bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies
Authors: Davies Alexander J , Lleixà Cinta , Siles Ana M. , Gourlay Dawn , Berridge Georgina , Dejnirattisai Wanwisa , Ramírez-Santana Carolina , Anaya Juan-Manuel , Falconar Andrew K. , Romero-Vivas Claudia M. , Osorio Lyda , Parra Beatriz , Screaton Gavin R. , Mongkolsapaya Juthathip , Fischer Roman , Pardo Carlos A. , Halstead Susan K. , Willison Hugh J. , Querol Luis , Rinaldi Simon 
Published: October 2021

ABSTRACTIntroductionRecent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurological side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4000 ZIKV cases. Whether the neurological symptoms of ZIKV infection are a consequence of autoimmunity or direct neurotoxicity is unclear.MethodsWe employed rat dorsal root ganglion (DRG) neurons, Schwann cells (SCs), and human stem cell-derived sensory neurons myelinated with rat SCs as cellular models to screen for IgG and IgM autoantibodies reactive to peripheral nerve in sera of ZIKV patients with and without GBS. In this study, 52 ZIKV-GBS patients were compared with 134 ZIKV-infected patients, and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array.ResultsOverall, IgG antibody reactivity to rat SCs (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequently, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to DRGs (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared to other controls, while IgM reactivity to co-cultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from one patient were confirmed to react with neurofascin-155 and 186. Serum from a ZIKV non-GBS patient displayed strong myelin-binding and anti-lipid antigen reaction characteristics. There was no significant association of ZIKV-GBS with any anti-glycolipid antibodies.ConclusionAutoantibodies in ZIKV associated GBS patients’ sera target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.
Social discrimination and stigma on the community of health professionals during the Covid-19 pandemic. An ethnographic approach
Authors: Argyriadis Alexandros , Patelarou Athina , Kitsona Vasiliki , Trivli Alexandra , Patelarou Evridiki , Argyriadi Agathi 
Published: October 2021

AbstractSevere Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) that caused the pandemic since March 2020, has affected among others, health professionals who work in covid-19 units by facing social discrimination. The aim of this study was to record the experiences of health professionals working in the first line of treatment of the pandemic, to analyse the effects of the pandemic on the interpersonal relationships of health professionals, and to ask about the stigma they faced during their work with people with covid-19.This is a qualitative study with an ethnographic approach based on 160 semi-structured interviews with health professionals living and working in the Epirus Region, Greece. For the data collection we used semi-structured interviews, discussions and participatory observation. Specifically, the interviews were conducted on health professionals and more specifically doctors, nurses, rescuers, physiotherapists and administrative staff, working in covid-19 units at the University General Hospital of Ioannina (Reference hospital for Ioannina, in Epirus), which assists in the treatment of patients with covid-19, and in the branch of the rescue department of Ioannina.The data were analysed in four thematic units based on their common characteristics: a) emotions and experiences of health professionals, b) interpersonal relations of health professionals, c) social exclusion and discrimination, and d) health professionals as patients. The results showed that the main emotions that health professionals experienced when they were moved to covid-19 clinics were fear, anxiety, distress, anger and insecurity. These feelings worsened when their family environment treated them with fear and hesitancy. Their social environment tended to avoid them, leading to a state of self-isolation. To conclude, health professionals faced discriminating behaviors and stigma both from their families and social environment, and from other health professionals. The government struggled to handle the situation in keeping a balance between both the security and well-being of health professionals as it was not prepared for a pandemic like this.
Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK
Authors: Waites William , Pearson Carl AB , Gaskell Katherine M , House Thomas , Pellis Lorenzo , Johnson Marina , Gould Victoria , Hunt Adam , Stone Neil RH , Kasstan Ben , Chantler Tracey , Lal Sham , Roberts Chrissy h. , Goldblatt David ,   CMMID COVID-19 Working Group, Marks Michael , Eggo Rosalind M 
Published: October 2021

AbstractSome social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.
Microglia-specific promoter activities of humanHexBgene
Authors: Shah Sahil , Wong Lilly M. , Ellis Kendra , Bondar Brittany , Saribas Sami , Ting Julia , Wei Zhengyu , Tang Yuyang , Wang Xianwei , Wang Hong , Ling Binhua , Margolis David M. , Garcia J. Victor , Hu Wenhui , Jiang Guochun 
Published: October 2021

AbstractAdeno-associated virus (AAV)-mediated genetic targeting of microglia remains challenging. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of theHexBgene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5’ untranslated region (−97 bp related to the first ATG) in driving transcriptional activity of the mouseHexBgene. The native promoter region of mouse, human and monkeyHexBlocated at -135, -134 and -170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but had no activities in primary astrocytes. In addition, we identified a 135 bp promoter ofCD68gene was also highly active in microglia but not in astrocytes. Considering thatHexBis specifically expressed in microglia, not in monocytes/macrophages or other neuronal cells, these data suggest that the newly characterized 134 bp microglia-specificHexBpromoter can be an ideal candidate for microglia-targeting AAV gene therapy, which could be developed for HIV eradication in the brain wherein microglia harbor the main HIV reservoirs in the CNS.SummaryIt is hard to overstate the importance of gene therapy that can remove viral genes from human cells. A cure for HIV would mean a lifetime free of treatment for patients who now must maintain a strict regimen of ART indefinitely. In order to develop a cure using AAV delivery, payload DNA must meet the AAV vector size limitations, and the payload genes must be expressed appropriately. Previous studies have identified microglia-specificHexBgene that shows stable expression during neural homeostasis and pathogenesis. Our study identified the essentialHexBgene promoter (134 bp) as a strong candidate for AAV gene therapy to specifically target the brain microglia, the main cellular reservoirs of HIV in the central nervous system. Our studies continue to move us closer to identifying target-specific gene therapy for NeuroAIDS.
Alu-mediated weak CEBPA binding and slow B cell transdifferentiation in human
Authors: Nurtdinov Ramil , Sanz María , Abad Amaya , Esteban Alexandre , Ullrich Sebastian , Arnan Carme , Johnson Rory , Pérez-Lluch Sílvia , Guigó Roderic 
Published: October 2021

AbstractMany developmental and differentiation processes take substantially longer in human than in mouse. To investigate the molecular mechanisms underlying this phenomenon, here we have specifically focused on the transdifferentiation from B cells to macrophages. The process is triggered by exactly the same molecular mechanism -- the induction by the transcription factor (TF) CEBPA -- but takes three days in mouse and seven in human (1, 2). In mouse, the speed of this process is known to be associated with Myc expression (3). We found that in this species, CEBPA binds strongly to the Myc promoter, efficiently down-regulating Myc. In human, in contrast, CEBPA does not bind this promoter, and MYC is indirectly and more slowly down-regulated. Attenuation of CEBPA binding is not specific to the MYC promoter, but a general trait of the human genome across multiple biological conditions. We traced back weak CEBPA binding to the primate-specific Alu repeat expansion. Many Alu repeats carry strong CEBPA binding motifs, which sequester CEBPA, and attenuate CEBPA binding genome-wide. We observed similar CEBPA and MYC dynamics in natural processes regulated by CEBPA, suggesting that CEBPA attenuation could underlie the longer duration in human processes controlled by this factor. Our work highlights the highly complex mode in which biological information is encoded in genome sequences, evolutionarily connecting, in an unexpected way, lineage-specific transposable element expansions to species-specific changes in developmental tempos.
Shift-inducible [transgenerational] increase in recombination rate as an evolving strategy in a periodic environment: a numerical model
Authors: Rybnikov Sviatoslav , Hübner Sariel , Korol Abraham B. 
Published: October 2021

AbstractNumerous empirical studies have witnessed a plastic increase in meiotic recombination rate in organisms experiencing physiological stress due to unfavourable environmental conditions. Yet, it is not clear enough which characteristics of an ecological factor (intensity, duration, variability, etc.) make it stressogenic and therefore recombinogenic for an organism. Several previous theoretical models proceeded from the assumption that organisms increase their recombination rate when the environment becomes more severe, and demonstrated the evolutionary advantage of such recombination strategy. Here we explore another stress-associated recombination strategy, implying a reversible increase in recombination rate each time when the environment alternates. We allow such plastic changes in the organisms, grown in an environment different from that of their parents, and, optionally, also in their offspring. We show that such shift-inducible recombination is always favoured over intermediate constant optimal recombination. Besides, it sometimes outcompetes also zero and free optimal constant recombination, therefore making selection on recombination less polarized. Shift-inducible strategies with a longer, transgenerational plastic effect, are favoured under slightly stronger selection and longer period. These results hold for both panmixia and partial selfing, although selfing makes the dynamics of recombination modifier alleles faster. Our results suggest that epigenetic factors, presumably underlying the environmental plasticity of recombination, may play an important evolutionary role.
Maternal Ezh1/2 deficiency in oocyte delays H3K27me2/3 restoration and impairs epiblast development responsible for embryonic sub-lethality in mouse
Authors: Zhao Yinan , Zhang Dan , Liu Mengying , Tian Yingpu , Lu Jinhua , Gao Shaorong , Wang Haibin , Lu Zhongxian 
Published: October 2021

AbstractMammalian embryonic development is a complex process regulated by various epigenetic modifications. Recently, maternal histone H3 methylations were found to be inherited and reprogrammed in early embryos to regulate embryonic development. The enhancer of zest homolog 1 and 2 (Ezh1 and Ezh2) belong to the core components of Polycomb repressive complex 2 (PRC2) and are the histone methyltransferase of histone 3 lysine 27 (H3K27). How maternal Ezh1 and Ezh2 function on H3K27 methylation in in vivo preimplantation embryos and embryonic development are not clear. Here, we deleted Ezh1 or/and Ezh2 in growing oocytes using gene knockout mouse models, and found that H3K27me3 in oocytes was disappeared by loss of Ezh2 alone while H3K27me2 was absent upon deletion of both Ezh1 and Ezh2. The effects of Ezh1/2 were inherited in maternal knockout zygotes and early embryos, in which restoration of H3K27me3 was delayed until late blastocyte by loss of Ezh2 alone and H3K27me2 was reestablished until morulae by deletion of Ezh1 and Ezh2. However, the ablation of both Ezh1 and Ezh2, but not single Ezh1 or Ezh2, led to significantly decreased litter size due to growth retardation during post-implantation. Furthermore, maternal Ezh1/2 deficiency caused compromised H3K27me3 and pluripotent epiblast cells in late blastocyst, followed by defective development of epiblast. These results demonstrate that in oocytes, Ezh2 is indispensable for H3K27me3 while Ezh1 complements Ezh2 in H3K27me2. Also, maternal Ezh1/2-H3K27 methylation is inherited in descendant embryos and has a critical effect on fetus and placenta development. Thus, this work sheds light on maternal epigenetic modifications during embryonic development.
Reduced myofibroblast transdifferentiation and fibrotic scarring in ischemic stroke after imatinib treatment
Authors: Zeitelhofer M. , Stefanitsch C. , Protzmann J. , Torrente D. , Adzemovic M.Z. , Lewandowski S.A. , Muhl L. , Eriksson U. , Nilsson I. , Su EJ. , Lawrence D. A. , Fredriksson L. 
Published: October 2021

AbstractThe tyrosine kinase inhibitor imatinib has been reported to improve outcome in patients following ischemic stroke but the exact mechanism remains elusive. Here, utilizing a photothrombotic murine model of middle cerebral artery occlusion (MCAO), we show that imatinib-mediated inhibition of stroke-induced blood-brain barrier (BBB) dysfunction coincided with decreased expression of genes associated with inflammation and fibrosis in the cerebrovasculature. We found that imatinib effectively dampened stroke-induced reactive gliosis and myofibroblast transdifferentiation, whilst having very limited effect on the rest of the glia scar and on peripheral leukocyte infiltration. Further, our data suggest that consolidation of the PDGFRα+ portion of the fibrotic scar in imatinib-treated mice contributes to the improvement in functional outcome compared to the vehicle controls, where the PDGFRα+ scar is expanding. Comparison with human stroke transcriptome databases revealed significant overlap with imatinib-regulated genes, suggesting imatinib may modulate reactive gliosis and fibrotic scarring also in human stroke.
Coevolution of relative brain size and life expectancy in parrots
Authors: Smeele Simeon Q. , Conde Dalia A. , Baudisch Annette , Bruslund Simon , Iwaniuk Andrew , Staerk Johanna , Wright Timothy F. , Young Anna M. , McElreath Mary Brooke , Aplin Lucy 
Published: October 2021

AbstractPrevious studies have demonstrated a correlation between longevity and brain size in a variety of taxa. Little research has been devoted to understanding this link in parrots; yet parrots are well-known for both their exceptionally long lives and cognitive complexity. We employed a large-scale comparative analysis that investigated the influence of brain size and life history variables on longevity in parrots. Specifically, we addressed two hypotheses for evolutionary drivers of longevity: theCognitive Buffer Hypothesis, which proposes that increased cognitive abilities enable longer life spans, and theExpensive Brain Hypothesis, which holds that increases in life span are caused by prolonged developmental time of, and increased parental investment in, large brained offspring. We estimated life expectancy from detailed zoo records for 133,818 individuals across 244 parrot species. Using a principled Bayesian approach that addresses data uncertainty and imputation of missing values, we found a consistent correlation between relative brain size and life expectancy in parrots. This correlation was best explained by a direct effect of relative brain size. Notably, we found no effects of developmental time, clutch size, or age at first reproduction. Our results suggest that selection for enhanced cognitive abilities in parrots have in turn promoted longer lifespans.
Repression of CENP-A assembly in metaphase requires HJURP phosphorylation and inhibition by M18BP1
Authors: Servin Julio C. Flores , Straight Aaron F. 
Published: October 2021

ABSTRACTCentromeres are the foundation for mitotic kinetochore assembly and thus are essential for chromosome segregation. Centromeres are epigenetically defined by nucleosomes containing the histone H3 variant CENP-A. CENP-A nucleosome assembly is uncoupled from replication and occurs in G1 but how cells control this timing is incompletely understood. The formation of CENP-A nucleosomes in vertebrates requires CENP-C and the Mis18 complex which recruit the CENP-A chaperone HJURP to centromeres. Using a cell-free system for centromere assembly in X. laevis egg extracts, we discover two activities that inhibit CENP-A assembly in metaphase. HJURP phosphorylation prevents the interaction between HJURP and CENP-C in metaphase, blocking the delivery of soluble CENP-A to centromeres. Non-phosphorylatable mutants of HJURP constitutively bind CENP-C in metaphase but are not sufficient for new CENP-A assembly. We find that the M18BP1.S subunit of the Mis18 complex also binds to CENP-C to competitively inhibit HJURP’s access to centromeres. Removal of these two inhibitory activities causes CENP-A assembly in metaphase.SUMMARYVertebrate CENP-A assembly is normally restricted to G1 phase. Two inhibitory activities, phosphorylation of HJURP and competitive binding of M18BP1.S to CENP-C, block HJURP’s access to the metaphase centromere. Removal of these inhibitory activities causes CENP-A assembly in metaphase.
Daily feeding rhythm linked to microbiome composition in two zooplankton species
Authors: Pfenning-Butterworth Alaina , Cooper Reilly O. , Cressler Clayton E. 
Published: October 2021

AbstractHost-associated microbial communities are impacted by external and within-host factors, i.e., diet and feeding behavior. For organisms known to have a circadian rhythm in feeding behavior, microbiome composition is likely impacted by the different rates of microbe introduction and removal across a daily cycle, in addition to any diet-induced changes in microbial interactions. Here, we measured feeding behavior and used 16S rRNA sequencing to compare the microbial community across a diel cycle in two distantly related species ofDaphnia,that differ in their life history traits, to assess how daily feeding patterns impact microbiome composition. We find thatDaphniaspecies reared under similar laboratory conditions have significantly different microbial communities. Additionally, we reveal thatDaphniahave daily differences in their microbial composition that correspond with feeding behavior, such that there is greater microbiome diversity at night during the host's active feeding phase. These results highlight that zooplankton microbiomes are relatively distinct and are likely influenced by host phylogeny.
Divergent evolutionary trajectories of bryophytes and tracheophytes from a complex common ancestor of land plants
Authors: Harris Brogan J. , Clark James W. , Schrempf Dominik , Szöllősi Gergely J. , Donoghue Philip C.J. , Hetherington Alistair M. , Williams Tom A. 
Published: October 2021

AbstractThe origin of plants and their colonization of land resulted in the transformation of the terrestrial environment. Here we investigate the evolution of the land plants (embryophytes) and their two main lineages, the tracheophytes (vascular plants) and bryophytes (non-vascular plants). We used new fossil calibrations, relative lineage dating implied by horizontal gene transfer, and new phylogenomic methods for mapping gene family origins. Distinct rooting strategies resolve tracheophytes and bryophytes as monophyletic sister groups that diverged during the Cambrian, 515-494 Ma. The embryophyte stem is characterised by a burst of gene innovation, while bryophytes subsequently experienced a no less dramatic episode of reductive genome evolution in which they lost genes associated with the elaboration of vasculature and the stomatal complex. Overall, our analyses confirm that extant tracheophytes and bryophytes are both highly derived; as a result, understanding the origin of land plants requires tracing character evolution across the diversity of modern lineages.
Sequencing Micronuclei Reveals the Landscape of Chromosomal Instability
Authors: Pereira Catalina , Rebelo Ana Rita , Massey Dashiell J. , Schimenti John C. , Weiss Robert S. , Koren Amnon 
Published: October 2021

AbstractGenome instability (GIN) is a main contributing factor to congenital and somatic diseases, but its sporadic occurrence in individual cell cycles makes it difficult to study mechanistically. One profound manifestation of GIN is the formation of micronuclei (MN), the engulfment of chromosomes or chromosome fragments in their own nuclear structures separate from the main nucleus. Here, we developed MN-seq, an approach for sequencing the DNA contained within micronuclei. We applied MN-seq to mice with mutations in Mcm4 and Rad9a, which disrupt DNA replication, repair, and damage responses. Data analysis and simulations show that centromere presence, fragment length, and a heterogenous landscape of chromosomal fragility all contribute to the patterns of DNA present within MN. In particular, we show that long genes, but also gene-poor regions, are associated with chromosome breaks that lead to the enrichment of particular genomic sequences in MN, in a genetic background-specific manner. Finally, we introduce single-cell micronucleus sequencing (scMN-seq), an approach to sequence the DNA present in MN of individual cells. Together, sequencing micronuclei provides a systematic approach for studying GIN and reveals novel molecular associations with chromosome breakage and segregation.