bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of early insect herbivory on the invasive oak lace bug (Corythucha arcuataSay, 1832) in different oak species
Authors: Valdés-Correcher Elena , de Groot Maarten , Schillé Laura , Stemmelen Alex , Mellerin Yannick , Bonnard Olivier , Castagneyrol Bastien 
Published: December 2022

AbstractInsect herbivores co-occurring on the same host plant interact in various ways. In particular, early-season insect herbivory triggers a wide range of plant responses that can determine the performance of herbivores colonizing the plant later in the course of the season. But the strength and direction of such effects are debated, and virtually unknown in the case of novel interactions involving exotic insects in their introduction range. We conducted an observational field study in SW France, a region recently invaded by the Oak Lace Bug (OLB,Corythucha arcuataSay). We measured early chewing damage and subsequent OLB damage in four oak species (Quercus robur, Q. pubescens, Q. cerrisandQ. ilex). We set up a complementary non-choice experiment in the laboratory, feeding OLB with leaves with or without prior herbivory. The four oak species differed in their sensitivity to OLB damage,Q. ilexbeing broadly resistant. Prior herbivory promoted OLB damage in the laboratory experiment, but not in the field. However, prior herbivory did not alter the rank of oak resistance to the OLB. Our results suggest possible synergistic effects between spring defoliators and the OLB. This study brings insight into herbivore-herbivore interactions and their possible implications for forest management.
Spontaneous body wall contractions stabilize the fluid microenvironment that shapes host-microbe associations
Authors: Nawroth JC , Giez C , Klimovich A , Kanso E , Bosch TCG 
Published: December 2022

AbstractThe freshwater polyp Hydra is a popular biological model system; however, we still do not understand one of its most salient behaviours, the generation of spontaneous body wall contractions. Here, by applying experimental fluid dynamics analysis and mathematical modelling, we provide functional evidence that spontaneous contractions of body walls enhance the transport of chemical compounds from and to the tissue surface where symbiotic bacteria reside. Experimentally, a reduction in the frequency of spontaneous body wall contractions is associated with a changed composition of the colonizing microbiota. Together, our findings suggest that spontaneous body wall contractions create an important fluid transport mechanism that (1) may shape and stabilize specific host-microbe associations and (2) create fluid microhabitats that may modulate the spatial distribution of the colonizing microbes. This mechanism may be more broadly applicable to animal-microbe interactions since research has shown that rhythmic spontaneous contractions in the gastrointestinal tracts are essential for maintaining normal microbiota.
The host phylogeny determines viral infectivity and replication acrossStaphylococcushost species
Authors: Walsh Sarah K , Imrie Ryan M , Matuszewska Marta , Paterson Gavin K , Weinert Lucy A , Hadfield Jarrod D , Buckling Angus , Longdon Ben 
Published: December 2022

AbstractGenetic similarity between eukaryotic host species is an important determinant of the outcome of virus host shifts, where a pathogen infects a novel host species. However, it is less clear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Understanding the patterns and determinants of cross-species transmissions may provide insights into the processes underlying pathogen emergence. Here, we measure the susceptibility of 64 strains ofStaphylococcusbacteria (48 strains ofS. aureusand 16 non-aureusspecies) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods – plaque assays, optical density (OD) assays, and quantitative (q)PCR – we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of onlyS. aureusstrains and models with a single representative from eachStaphylococcusspecies, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using a binary measure of plaque assay, OD, and qPCR, but not between the continuous component of plaque assay and any other method, suggesting that plaque assays alone may be inadequate to assess host range. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts.
Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response
Authors: Ramu Avinash , Cohen Barak 
Published: December 2022

AbstractStochastic differences among clonal cells can initiate cell fate decisions in development or cause cell-to-cell differences in the responses to drugs or extracellular ligands. We hypothesize that some of this phenotypic variability is caused by stochastic fluctuations in the activities of transcription factors. We tested this hypothesis in NIH3T3-CG cells using the response to Hedgehog signaling as a model cellular response. Here we present evidence for the existence of distinct fast and slow responding substates of NIH3T3-CG cells. These two substates have distinct expression profiles, and fluctuations in the activity of thePrrx1transcription factor (TF) underlie some of the differences in expression and responsiveness between fast and slow cells. We speculate that similar variability in other TFs may underlie other phenotypic differences among genetically identical cells.
Internal Normal Mode Analysis applied to RNA flexibility and conformational changes
Authors: Sabei Afra , Caldas Baia Talissa Gabriele , Saffar Raphaël , Martin Juliette , Frezza Elisa 
Published: December 2022

AbstractWe investigated the capability of internal normal modes to reproduce RNA dynamics and predict observed RNA conformational changes, and, notably, those induced by the formation of RNA-protein and RNA-ligand complexes. Here, we extended our iNMA approach developed for proteins to study RNA molecules using a simplified representation of RNA structure and its potential energy. Three datasets were also created to investigate different aspects. Despite all the approximations, our study shows that iNMA is a suitable method to take into account RNA flexibility and describe its conformational changes opening the route to its applicability in any integrative approach where these properties are crucial.
Pilot Study Demonstrates Benefits of Nursing Home Air Purification on COVID-19 Outcomes
Authors: Jutkowitz Eric , Shewmaker Peter , Reddy Ann , Braun Joseph M. , Baier Rosa R. 
Published: December 2022

AbstractImproving indoor air quality is one potential strategy to reduce the transmission of SARS-CoV-2 in any setting, including nursing homes, where staff and residents have been disproportionately and negatively affected by the COVID-19 pandemic. We used an interrupted time series design to compare trends in weekly COVID-19 cases and deaths before and after installation of ultraviolet air purification in 84 nursing homes in Florida, Georgia, North Carolina, and South Carolina from September 31, 2020 to December 27, 2020. Compared to pre-installation, weekly COVID-19 cases per 1,000 residents (−1.69, 95%CI: -4.32, 0.95) and the weekly probability of reporting any COVID-19 case (−0.02, 95%CI: -0.04, 0.00) declined in the post-installation period. We did not find any difference pre- and post-installation in COVID-19-related mortality (0.00 95%CI: -0.01, 0.02). Our findings from this small number of nursing homes in the southern US demonstrate the potential benefits of air purification in nursing homes on COVID-19 outcomes. We recommend a stronger experimental design to estimate the causal effect of installing air purification devices like this one on improving COVID-19 outcomes in nursing homes.Practical ImplicationsImproving indoor air quality is one potential strategy to reduce the burden of COVID-19 in nursing homes and nursing homes are eligible to receive Civil Monetary Penalty funding for purchases that improve air quality. Intervening on air quality may have a wide impact without placing significant burden on individuals to modify their behavior. In this pilot evaluation, we found that installing ultraviolet air purification may be an effective strategy to reduce COVID-19 cases in nursing homes. We recommend a stronger experimental design to determine the causal effect of indoor air interventions, such as air purification, on COVID-19 in this setting.
Potent Immunogenicity and Broad-Spectrum Protection Potential of Microneedle Array Patch-Based COVID-19 DNA Vaccine Candidates Encoding Dimeric RBD Chimera of SARS-CoV and SARS-CoV-2 Variants
Authors: Fan Feng , Zhang Xin , Zhang Zhiyu , Ding Yuan , Wang Limei , Xu Xin , Pan Yaying , Gong Fang-Yuan , Jiang Lin , Kang Lingyu , Kou Zhihua , Zhao Gan , Wang Bin , Gao Xiao-Ming 
Published: December 2022

ABSTRACTBreakthrough infections by SARS-CoV-2 variants pose a global challenge to pandemic control, and the development of more effective vaccines of broadspectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding heterodimeric receptor-binding domain (RBD) chimera of SARS-CoV and SARS-CoV-2 Omicron BA.1 (RBDSARS/BA1), SARS-CoV and SARS-CoV-2 Beta (RBDSARS/Beta), or Omicron BA.1 and Beta (RBDBA1/Beta) in secreted form. When i.m. injected in mice, RBDSARS/BA1and RBDSARS/Betaencoding plasmids (pAD1002 and pAD131, respectively) were by far more immunogenic than RBDBA1/Betaplasmid (pAD1003). Dissolvable microneedle array patches (MAP) laden with these DNA plasmids were fabricated. All 3 resulting MAP-based vaccine candidates, namely MAP-1002, MAP1003 and MAP-131, were comparable to i.m. inoculated plasmids with electroporation assistance in eliciting strong and durable IgG responses in BALB/c and C57BL/6 mice as well as rabbits, while MAP-1002 was comparatively the most immunogenic. More importantly, MAP-1002 significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-γ+T cells. Moreover, MAP-1002 antisera effectively neutralized pseudoviruses displaying spike proteins of SARS-CoV, prototype SARS-CoV-2 or Beta, Delta, Omicron BA1, BA2 and BA4/5 variants. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.
Assembly of 43 diverse human Y chromosomes reveals extensive complexity and variation
Authors: Hallast Pille , Ebert Peter , Loftus Mark , Yilmaz Feyza , Audano Peter A. , Logsdon Glennis A. , Bonder Marc Jan , Zhou Weichen , Höps Wolfram , Kim Kwondo , Li Chong , Hoyt Savannah J. , Dishuck Philip C. , Porubsky David , Tsetsos Fotios , Kwon Jee Young , Zhu Qihui , Munson Katherine M. , Hasenfeld Patrick , Harvey William T. , Lewis Alexandra P. , Kordosky Jennifer , Hoekzema Kendra ,   Human Genome Structural Variation Consortium (HGSVC), O’Neill Rachel J. , Korbel Jan O. , Tyler-Smith Chris , Eichler Evan E. , Shi Xinghua , Beck Christine R. , Marschall Tobias , Konkel Miriam K. , Lee Charles 
Published: December 2022

AbstractThe prevalence of highly repetitive sequences within the human Y chromosome has led to its incomplete assembly and systematic omission from genomic analyses. Here, we present long-readde novoassemblies of 43 diverse Y chromosomes spanning 180,000 years of human evolution, including two from deep-rooted African Y lineages, and report remarkable complexity and diversity in chromosome size and structure, in contrast with its low level of base substitution variation. The size of the Y chromosome assemblies varies extensively from 45.2 to 84.9 Mbp and include, on average, 81 kbp of novel sequence per Y chromosome. Half of the male-specific euchromatic region is subject to large inversions with a >2-fold higher recurrence rate compared to inversions in the rest of the human genome. Ampliconic sequences associated with these inversions further show differing mutation rates that are sequence context-dependent and some ampliconic genes show evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, the Yq12, is composed of alternating arrays ofDYZ1andDYZ2repeat units that show extensive variation in the number, size and distribution of these arrays, but retain a 1:1 copy number ratio of the monomer repeats, consistent with the notion that functional or evolutionary forces are acting on this chromosomal region. Finally, our data suggests that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kbp distal to the currently established boundary. The availability of sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of specific traits with Y-chromosomal variants and garnering novel insights into the evolution and function of complex regions of the human genome.
Tail-tape-fused virion and non-virion RNA polymerases of a thermophilic virus with an extremely long tail
Authors: Chaban Anastasiia , Minakhin Leonid , Goldobina Ekaterina , Bae Brain , Hao Yue , Borukhov Sergei , Putzeys Leena , Boon Maarten , Lavigne Rob , Makarova Kira S. , Koonin Eugene V. , Nair Satish K. , Tagami Shunsuke , Severinov Konstantin , Sokolova Maria L. 
Published: December 2022

AbstractThermus thermophilusbacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP)1that defines the length of its extraordinarily long 800 nm tail2,3. We found that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular and viral ‘two-barrel’ RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We determined the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab claw-like architecture similar to previously reported two-barrel RNAPs. The virion RNAP adopts a unique flat structure without a clamp, which likely reflects the requirement for its extrusion through the narrow channel in the phage tail for delivery into the cell. Structure and sequence comparisons of the P23-45 RNAPs with other phage and cellular RNAPs suggest that, despite the extensive functional differences, the two P23-45 RNAPs originate from an ancient gene duplication in an ancestral phage. Our findings demonstrate remarkable adaptability of two-barrel RNAPs that can be attained within a single virus species.
Evidence for HARKing in mouse behavioural tests of anxiety
Authors: Rosso Marianna , Herrera Adrian , Würbel Hanno , Voelkl Bernhard 
Published: December 2022

AbstractAnxiety disorders are among the most common mental health conditions needing new and better treatments. Research and development of anxiolytic drugs using animal models heavily rely on behavioural tests, most of which measure anxiolytic effects by increased exploratory activity in potentially threatening environments. However, interpretation of such tests is ambiguous because reduced exploratory activity can reflect either anxiety or sedation by the compound. Based on a systematic review of the sensitivity of mouse behavioural tests of anxiety to anxiolytic drugs, we analysed outcomes of 206 studies testing the effect of diazepam in either the open-field test or the hole-board test, as outcomes of these tests showed substantial variation in both direction and strength of the drug effect. Surprisingly, we found that both the rationale given for using the test, whether to detect anxiolytic or sedative effects, and the predicted effect of diazepam, anxiolytic or sedative, strongly depended on the reported test results. The most likely explanation for such strong dependency is post-hoc reasoning, also called hypothesizing after the results are known (HARKing). HARKing can invalidate study outcomes and hampers evidence synthesis by inflating effect sizes. It may also lead researchers into blind alleys, put patients in clinical trials at risk, and waste animals, time, and resources for inconclusive research.
Joint Multi-Ancestry and Admixed GWAS Reveals the Complex Genetics behind Human Cranial Vault Shape
Authors: Goovaerts Seppe , Hoskens Hanne , Eller Ryan J , Herrick Noah , Musolf Anthony M , Justice Cristina M , Yuan Meng , Naqvi Sahin , Lee Myoung Keun , Vandermeulen Dirk , Szabo-Rogers Heather L , Romitti Paul A , Boyadjiev Simeon A , Marazita Mary L , Shaffer John R , Shriver Mark D , Wysocka Joanna , Walsh Susan , Weinberg Seth M , Claes Peter 
Published: December 2022

AbstractThe cranial vault – the portion of the skull surrounding the brain and cerebellum – is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conducted a joint multi-ancestry and admixed multivariate GWAS on 3D cranial vault shape extracted from magnetic resonance images of 6,772 children from the ABCD study cohort, identifying 30 genome-wide significant genetic loci and replicating 20 of these signals in 16,947 additional individuals of the UK Biobank. This joint multi-ancestry GWAS was enriched for genetic components of cranial vault shape shared across ancestral groups and yielded a greater discovery than a European-only GWAS. We present supporting evidence for parietal versus frontal bone localization for several of the identified genes based on expression patterns in E15.5 mice. Collectively, our GWAS loci were enriched for processes related to skeletal development and showed elevated activity in cranial neural crest cells, suggesting a role during early craniofacial development. Among the identified genes, wereRUNX2and several of its upstream and downstream actors, highlighting the prominent role of intramembranous ossification – which takes place at the cranial sutures – in influencing cranial vault shape. We found that mutations in many genes associated with craniosynostosis exert their pathogenicity by modulating the same pathways involved in normal cranial vault development. This was further demonstrated in a non-syndromic sagittal craniosynostosis case-parent trio dataset of 63 probands (n = 189), where our GWAS signals nearBMP2, BBS9, andZIC2contributed significantly to disease risk. Moreover, we found strong evidence of overlap with genes influencing the morphology of the face and the brain, suggesting a common genetic architecture connecting these developmentally adjacent structures. Overall, our study provides a comprehensive overview of the genetics underlying normal cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
The secretome of irradiated peripheral mononuclear cells attenuates hypertrophic skin scarring
Authors: Vorstandlechner Vera , Copic Dragan , Klas Katharina , Direder Martin , Golabi  , Radtke Christine , Ankersmit Hendrik J. , Mildner Michael 
Published: December 2022

AbstractBackgroundHypertrophic scars can cause pain, movement restrictions, and reduction of quality of life. Despite numerous options to tackle hypertrophic scarring, efficient therapies are still scarce, and cellular mechanisms are not well understood. Secreted factors from peripheral blood mononuclear cells (PBMCsec) were previously described for their beneficial effects in tissue regeneration. Here, we investigated the effects of PBMCsec on skin scarring in mouse models and human scar explant cultures at single cell resolution (scRNAseq).MethodsMouse wounds and scars were treated with PBMCsec either intradermally or topically. Human mature scars were treated with PBMCsec ex vivo in explant cultures. All experimental settings were analyzed by single cell RNA sequencing (scRNAseq). A variety of bioinformatics approaches were used to decipher gene regulation in the scRNAseq data sets. Components of the extracellular matrix (ECM) were investigated in situ by immunofluorescence. The effect of PBMCsec on myofibroblast differentiation and elastin expression was investigated by stimulating human primary fibroblasts with TGFβ.FindingsTopical and intradermal application of PBMCsec regulated the expression of a variety of genes involved in pro-fibrotic processes and tissue remodeling. Our bioinformatics approach identified elastin as a common linchpin of antifibrotic action in both, the mouse and human experimental setting.In vitro, we found that PBMCsec prevents TGFβ-mediated myofibroblast-differentiation and attenuates abundant elastin expression through non-canonical signaling inhibition. Furthermore, TGFβ-induced breakdown of elastic fibers was strongly inhibited by addition of PBMCsec.InterpretationTogether, we showed anti-fibrotic effect of PBMCsec on cutaneous scars in mouse and human experimental settings, suggesting PBMCsec as a novel therapeutic option to treat skin scarring.Research in contextEvidence before this studyParacrine factors secreted from irradiated peripheral mononuclear cells (PBMCsec) show strong tissue regenerative properties in a variety of organs and are shown to enhance cutaneous wound healing. Whether PBMCsec shows anti-fibrotic properties on scar formation has not been investigated so far.Added value of this studyIn the present study, we were able to demonstrate that PBMCsec improves quality of developing and mature scars in mouse and human scar tissue. We found that PBMCsec is able to attenuate the expression of various genes, promoting scar formation and inhibit TGFβ-induced myofibroblast differentiation. Elastin and TXNIP were identified as a common linchpin of its anti-fibrotic action.Implications of all the available evidenceUsingin vivo, ex vivo, andin vitromodels and analyses on a single-cell level, our study paves the way for clinical studies evaluating the use of PBMCsec for the treatment of human cutaneous scars.