACTAn ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding of the underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features ofin vivostem cell-driven epithelial regeneration, providing an excellentex vivoplatform for interrogation of key regulatory mechanisms. Here, we employed a Genome-Scale CRISPR Knock-Out (GeCKO) screening assay using mouse gastric epithelial organoids to identify novel modulators of Wnt-driven stem cell-dependent epithelial regeneration in the gastric mucosa. In addition to known Wnt pathway regulators such asApc, we found that knock-out (KO) ofAlk,Bclaf3orPrkrasupports the Wnt independent self-renewal of gastric epithelial cellsex vivo. In adult mice, expression of these factors is predominantly restricted to nonLgr5-expressing stem cell zones above the gland base, implicating a critical role for these factors in suppressing Wnt-dependent self-renewal of gastric epithelia. Furthermore, using comprehensive RNA-sequencing analysis, we found that these factors influence epithelial regeneration by regulating Wnt signalling, apoptosis and expression of Reg family genes which could contribute to the epithelial regeneration through JAK/STAT3 pathway.
Antiquity and fundamental processes of the antler cycle in Cervidae (Mammalia)
Authors: Rössner Gertrud E. , Costeur Loïc , Scheyer Torsten M. 
Published: July 2020

AbstractThe origins of the regenerative nature of antlers, being branched and deciduous apophyseal appendages of frontal bones of cervid artiodactyls, have long been associated with permanent evolutionary precursors. In this study, we provide novel insight into growth modes of evolutionary early antlers. We analysed a total of 34 early antlers affiliated to ten species, including the oldest known, dating from the early and middle Miocene (approx. 19 to 12 million years old) of Europe. Our findings provide empirical data from the fossil record to demonstrate that growth patterns and a regular cycle of necrosis, abscission and regeneration are consistent with data from modern antlers. The diverse histological analyses indicate that primary processes and mechanisms of the modern antler cycle were not gradually acquired during evolution, but were fundamental from the earliest record of antler evolution and, hence, explanations why deer shed antlers have to be rooted in basic histogenetic mechanisms.