bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegaloviral determinants of CD8+T cell programming and RhCMV/SIV vaccine efficacy
Authors: Malouli Daniel , Hansen Scott G. , Hancock Meaghan H. , Hughes Colette M. , Ford Julia C. , Gilbride Roxanne M. , Ventura Abigail B. , Morrow David , Randall Kurt T. , Taher Husam , Uebelhoer Luke S. , McArdle Matthew R. , Papen Courtney R. , Trethewy Renee Espinosa , Oswald Kelli , Shoemaker Rebecca , Berkemeier Brian , Bosche William J. , Hull Michael , Greene Justin M. , Axthelm Michael K. , Shao Jason , Edlefsen Paul T. , Grey Finn , Nelson Jay A. , Lifson Jeffrey D. , Streblow Daniel , Sacha Jonah B. , Früh Klaus , Picker Louis J. 
Published: October 2020

AbstractSimian immunodeficiency virus (SIV) insert-expressing, 68-1 Rhesus Cytomegalovirus (RhCMV/SIV) vectors elicit major histocompatibility complex (MHC)-E- and -II-restricted, SIV-specific CD8+T cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against SIV challenge in the rhesus monkeys (RMs) has not been characterized. We demonstrate that these unconventional responses resulted from a chance genetic rearrangement in 68-1 RhCMV that abrogated the function of eight distinct immunomodulatory gene products encoded in two RhCMV genomic regions (Rh157.5/.4 and Rh158-161). Differential repair of these genes with either RhCMV-derived or orthologous human CMV (HCMV)-derived sequences (UL128/130; UL146/147) leads to either of two distinct CD8+T cell response types – MHC-Ia-restricted-only, or a mix of MHC-II- and MHC-Ia-restricted CD8+T cells. Despite response magnitude and functional differentiation being similar to RhCMV 68-1, neither alternative response type mediated protection against SIV challenge. These findings implicate MHC-E-restricted CD8+T cell responses as mediators of anti-SIV efficacy and indicate that translation of RhCMV/SIV vector efficacy to humans will likely require deletion of all the genes that inhibit these responses from the HCMV/HIV vector.One-sentence summaryEight genes in two spatially distinct RhCMV gene regions control induction of unconventionally restricted CD8+T cell responses and the efficacy of RhCMV/SIV vaccine vectors against SIV challenge.
Impact of COVID-19 lockdown on psychosocial factors, health, and lifestyle in Scottish octogenarians: the Lothian Birth Cohort 1936 Study
Authors: Taylor Adele M. , Page Danielle , Okely Judith A. , Corley Janie , Welstead Miles , Skarabela Barbora , Redmond Paul , Russ Tom C. , Cox Simon R. 
Published: October 2020

ABSTRACTBackgroundLittle is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group.MethodsLothian Birth Cohort 1936 members, mean age 84 years (SD=0.3), responded to an online questionnaire in May 2020 (n=190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes.ResultsFour respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR=0.71, 95%CI 0.51– 0.98) and poorer self-rated general health (OR=0.62, 95%CI 0.42–0.92). Increased internet use associated with female sex (OR=2.32, 95%CI 1.12–4.86) and higher general cognitive ability (OR=1.53, 95%CI 1.03–2.33). Loneliness associated with living alone (OR=0.15, 95%CI 0.07–0.31) and greater anxiety symptoms (OR=1.76, 95%CI 0.45–1.24). COVID-19 related stress associated with lower emotional stability scores (OR=0.40, 95%CI 0.24–0.62). Decreased physical activity associated with less professional occupational class (OR=1.43, 95%CI 1.04–1.96), and lower general cognitive ability (OR=0.679, 95%CI 0.491–0.931).ConclusionsCharacteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes.
Selection for increased tibia length in mice alters skull shape through parallel changes in developmental mechanisms
Authors: Unger Colton M. , Devine Jay , Hallgrímsson Benedikt , Rolian Campbell 
Published: October 2020

AbstractBones in the vertebrate cranial base and limb skeleton grow by endochondral ossification, under the control of growth plates. Mechanisms of endochondral ossification are conserved across growth plates, which increases covariation in size and shape among bones, and in turn may lead to correlated changes in skeletal traits not under direct selection. We used micro-CT and geometric morphometrics to characterize shape changes in the cranium of the Longshanks mouse, which was selectively bred for longer tibiae. We show that Longshanks skulls became longer, flatter, and narrower in a stepwise process. Moreover, we show that these morphological changes likely resulted from developmental changes in the growth plates of the Longshanks cranial base, mirroring changes observed in its tibia. Thus, indirect and non-adaptive morphological changes can occur due to developmental overlap among distant skeletal elements, with important implications for interpreting the evolutionary history of vertebrate skeletal form.
HiCORE: Hi-C analysis for identification of core chromatin loops with higher resolution and reliability
Authors: Lee Hongwoo , Seo Pil Joon 
Published: October 2020

AbstractGenome-wide chromosome conformation capture (3C)-based high-throughput sequencing (Hi-C) has enabled identification of genome-wide chromatin loops. Because the Hi-C map with restriction fragment resolution is intrinsically associated with sparsity and stochastic noise, Hi-C data are usually binned at particular intervals; however, the binning method has limited reliability, especially at high resolution. Here, we describe a new method called HiCORE, which provides simple pipelines and algorithms to overcome the limitations of single-layered binning and predict core chromatin regions with 3D physical interactions. In this approach, multiple layers of binning with slightly shifted genome coverage are generated, and interacting bins at each layer are integrated to infer narrower regions of chromatin interactions. HiCORE predicts chromatin looping regions with higher resolution and contributes to the identification of the precise positions of potential genomic elements.Author SummaryThe Hi-C analysis has enabled to obtain information on 3D interaction of genomes. While various approaches have been developed for the identification of reliable chromatin loops, binning methods have been limitedly improved. We here developed HiCORE algorithm that generates multiple layers of bin-array and specifies core chromatin regions with 3D interactions. We validated our algorithm and provided advantages over conventional binning method. Overall, HiCORE facilitates to predict chromatin loops with higher resolution and reliability, which is particularly relevant in analysis of small genomes.
Inhibiting the mitochondrial pyruvate carrier does not ameliorate synucleinopathy in the absence of inflammation or metabolic deficits
Authors: Peelaerts Wouter , Bergkvist Liza , George Sonia , Johnson Michaela , Meyerdirk Lindsay , Ku Emily , Steiner Jennifer A. , Madaj Zachary , Ma Jiyan , Becker Katelyn , Nilsson K. Peter R. , Colca Jerry , Brundin Patrik 
Published: October 2020

AbstractEpidemiological studies suggest a link between type-2 diabetes and Parkinson’s disease (PD) risk. Treatment of type-2 diabetes with insulin sensitizing drugs lowers the risk of PD. We previously showed that the insulin sensitizing drug, MSDC-0160, ameliorates pathogenesis in some animal models of PD. MSDC-0160 reversibly binds the mitochondrial pyruvate carrier (MPC) protein complex, which has an anti-inflammatory effect and restores metabolic deficits. Since PD is characterized by the deposition of α-synuclein (αSyn), we hypothesized that inhibiting the MPC might directly inhibit αSyn aggregationin vivoin mammals. To answer if modulation of MPC can reduce the development of αSyn assemblies, and reduce neurodegeneration, we treated two chronic and progressive mouse models; a viral vector-based αSyn overexpressing model and a pre-formed fibril (PFF) αSyn seeding model with MSDC-0160. These two models present with distinct types of αSyn pathology but lack inflammatory or autophagy deficits. Contrary to our hypothesis, we found that a modulation of MPC in these models did not reduce the accumulation αSyn aggregates or mitigate neurotoxicity. Instead, MSDC-0160 changed the post-translational modification and aggregation features of the αSyn. These results are consistent with the lack of a direct effect on MPC modulation on synuclein clearance in these models.
Genome-wide association study reveals the genetic architecture of 27 yield-related traits in tomato
Authors: Ye Jie , Wang Xin , Wang Wenqian , Yu Huiyang , Ai Guo , Li Changxing , Sun Pengya , Wang Xianyu , Li Hanxia , Ouyang Bo , Zhang Junhong , Zhang Yuyang , Giovannoni James J. , Fei Zhangjun , Ye Zhibiao 
Published: October 2020

ABSTRACTTomato (Solanum lycopersicum) is a highly valuable vegetable crop and yield is one of the most important traits. Uncovering the genetic architecture of yield-related traits in tomato is critical for the management of vegetative and reproductive development, thereby enhancing yield. Here we perform a comprehensive genome-wide association study for 27 yield-related traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many reported and novel genes related to vegetative and reproductive development, were identified, and these loci explained an average of ∼8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection, especially during tomato improvement. Furthermore, a candidate gene,SlALMT15that encodes an aluminum-activated malate transporter, was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation through increasing photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.
Single-cell multimodal profiling of proteins and chromatin accessibility using PHAGE-ATAC
Authors: Fiskin Evgenij , Lareau Caleb A , Eraslan Gökcen , Ludwig Leif S , Regev Aviv 
Published: October 2020

AbstractMulti-modal measurements of single cell profiles are a powerful tool for characterizing cell states and regulatory mechanisms. While current methods allow profiling of RNA along with either chromatin or protein levels, connecting chromatin state to protein levels remains a barrier. Here, we developed PHAGE-ATAC, a method that uses engineered camelid single-domain antibody (‘nanobody’)-displaying phages for simultaneous single-cell measurement of surface proteins, chromatin accessibility profiles, and mtDNA-based clonal tracing through a massively parallel droplet-based assay of single-cell transposase-accessible chromatin with sequencing (ATAC-seq). We demonstrate PHAGE-ATAC for multimodal analysis in primary human immune cells and for sample multiplexing. Finally, we construct a synthetic high-complexity phage library for selection of novel antigen-specific nanobodies that bind cells of particular molecular profiles, opening a new avenue for protein detection, cell characterization and screening with single-cell genomics.
Endogenous Galectin-3 is Required for Skeletal Muscle Repair
Authors: Cerri Daniel Giuliano , Rodrigues Lilian Cataldi , Alves Vani Maria , Machado Juliano , Bastos Víctor Alexandre Félix , do Carmo Kettelhut Isis , Alberici Luciane Carla , Stowell Sean R. , Costa Maria Cristina R. , Cummings Richard D. , Dias-Baruffi Marcelo 
Published: October 2020

ABSTRACTSkeletal muscle has the intrinsic ability to self-repair through a multifactorial process, but many aspects of its cellular and molecular mechanisms are not fully understood. There is increasing evidence that some members of the mammalian β-galactoside-binding protein family (galectins) are involved in the muscular repair process (MRP), including galectin-3 (Gal-3). However, there are many questions about the role of this protein on muscle self-repair. Here, we demonstrate that endogenous Gal-3 is required for: i) muscle repairin vivousing a chloride-barium myolesion mouse model, and ii) mouse primary myoblasts myogenic programming. Injured muscle from Gal-3 knockout mice (GAL3KO) showed persistent inflammation associated with compromised muscle repair and the formation of fibrotic tissue on the lesion site. InGAL3KOmice, osteopontin expression remained high even after 7 and 14 days of the myolesion, while MyoD and myogenin had decreased their expression. InGAL3KOmouse primary myoblast cell culture, Pax7 detection seems to sustain even when cells are stimulated to differentiation and MyoD expression is drastically reduced. These findings suggest that the detection and temporal expression levels of these transcriptional factors appear to be altered in Gal-3-deficient myoblast cell culture compared to Wild Type (WT) cells. We observed Gal-3 expression in WT states, bothin vivoandin vitro, in sarcoplasm/cytoplasm and myonuclei; as differentiation proceeds, Gal-3 expression is drastically reduced, and its location is confined to the sarcolemma/plasma cell membrane. We also observed a change in the temporal-spatial profile of Gal-3 expression and muscle transcription factors levels during the myolesion. Overall, these results demonstrate that endogenous Gal-3 is required for the skeletal muscle repair process.
Phages weaponize their bacteria with biosynthetic gene clusters
Authors: Dragoš Anna , Andersen Aaron J.C. , Lozano-Andrade Carlos N. , Kempen Paul J. , Kovács Ákos T. , Strube Mikael Lenz 
Published: October 2020

ABSTRACTBacteria produce many different specialized metabolites, which are encoded by biosynthetic gene clusters (BGCs). Despite high industrial relevance owing to broad bioactive potential of these metabolites, their ecological roles remain largely unexplored. We analyze all available genomes for BGCs of phage origin. The BGCs predominantly reside within temperate phages infecting certain commensal and pathogenic bacteria. Nearly all phage BGCs encode bacteriocins, which appear to serve as a strong proxy for phage specificity. Using the gut-associated bacteriumBacillus subtilis, we demonstrate how a temperate phage equips its host with a functional BGC, providing it with a competitive fitness advantage over close relatives. Therefore, certain temperate phages use BGCs to weaponize their bacteria against close relatives, leading to evolutionary benefits from lysogeny to the infected host, and hence, to the phage itself. Our study is a large step towards understanding the natural role of specialized metabolites, as well as mutualistic phage-host relationships.
Advax adjuvant formulations promote protective immunity against aerosolMycobacterium tuberculosisin the absence of deleterious inflammation and reactogenicity
Authors: Quan Diana H. , Counoupas Claudio , Nagalingam Gayathri , Pinto Rachel , Petrovsky Nikolai , Britton Warwick J. , Triccas James A. 
Published: October 2020

AbstractThe development of safe and effective adjuvants is a critical goal of vaccine development programs. In this report, we defined the immunostimulatory profile and protective effect against aerosolMycobacterium tuberculosisinfection of vaccine formulations incorporating the semi-crystalline adjuvant δ-inulin (Advax). Advax formulated with CpG oligonucleotide and the QS-21 saponin (AdvaxCpQS) was the most effective combination, demonstrated by the capacity of CysVac2/AdvaxCpQSto significantly reduce the bacterial burden in the lungs ofM. tuberculosis-infected mice. CysVac2/AdvaxCpQSprotection was associated with rapid influx of neutrophils, macrophages and monocytes to the site of vaccination and the induction of antigen-specific IFN-γ+/IL-2+/TNF+polyfunctional CD4+T cells in the lung. When compared to the highly potent adjuvant combination of monophosphoryl lipid A and dimethyldioctadecylammonium bromide (MPL/DDA), AdvaxCpQSimparted a similar level of protective efficacy yet without the profound stimulation of inflammatory cytokines and vaccination site ulceration observed with MPL/DDA. Addition of DDA to CysVac2/ AdvaxCpQSfurther improved the protective effect of the vaccine, which correlated with increased polyfunctional CD4+T cells in the lung but with no increase in vaccine reactogenicity. The data demonstrate that Advax formulations can decouple protective tuberculosis immunity from reactogenicity, making them ideal candidates for human application.HighlightsAdvax adjuvant formulations improve pulmonary protection against aerosolMycobacterium tuberculosisinfectionDifferent combinations of adjuvant components markedly influence the level of protection observedProtection is associated with the rapid influx of myeloid cells to the site of vaccination and the induction of antigen-specific polyfunctional CD4+T cells in the lung.Advax formulations abrogate vaccine-site ulceration and inflammatory cytokine production
The history and evolution of the Denisovan-EPAS1haplotype in Tibetans
Authors: Zhang Xinjun , Witt Kelsey , Ko Amy , Yuan Kai , Xu Shuhua , Nielsen Rasmus , Huerta-Sanchez Emilia 
Published: October 2020

AbstractRecent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high altitude environments on the Tibetan Plateau. Specifically, theEPAS1gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here we leverage data fromEPAS1in 78 Tibetan individuals to interrogate which of these two introgression events introduced theEPAS1beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 43,000 (15,700–60,000) years ago, and selection started 12,000 (1,925-50,000) years ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.
Investigating autism associated genes inC. elegansreveals candidates with a role in social behaviour
Authors: Rawsthorne Helena , Calahorro Fernando , Holden-Dye Lindy , O’ Connor Vincent , Dillon James 
Published: October 2020

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours. Investigations are well served by experimental approaches that allow tractable investigation of the underpinning genetic basis of circuits that control behaviours that operate in the biological domains that are neuro-atypical in autism. The model organismC. elegansprovides an experimental platform to investigate the effect of genetic mutations on behavioural outputs including those that impact social biology. Here we use progeny-derived social cues that modulateC. elegansfood leaving to assay genetic determinants of social behaviour. We used the SAFRI Gene database to identifyC. elegansorthologues of human ASD associated genes. We identified a number of mutants that displayed selective deficits in response to progeny. The genetic determinants of this complex social behaviour highlight the important contribution of synaptopathy and implicates genes within cell signalling, epigenetics and phospholipid metabolism functional domains. The approach overlaps with a growing number of studies that investigate potential molecular determinants of autism inC. elegans. However, our use of a complex, sensory integrative, emergent behaviour provides routes to enrich new or underexplored biology with the identification of novel candidate genes with a definable role in social behaviour.
The role of innovation in the relationship between university–industry collaboration in R&D and ISO 9001
Authors: Aldabbas Hazem , Pinnington Ashly , Lahrech Abdelmounaim 
Published: October 2020

PurposeThis study aims to investigate the relationship between university–industry collaboration (U-I-C) in research and development (R&D) and quality management and explore how the relationship is mediated by innovation.Design/methodology/approachBased on panel data consisting of 109 countries spanning over a five year period (2013-2017) this study investigates, through structural equation modelling, how this relationship is mediated by innovation.FindingsThe main finding is that there are positive significant direct effects between U-I-C and innovation and between innovation and international organization for standardization (ISO) 9001. Furthermore, the strength and significance of these relations are highly affected by the classification of income in these countries, which ranges from high and upper-middle to lower-middle categories. This paper concludes that countries in the high-income category have higher achievement in U-I-C in R&D, innovation and ISO 9001 when compared to the upper and lower-middle-income categories.Originality/valueThis paper demonstrates in the empirical study the value of collaboration in R&D between government, industry and academia, as it can encourage scientific research and contribute to quality management and innovation. This research is one of the very few studies to assess the country’s income classification effect on U-I-C in R&D, innovation and ISO 9001. It is recommended that more research is conducted on how countries not ranked in the high-income category could benefit from U-I-C in R&D to enhance innovation and quality management.