bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel genetic regions associated with resistance to European canker in apple
Authors: Karlström Amanda , Gómez-Cortecero Antonio , Nellist Charlotte F , Ordidge Matthew , Dunwell Jim M. , Harrison Richard J 
Published: December 2021

AbstractResistance to Neonectria ditissima, the fungus causing European canker in apple, was studied in a multiparental population of apple scions using several phenotyping methods. The studied population consists of individuals from multiple families connected through a common pedigree. The degree of disease of each individual in the population was assessed in three experiments: artificial inoculations of detached dormant shoots, potted trees in a glasshouse and in a replicated field experiment. The genetic basis of the differences in disease was studied using a pedigree-based analysis (PBA). Three quantitative trait loci (QTL), on linkage groups (LG) 6, 8 and 10 were identified in more than one of the phenotyping strategies. An additional four QTL, on LG 2, 5, 15 and 16 were only identified in the field experiment. The QTL on LG2 and 16 were further validated in a biparental population. QTL effect sizes were small to moderate with 4.3 to 19 % of variance explained by a single QTL. A subsequent analysis of QTL haplotypes revealed a dynamic response to this disease, in which the estimated effect of a haplotype varied over the field time-points. Two groups of QTL-haplotypes could be distinguished, one that displayed increased effect and one with a constant effect across time-points. These results suggest that there are different modes of control of N. ditissima in the early stages of infection compared to later time-points of disease development. It also shows that multiple QTL will need to be considered to improve resistance to European canker in apple breeding germplasm.
Endogenous DAF-16 Spatiotemporal Activity Quantitatively Predicts Lifespan Extension Induced by Dietary Restriction
Authors: Huayta Javier , San-Miguel Adriana 
Published: December 2021

SummaryIn many organisms, dietary restriction (DR) leads to lifespan extension through the activation of cell protection and pro-longevity gene expression programs. In the nematode C. elegans, the DAF-16 transcription factor is a key aging regulator that governs the Insulin/IGF-1 signaling pathway and undergoes translocation from the cytoplasm to the nucleus of cells when animals are exposed to food limitation. In this work, we assess the endogenous activity of DAF-16 under various DR regimes by coupling CRISPR/Cas9-enabled fluorescent tagging of DAF-16 with quantitative image analysis and machine learning. Our results indicate that lifelong DAF-16 endogenous activity is a robust predictor of mean lifespan in C. elegans, and it accounts for 78% of the lifespan variability induced by DR. We found that this lifespan-extending mechanism occurs mainly in the intestine and neurons, and that DR drives DAF-16 activity in unexpected locations such as the germline and intestinal nucleoli.
Transcriptional signature in microglia isolated from an Alzheimer’s disease mouse model treated with scanning ultrasound
Authors: Leinenga Gerhard , Bodea Liviu-Gabriel , Schröder Jan , Sun Giuzhi , Chen Yi , Grubman Alexandra , Polo Jose M. , Götz Jürgen 
Published: December 2021

AbstractRationaleIntracranial scanning ultrasound combined with intravenously injected microbubbles (SUS+MB) has been shown to transiently open the blood-brain barrier and reduce amyloid-β (Aβ) pathology in the APP23 mouse model of Alzheimer’s disease (AD). This has been accomplished, at least in part, through the activation of microglial cells; however, their response to the SUS treatment is only incompletely understood.MethodsWild-type (WT) and APP23 mice were subjected to SUS+MB, using non-SUS+MB-treated mice as sham controls. After 48 hours, the APP23 mice were injected with methoxy-XO4 to label Aβ aggregates, followed by microglial isolation into XO4+and XO4-populations using flow cytometry. Both XO4+and XO4-cells were subjected to RNA sequencing and their transcriptome was analyzed through a bioinformatics pipeline.ResultsThe transcriptomic analysis of the microglial cells revealed a clear segregation depending on genotype (AD model versus WT mice), as well as treatment (SUS+MBversus sham) and Aβ internalization (XO4+versus XO4-microglia). Differential gene expression analysis detected 278 genes that were significantly changed by SUS+MBin the XO4+cells (248 up/30 down) and 242 in XO-cells (225 up/17 down). Not surprisingly given previous findings of increased phagocytosis of plaques following SUS+MB, the pathway analysis highlighted that the treatment induced an enrichment in genes related to the phagosome pathway in XO4+microglia; however, when comparing SUS+MBto sham, the analysis revealed an enrichment in genes involved in the cell cycle in both the XO4+and XO4-microglial population.ConclusionOur data provide a comprehensive analysis of microglia in an AD mouse model subjected to ultrasound treatment as a function of Aβ internalization, one of the defining hallmarks of AD. Several differentially expressed genes are highlighted, pointing to an ultrasound-induced activation of cell cycle mechanisms in microglial cells isolated from APP23 mice treated with SUS+MB.Graphical abstract
Intestinal Enteroid Monolayers Model the Human Intestinal Environment for Escherichia coli Infection
Authors: Small Jason , Weiss Alison 
Published: December 2021

AbstractEnterohemorrhagic Escherichia coli O157:H7 is an enteric pathogen responsible for bloody diarrhea, hemolytic uremic syndrome, and in severe cases even death. The study of O157:H7 is difficult due to the high specificity of the bacteria for the human intestine, along with our lack of sufficiently complex human cell culture models. The recent development of human intestinal enteroids derived from intestinal crypt multipotent stem cells has allowed us to construct 2-dimensional differentiated epithelial monolayers grown in transwells that mimic the human intestine. Unlike previous studies, saline was added to the apical surface, while maintaining culture media in the basolateral well. The monolayers continued to grow and differentiate with apical saline. Apical infection with O157:H7 or commensal E. coli resulted in robust bacterial growth from 105 to over 108 over 24 hours. Despite this robust bacterial growth, commensal E. coli neither adhered to nor damaged the epithelial barrier over 30 hours. However, O157:H7 was almost fully adhered (>90%) by 18 hours with epithelial damage observed by 30 hours. O157:H7 contains the locus of enterocyte effacement (LEE) pathogenicity island responsible for attachment and damage to the intestinal epithelium. Previous studies report the ability of nutrients such as biotin, D-serine, and L-fucose to downregulate LEE gene expression. O157:H7 treated with biotin or L-fucose, but not D-serine displayed both decreased attachment and reduced epithelial damage over 36 hours. These data illustrate enteroid monolayers can serve as a suitable model for the study of O157:H7 pathogenesis, and identification of potential therapeutics.ImportanceO157:H7 is difficult to study due to its high specificity for the human intestine and the lack of sufficiently complex human cell culture models. The recent development of human intestinal enteroids derived from intestinal crypt multipotent stem cells has allowed us to construct 2-dimensional differentiated epithelial monolayers grown in transwells that mimic the human intestine. Our data illustrates enteroid monolayers can serve as a suitable model for the study of O157:H7 pathogenesis, and allow for identification of potential therapeutics.
5-aminolevulinic acid-photodynamic therapy ameliorates cutaneous granuloma by killing drug-resistant Mycobacterium marinum
Authors: Yang Zhiya , Feng Yahui , Pang Zhiping , Li Dongmei , Wang Sisi , Chen Huiqi , Jiang Mingze , Yan Hongxia , Li Tianhang , Fu Hongjun , Xiong Hubao , Shi Dongmei 
Published: December 2021

AbstractBackgroundAlthough 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been extensively used to treat to various skin disease, the application of ALA-PDT on cutaneous infection caused by Mycobacterium marinum (M. marinum), especially by drug-resistant M. marinum is still not clear.ObjectivesWe evaluated the therapeutic efficacy of ALA-PDT on M. marinum in a mouse infection model and tested its killing effect on M. marinum in vitro. Finally, we investigated the clinical effect of ALA-PDT in treating cutaneous granuloma caused by drug-resistant M. marinum.Materials and methodsWe isolated total 9 strains of M. marinum from patients and confirmed by morphological and molecular approaches. The strains were identified by anti-mycobacterial susceptibility. Then we evaluated the killing effect of ALA-PDT on M. marinum in vitro and in a mouse model to observe the antimycobacterial effect of ALA-PDT. Therapeutic efficacy was further assessed in patients with cutaneous granuloma caused by drug-resistant M. marinum.ResultsWe demonstrated that the ALA-PDT directly killed M. marinum in vitro. The paws cutaneous lesions of mice caused by M. marinum were fully recovered 2 weeks after ALA-PDT treatment. However, there was no significant difference for immune cells in peripheral blood before and after ALA-PDT therapy. Finally, ALA-PDT proved to be effective in treat two patients with cutaneous infection caused by drug-resistant M. marinum.ConclusionsThe results suggest that ALA-PDT is effective in treating M. marinum cutaneous infections by killing M. marinum directly, independent of systemic immune responses. The data highlight the ALA-PDT as a promising therapeutic choice for M. marinum infection, especially for drug-resistant strains.
Breakthrough Infections with SARS-CoV-2 in Vaccinated Students After a Festive Event – Identification of Risk Factors
Authors: Bertram Ralph , Bartsch Vanessa , Sodmann Johanna , Hennig Luca , Müjde Engin , Stock Jonathan , Ruedig Vivienne , Sodmann Philipp , Todt Daniel , Steinmann Eike , Hitzl Wolfgang , Steinmann Joerg 
Published: December 2021

AbstractWe report an outbreak with SARS-CoV-2 breakthrough infections related to a festive event in Northern Bavaria, Germany in October 2021, with 24 of 95 participants infected. Correlation analyses among 15 interrogated variables revealed that duration at the event and conversation with the supposed index person were significant risk factors.Article Summary LineThe risk of infection with SARS-CoV-2 in a vaccinated cohort associated with a private festive event was significantly increased upon conversation with the putative index person and positively correlated to the duration of stay at the event.
Hydroxychloroquine in the Pregnancies of Women with Lupus: A Meta-Analysis of Individual Participant Data
Authors: Clowse Megan E. B. , Eudy Amanda M. , Balevic Stephen , Sanders-Schmidler Gillian , Kosinski Andrzej , Fischer-Betz Rebecca , Gladman Dafna , Molad Yair , Nalli Cecilia , Mokbel Abir , Tincani Angela , Urowitz Murray , Bay Caroline , van Noord Megan , Petri Michelle 
Published: December 2021

AbstractObjectiveMultiple guidelines recommend continuing hydroxychloroquine (HCQ) for systemic lupus erythematosus (lupus) during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to combine multiple datasets to compare pregnancy outcomes in women with lupus on and off HCQ.MethodsEligible studies included prospectively-collected pregnancies in women with lupus. After a manuscript search, 7 datasets were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset and results were aggregated to provide a pooled odds ratio.ResultsSeven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a 1st trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared to pregnancies without HCQ, those with HCQ had lower rates of highly active lupus, but did not have different rates of fetal loss, preterm birth, or preeclampsia. Among women with low lupus activity, HCQ reduced the risk for preterm delivery.ConclusionThis large study of prospectively-collected lupus pregnancies demonstrates a decrease in SLE activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy.
Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breastfeeding
Authors: Sajadi Mohammad M. , Shokatpour Narjes , Bathula Allison , Tehrani Zahra Rikhtegaran , Lankford Allison , Purcell Madeleine , Campbell James D. , Hammershaimb Elizabeth Adrianne , Deatrick Kristopher B. , Bor Casey , Parsell Dawn M. , Dugan Colleen , Levine Andrea R. , Ramelli Sabrina C. , Chertow Daniel S. , Herr Daniel L , Lewis George K. , Grazioli Alison 
Published: December 2021

AbstractAlthough there have been many studies on antibody responses to SARS-CoV-2 in breastmilk, very few have looked at the fate of these in the baby. We carried out a study in 22 mother/baby pairs (mothers who breastfed and who were SARS-CoV-2 vaccinated before or after delivery) looking at mother blood, mother milk, baby blood, baby nose, and baby stool. Breastfed infants only acquired systemic anti-SARS-CoV-2 IgG antibodies if their mothers were vaccinated antepartum. None of the infants had SARS-CoV-2-specific IgA in the blood, but surprisingly, half of the infants in the Antepartum group had high titer SARS-CoV-2-specific IgA in the nose that exceeded titers found in breastmilk. Vaccination antepartum followed by breastfeeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants.
Taiwan Biobank: a rich biomedical research database of the Taiwanese population
Authors: Feng Yen-Chen Anne , Chen Chia-Yen , Chen Tzu-Ting , Kuo Po-Hsiu , Hsu Yi-Hsiang , Yang Hwai-I , Chen Wei J. , Shen Chen-Yang , Ge Tian , Huang Hailiang , Lin Yen-Feng 
Published: December 2021

AbstractThe Taiwan Biobank (TWB) is an ongoing prospective study of over 150,000 individuals aged 30-70 recruited from across Taiwan beginning in 2012. A comprehensive list of phenotypes was collected for each consented participant at recruitment and follow-up visits through structured interviews and physical measurements. Biomarkers and genetic data were also generated for all participants from blood and urine samples. We present here an overview of the genetic data quality, population structure, and familial relationship within TWB, which consists of predominantly Han Chinese-ancestry individuals, and highlight important attributes and genetic findings thus far from the biobank. A linkage to Taiwan’s National Health Insurance database of >25 years and other health-related registries is underway that will enrich the phenotypic spectrum of TWB and enable deep and longitudinal genetic investigations. TWB provides one of the largest biobank resources for biomedical and public health research in East Asia that will contribute to our understanding of the genetic basis of human health and disease in global populations through collaborative studies with other biobanks.
Applying computer vision to digitised natural history collections for climate change research: temperature-size responses in British butterflies
Authors: Wilson Rebecca J , de Siqueira Alexandre Fioravante , Brooks Stephen J , Price Benjamin W , Simon Lea M , van der Walt Stéfan J , Fenberg Phillip B 
Published: December 2021

ABSTRACTNatural history collections (NHCs) are invaluable resources for understanding biotic response to global change. Museums around the world are currently imaging specimens, capturing specimen data, and making them freely available online. In parallel to the digitisation effort, there have been great advancements in computer vision (CV): the computer trained automated recognition/detection, and measurement of features in digital images. Applying CV to digitised NHCs has the potential to greatly accelerate the use of NHCs for biotic response to global change research. In this paper, we apply CV to a very large, digitised collection to test hypotheses in an established area of biotic response to climate change research: temperature-size responses.We develop a CV pipeline (Mothra) and apply it to the NHM iCollections of British butterflies (>180,000 specimens). Mothra automatically detects the specimen in the image, sets the scale, measures wing features (e.g., forewing length), determines the orientation of the specimen (pinned ventrally or dorsally), and identifies the sex. We pair these measurements and meta-data with temperature records to test how adult size varies with temperature during the immature stages of species and to assess patterns of sexual-size dimorphism across species and families.Mothra accurately measures the forewing lengths of butterfly specimens and compared to manual baseline measurements, Mothra accurately determines sex and forewing lengths of butterfly specimens. Females are the larger sex in most species and an increase in adult body size with warm monthly temperatures during the late larval stages is the most common temperature size response. These results confirm suspected patterns and support hypotheses based on recent studies using a smaller dataset of manually measured specimens.We show that CV can be a powerful tool to efficiently and accurately extract phenotypic data from a very large collection of digital NHCs. In the future, CV will become widely applied to digital NHC collections to advance ecological and evolutionary research and to accelerate the use of NHCs for biotic response to global change research.
Multiscale selection in spatially structured populations
Authors: Doekes Hilje M. , Hermsen Rutger 
Published: December 2021

AbstractThe spatial structure of natural populations is key to many of their evolutionary processes. Formal theories analysing the interplay between natural selection and spatial structure have mostly focused on populations divided into distinct, non-overlapping groups. Most populations, however, are not structured in this way, but rather (self-)organise into dynamic patterns unfolding at various spatial scales. Here, we present a mathematical framework that quantifies how patterns and processes at different spatial scales contribute to natural selection in such populations. To that end, we define the Local Selection Differential (LSD): a measure of the selection acting on a trait within a given local environment. Based on the LSD, natural selection in a population can be decomposed into two parts: the contribution of local selection, acting within local environments, and the contribution of interlocal selection, acting among them. Varying the size of the local environments subsequently allows one to measure the contribution of each length scale. To illustrate the use of this new multiscale selection framework, we apply it to two simulation models of the evolution of traits known to be affected by spatial population structure: altruism and pathogen transmissibility. In both models, the spatial decomposition of selection reveals that local and interlocal selection can have opposite signs, thus providing a mathematically rigorous underpinning to intuitive explanations of how processes at different spatial scales may compete. It furthermore identifies which length scales—and hence which patterns—are relevant for natural selection. The multiscale selection framework can thus be used to address complex questions on evolution in spatially structured populations.
Ordering and topological defects in social wasps’ nests
Authors: Krishna Shivani , Gopinath Apoorva , Bhattacharjee Somendra M. 
Published: December 2021

AbstractSocial insects have evolved a variety of architectural formations. Bees and wasps are well known for their ability to achieve compact structures by building hexagonal cells.Polistes wattii, an open nesting paper wasp species, builds planar hexagonal structures. Here, using the pair correlation function approach, we show that their nests exhibit short-range hexagonal order (no long-range order) akin to amorphous materials. Hexagonal orientational order was well preserved globally. We also show the presence of topological defects such as dislocations (pentagon-heptagon disclination pairs) and Stone-Wales quadrupoles, and discuss how these defects were organized in the nest, thereby restoring order. Furthermore, we suggest the possible role of such defects in shaping nesting architectures of other social insect species.
SHOT-R: A next generation algorithm for particle kinematics analysis
Authors: Corradi Eloina , Boscheri Walter , Baudet Marie-Laure 
Published: December 2021

AbstractAnalysis of live-imaging experiments is crucial to decipher a plethora of cellular mechanisms within physiological and pathological contexts. Kymograph, i.e. graphical representations of particle spatial position over time, and single particle tracking (SPT) are the currently available tools to extract information on particle transport and velocity. However, the spatiotemporal approximation applied in particle trajectory reconstruction with those methods intrinsically prevents an accurate analysis of particle kinematics and of instantaneous behaviours. Here, we present SHOT-R, a novel numerical method based on polynomial reconstruction of 4D (3D+time) particle trajectories. SHOT-R, contrary to other tools, computesbona fideinstantaneous and directional velocity, and acceleration. Thanks to its high order continuous reconstruction it allows, for the first time, kinematics analysis of co-trafficked particles. Overall, SHOT-R is a novel, versatile, and physically reliable numerical method that achieves all-encompassing particle kinematics studies at unprecedented accuracy on any live-imaging experiment where the spatiotemporal coordinates can be retrieved.
Human gut bifidobacteria inhibit the growth of the opportunistic fungal pathogen Candida albicans
Authors: Ricci Liviana , Mackie Joanna , Donachie Gillian E. , Chapuis Ambre , Mezerová Kristýna , Lenardon Megan D. , Brown Alistair J. P. , Duncan Sylvia H. , Walker Alan W. 
Published: December 2021

ABSTRACTThe human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via mechanisms such as competition for nutrients and by production of antimicrobial compounds. Here, we investigated the antagonist activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections and mortality in susceptible patients. Co-culture batch incubations of C. albicans in the presence of faecal microbiota from six different healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene sequence profiling of these faecal co-culture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow up mechanistic studies confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro under both aerobic and anaerobic conditions. Production of the fermentation acids acetate and lactate, together with the concomitant decrease in pH, were strong drivers of the inhibitory activity. Bifidobacteria may therefore represent attractive targets for the development of probiotics and prebiotic interventions tailored to enhance inhibitory activity against C. albicans in vivo.