bluuebunny/crossref_metadata_2025_split huggingface dataset:
AraMultiOmics: a tool for generating multi-omics features for downstream statistical analysis to infer the molecular basis of symbiosis among non-host plant Arabidopsis thaliana, host plant, and arbuscular mycorrhizal fungi
Authors: Kang Jee Eun 
Published: November 2023

AbstractArbuscular mycorrhizal fungi (AMF) are symbiotic microorganisms that colonize plant roots, promoting plant growth and improving soil quality. A large number of studies have focused on investigating the communication between host-plants and AMF. Recent investigation in molecular evolution related to arbuscular mycorrhizal symbiosis in Arabidopsis thaliana (A. thaliana) have enabled scientists to perform comparative multi-omics analyses between A. thaliana and host-plants. Although there is a vast amount of omics data available for A. thaliana, most AM-related information comes from differentially expressed genes (DEG) identified in transcriptome studies. To address this gap, we developed AraMultiOmics, a useful tool for integrative analysis of multi-omics data of A. thaliana. It consists of 10 modules: 1) epigenetic regulations in protein–nucleic acid interaction (PNI), 2) DNA structure and metal binding profile, 3) transcription factor (TF) binding profiles, 4) protein domain–domain interaction (DDI), 5) profiling of interactions of protein-metal and of protein-ligand with complex structures (PLP) based on alignment of similar protein structures, 6) carbohydrate-lipid-protein interaction (CLP)- analysis of lipidome-proteome-glycoscience, 7) metabolic pathway analysis, 8) multiple omics association study, 9) GO/PO analysis, and 10) Medicago COG information. These analyses are conducted in comparison with the COG of Medicago truncatula (M. truncatula). To facilitate the inference of AM-driven changes and of AM derived molecules during AM symbiosis, the program provides a convenient means to generate datasets with important features that can be conjoined with various downstream statistical methods. We have included demonstrations on how to create comparative datasets, and the program codes are freely available for download atwww.artfoundation.kr.
Murine uterine gland branching is necessary for gland function in implantation
Authors: Granger Katrina , Fitch Sarah , Shen May , Lloyd Jarrett , Bhurke Aishwarya , Hancock Jonathan , Ye Xiaoqin , Arora Ripla 
Published: November 2023

ABSTRACTUterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation, however contribution of uterine gland structure to gland secretions such as LIF is not known. Here we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma and muscle using the progesterone receptorPgrCrecauses a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a mullerian duct Cre line -Pax2Cre, displays gland bud elongation but a failure in gland branching. Surprisingly, adult uterine epithelial deletion of ESR1 using the lactoferrin-Cre (LtfCre) displays normally branched uterine glands. Intriguingly, unbranched glands fromPax2CreEsr1flox/floxuteri fail to express glandular pre-implantationLif,preventing implantation chamber formation and embryo alignment along the uterine mesometrial-antimesometrial axis. In contrast, branched glands fromLtfCreEsr1flox/floxuteri display reduced expression of glandularLifresulting in delayed implantation chamber formation and embryo-uterine axes alignment but deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice expressLifin the luminal epithelium but fail to expressLifin the glandular epithelium even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandularLifexpression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure-function contributes to pregnancy success.
Butyrate-producing bacteria as probiotic supplement: beneficial effects on metabolism and modulation of behavior in an obesity mouse model
Authors: Garcia-Serrano Alba M. , Skoug Cecilia , Axling Ulrika , Korhonen Emma Rosmariini , Teixeira Cristina , Ahrén Irini Lazou , Mukhopadhya Indrani , Boteva Nikoleta , Martin Jennifer , Scott Karen , Gratz Silvia , Stenkula Karin G. , Holm Cecilia , Duarte João M.N. 
Published: November 2023

AbstractObesity is a risk factor for cardio-metabolic and neurological disease. The contribution of gut microbiota to derangements of the gut-brain axis in the context of obesity has been acknowledged, particularly through physiology modulation by short-chain fatty acids (SCFAs). Thus, probiotic interventions and administration of SCFAs have been employed with the purpose of alleviating symptoms in both metabolic and neurological disease. We have tested the effects of four butyrate-producing bacteria from the Lachnospiraceae family on the development of metabolic syndrome and behavioural alterations in a mouse model of diet-induced obesity. Male mice were fed either a high-fat diet (HFD) or an ingredient-matched control diet for 2 months, and bacteria cultures or culture medium were given by gavage to HFD-fed mice every second day. Assessment of the mice through a battery of metabolic and behaviour tests revealed that one of the administered bacteria affords some degree of protection against the development of obesity and its complications.
Genotype combinations drive variability in the microbiome configuration of the rhizosphere of Maize/Bean intercropping system
Authors: Lanzavecchia Giovanna , Frascarelli Giulia , Rocchetti Lorenzo , Bellucci Elisa , Bitocchi Elena , Di Vittori Valerio , Sillo Fabiano , Ferraris Irene , Carta Giada , Delledonne Massimo , Nanni Laura , Papa Roberto 
Published: November 2023

AbstractIn intercropping system, the interplay between cereals and legumes, which is strongly driven by complementarity of below-ground structures and their interactions with the soil microbiome, raises a fundamental query: Can different genotypes alter the configuration of the rhizosphere microbial communities? To address this issue, we conducted a field study, probing the effects of intercropping and diverse maize (Zea maysL.) and beans (Phaseolus vulgarisL.,Phaseolus coccineusL.) genotype combinations. Our results unveil that intercropping condition alters the rhizosphere bacterial communities, but that the degree of this impact is substantially affected by specific genotype combinations. Overall, intercropping allows the recruitment of exclusive bacterial species and enhance community complexity. Nevertheless, combinations of maize and beans genotypes determine two distinct groups characterized by higher or lower bacterial community diversity and complexity, which are influenced by the specific bean line associated. Moreover, intercropped maize lines exhibit varying propensities in recruiting bacterial members with more responsive lines showing preferential interactions with specific microorganisms. Our study conclusively shows that genotype has an impact on the rhizosphere microbiome and that a careful selection of genotype combinations for both species involved is essential to achieve compatibility optimization in intercropping.
AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans
Authors: Houston Brendan J. , Nguyen Joseph , Merriner D. Jo , O’Connor Anne E. , Lopes Alexandra M. , Nagirnaja Liina , Friedrich Corinna , Kliesch Sabine , Tüttelmann Frank , Aston Kenneth I. , Conrad Donald F. , Hobbs Robin M. , Dunleavy Jessica EM , O’Bryan Moira K. 
Published: November 2023

AbstractDynein complexes are large, multi-unit assemblies involved in many biological processes including male fertility via their critical roles in protein transport and axoneme motility. Previously we identified a pathogenic variant in the dynein geneAXDND1in an infertile man. Subsequently we identified an additional four potentially compound heterozygous variants of unknown significance inAXDND1in two additional infertile men. We thus tested the role of AXDND1 in mammalian male fertility by generating a knockout mouse model.Axdnd1-/-males were sterile at all ages but could undergo one round of histologically complete spermatogenesis. Subsequently, a progressive imbalance of spermatogonial commitment to spermatogenesis over self-renewal occurred, ultimately leading to catastrophic germ cell loss, loss of blood-testis barrier patency and immune cell infiltration. Sperm produced during the first wave of spermatogenesis were immotile due to abnormal axoneme structure, including the presence of ectopic vesicles and abnormalities in outer dense fibres and microtubule doublet structures. Sperm output was additionally compromised by a severe spermiation defect and abnormal sperm individualisation. Collectively, our data highlight the essential roles of AXDND1 as a regulator of spermatogonial commitment to spermatogenesis and during the processes of spermiogenesis where it is essential for sperm tail development, release and motility.
Candida albicanssuppression of neutrophil reactive nitrogen species is rescued by host Hif-1αin vivo
Authors: Burgess Thomas B. , Hammond Ffion R. , Szkuta Piotr T. , Lewis Amy , Christou Stella , Ayscough Kathryn R. , Johnston Simon A. , Condliffe Alison M. , Elks Philip M. 
Published: November 2023

AbstractCandidaspp. cause 750,000 cases per annum of invasive disease worldwide, with up to a 50% mortality rate. Poor efficacy of current antifungals, lack of vaccines and rising antifungal resistance rates point towards an urgent need to develop new therapies.Candida albicansis a human commensal fungus that can cause life-threatening invasive infection in immunocompromised individuals.C. albicansis able to manipulate host macrophages and neutrophils to escape phagosomal killing and has previously been shown to suppress reactive nitrogen species (RNS) productionin vitro. However, the effects ofC. albicanson RNSin vivoand the molecular and cellular mechanisms involved remain unclear. Using a zebrafish model, we aimed to characterise RNS suppression byC. albicans in vivo. We demonstrate thatC. albicanssuppressed neutrophil RNS both proximally and distally to the infection site in a partially active process, with heat-killedC. albicansnot reducing RNS to the same extent as live fungi. Using acar1Δ mutant, we show that fungal arginase is partially responsible for the reduction in neutrophil RNS. Stabilisation of Hif-1α, a transcription factor with a key role in immune regulation, rescued neutrophil RNS production duringC. albicansinfection, leading to improved infection outcomes. The protective effect of Hif-1α stabilisation was neutrophil- and nitric oxide synthase-dependent. Together, these data demonstrate that Hif-1α stabilisation can restore the neutrophil RNS response inC. albicansinfection, leading to improved infection outcomes, highlighting the potential of targeting Hif-1α and RNS in host directed therapies against fungal infections.
Haptenic adducts of β-lactam antibiotics elicit antibody responses with narrow clonality and specificity
Authors: Deimel Lachlan P. , Moynié Lucile , Sun Guoxuan , Lewis Viliyana , Turner Abigail , Buchanan Charles J. , Burnap Sean A. , Kobras Carolin M. , Stracy Mathew , Struwe Weston B. , Baldwin Andrew J. , Naismith James , Davis Benjamin G. , Sattentau Quentin J. 
Published: November 2023

AbstractMany classes of small-molecule drugs form protein adductsin vivo, which may elicit antibodies via a classical hapten-carrier-type response, with implications for both allergy and drug sequestration. Although β-lactam antibiotics are a drug class long associated with these phenomena, the molecular determinants of drug-protein conjugation and consequent drug-specific immune responses remain incomplete. Here, we interrogated factors influencing penicilloyl adduct formation and immunogenicity, and used penicillin G (PenG) to probe the B and T cell determinants of drug-specific IgG responses in mice. We identify through deep clonotyping a dominant murine penicilloyl-specific clonal antibody class encompassing phylogenetically relatedIGHV1,IGHV5andIGHV10subgroup gene segments. Through protein NMR and x-ray structural analysis, we determined that adduct specific antibody clones—the MIL series—predominantly recognise the variable side-chain moiety (which for PenG is phenylacetamide) via a hydrophobic pocket, while secondary H-bond contacts with both thiazolidine and the adducted lysine residue is made. As a result, the cross-reactivity against other β-lactam antibiotics is limited. These data demonstrate the relationship between the chemistry of protein-reactive drugs such as penicilloyls, and how their predisposition to generating B cell responses can inform the functional implications at the clonal level.Highlights-PenG readily forms immunogenic adducts on lysine sidechains of diverse self- and non-self proteins including complete serum under physiological conditions.-PenG-protein adductionin vitroorin vivois sufficient to elicit penicillin-specific IgG responses.-Murine B cell clonotypic responses are characterised by near-uniform antibody binding modes of similar immunogenetic origin.-The dominant murine PenG-specific clonotype is dominated by benzene ring recognition and correlates with serological cross-reactivity profiles.
Non-canonical hepatic androgen receptor mediates glucagon sensitivity in female mice through the PGC1α/ERRα/mitochondria axis
Authors: Chen Jie , Wu Yuanyuan , Hao Wanyu , You Jia , Wu Lianfeng 
Published: November 2023

AbstractThe hormone glucagon plays a crucial role in maintaining normal blood glucose levels and has recently been found to promote liver lipid catabolism in both clinical and basic research studies. However, the mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. Here, we report that hepatic androgen receptor (AR) functions as a critical mediator of glucagon signaling, contributing to sexual dimorphism in hepatic glucagon sensitivity. The inhibition of AR, either through chemical or genetic means, impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes. Notably, female mouse hepatocytes express up to three times more AR than their male littermates. Consequently, they respond to glucagon to a much greater extent in terms of glucose production and lipid catabolism outcomes. Moreover, liver-specific AR knockout impairs the effect of glucagon in inducing blood glucose production, especially in female mice. Mechanistically, we demonstrate that hepatic AR drives a PGC1α/ERRα-mitochondria axis to promote lipid catabolism for liver glucose production in response to glucagon treatment. Together, our study sheds light on the role of hepatic AR in mediating glucagon activity in orchestrating glucose and lipid metabolism, particularly in female mice. These findings may help elucidate the factors responsible for sex differences in glucagon sensitivity and the development of fatty liver disease.
Predicting subject traits from brain spectral signatures: an application to brain ageing
Authors: Jarne Cecilia , Griffin Ben , Vidaurre Diego 
Published: November 2023

AbstractThe prediction of subject traits using brain data is an important goal in neuroscience, with relevant applications in clinical research, as well as in the study of differential psychology and cognition. While previous prediction work has predominantly been done on neuroimaging data, our focus is on electroencephalography (EEG), a relatively inexpensive, widely available and non-invasive data modality. However, EEG data is complex and needs some form of feature extraction for subsequent prediction. This process is sometimes done manually, risking biases and suboptimal decisions. Here we investigate the use of data-driven kernel methods for prediction from single-channels using the the EEG spectrogram, which reflects macro-scale neural oscillations in the brain. Specifically, we introduce the idea of reinterpreting the the spectrogram of each channel as a probability distribution, so that we can leverage advanced machine learning techniques that can handle probability distributions with mathematical rigour and without the need for manual feature extraction. We explore how the resulting technique, Kernel Mean Embedding Regression, compares to a standard application of Kernel Ridge Regression as well as to a non-kernelised approach. Overall, we found that the kernel methods exhibit improved performance thanks to their capacity to handle nonlinearities in the relation between the EEG spectrogram and the trait of interest. We leveraged this method to predict biological age in a multinational EEG data set, HarMNqEEG, showing the method’s capacity to generalise across experiments and acquisition setups.
Thein vitrodynamics of pseudo-vascular network formation
Authors: Oraiopoulou Mariam-Eleni , Couturier Dominique-Laurent , Bunce Ellie V. , Cannell Ian , Golinska Monika , Hannon Gregory , Sakkalis Vangelis , Bohndiek Sarah E. 
Published: November 2023

AbstractPseudo-vascular network formation capacityin vitrois considered a key characteristic of vasculogenic mimicry. While many cancer cell lines are known to form pseudo-vascular networks, little is known about the spatiotemporal dynamics of these formations. Here, we present a framework for monitoring and characterising the dynamic formation and dissolution of pseudo-vascular networksin vitro. The framework combines time-resolved optical microscopy with open-source image analysis for network feature extraction and statistical modelling. The framework is demonstrated by comparing diverse cancer cell lines associated with vasculogenic mimicry, then in detecting response to drug compounds proposed to affect formation of vasculogenic mimics. Dynamic datasets collected were analysed morphometrically and a descriptive statistical analysis model was developed in order to measure stability and dissimilarity characteristics of the pseudo-vascular networks formed. Melanoma cells formed the most stable pseudo-vascular networks and were selected to evaluate the response of their pseudo-vascular networks to treatment with axitinib, brucine and tivantinib. Our framework is shown to enable quantitative analysis of both the capacity for network formation, linked vasculogenic mimicry, as well as dynamic responses to treatment.
Pericytes promote more angiogenesis and vasculogenesis than mesenchymal stromal cells in microfluidic chips
Authors: Gonzalez-Rubio Julian , Kubiza Hannah , Koenigs-Werner Hiltrud , Jockenhoevel Stefan , Cornelissen Christian G. , Thiebes Anja Lena 
Published: November 2023

AbstractThe pericyte is a key player in vascularization, protecting endothelial cells from external harm and promoting formation of new vessels and connections when necessary. However, pericytic identity and its relation with other cell types, such as the mesenchymal stromal/stem cells, is highly debated. To compare the behaviour of pericytes and unselected stromal cells in vascularization, we used multichannel microfluidic chips to replicate the two processes of vessel formation: vasculogenesis, thede novovessel formation, and angiogenesis, the sprouting of new vessels from existing ones. In angiogenesis, pericytes promote significantly more and longer sproutings than stromal cells. In vasculogenesis, stromal cells promote the formation of structures ressembling the embryonic capillary plexus, whereas pericytes wrap around the endothelial cells, arresting their division and forcing them into tubulogenesis. Whole-transcriptome sequencing confirms an upregulation of pro-vascularization and cytostatic genes in co-cultures of pericytes and endothelial cells; while stromal cells strongly stimulate mitosis and organelle biogenesis pathways and decrease the release of pro-inflammatory cytokines. In this study, we offer new insights into the pericyte-endothelial cell relation and the mesenchymal stromal cell elusive identity, relevant in both vascular biology and tissue engineering.
aHISplex: an imputation based method for eye, hair and skin colour prediction from low coverage ancient DNA
Authors: Maróti Zoltán , Nyerki Emil , Neparaczki Endre , Török Tibor , Varga Gergely István , Kalmár Tibor 
Published: November 2023

AbstractThe prediction of externally visible traits (eye, hair and skin colours) from DNA can provide valuable information for both contemporary and ancient human populations. The validated HIrisPlex-S method is the primary tool in forensics for phenotyping modern samples. The HIrisPlex-S multiplex PCR assay can handle trace DNA from modern samples, but the analysis of degraded, low coverage ancient DNA (aDNA) presents additional challenges. Genotype imputation has recently proven successful in effectively filling in missing information in aDNA sequences. To assess the feasibility of this approach, we evaluated how key factors, such as genome coverage, minor allele frequency, extent of post mortem damage, and the population origin of the test individual influence the efficiency of imputing HIrisPlex-S markers and predicting phenotypes. We used high coverage sequence data from ancient remains for the evaluation. Our results demonstrate that even with genome coverages as low as 0.1-0.5x, the proposed workflow is capable of predicting phenotypes from degraded ancient (or forensic) WGS data with good accuracy. To aid the archaeogenetics community, we have developed a user-friendly, easily deployable imputation-based framework that includes the new bioinformatics tools and the pre-made reference data sets required for the whole analysis.
HPV and p53 status as precision determinants of head and neck cancer response to DNA-PKcs inhibition in combination with irradiation
Authors: Hayrapetyan Liana , Roth Selina M. , Hovhannisyan Lusine , Medo Matúš , Quintin Aurélie , Ott Julien , Albers Joachim , Aebersold Daniel M. , Zimmer Yitzhak , Medová Michaela 
Published: November 2023

AbstractMajor risk factors of head and neck squamous cell carcinoma (HNSCC) are tobacco use and human papillomavirus (HPV). HPV E6 oncoprotein leads to the degradation of the p53 protein, whereas HPV-negative cancers are frequently associated with TP53 mutations. Peposertib is a potent and selective, orally administered small-molecule inhibitor of the catalytic subunit of the DNA-dependent kinase (DNA-PKcs), a key regulator of non-homologous end joining (NHEJ). NHEJ inhibition along with irradiation (IR)-induced DNA double-strand breaks has the potential to increase antitumor treatment efficacy. Here, we investigated the responses of HNSCC models with distinct HPV and p53 status to treatments with IR, DNA-PKcs inhibition, and their combination.We observed that IR-induced DNA damage combined with peposertib administration shortly before IR results in decreased cell viability and proliferation and causes DNA repair delay in all the studied HNSCC cell lines. However, our data confirm that the actual cell fate upon this treatment is strongly dependent on cellular p53/HPV status. Cells lacking functional p53 due to its degradation by HPV or due to the presence of a loss-of-function mutation are arrested in the G2 phase of the cell cycle and eliminated by apoptosis whereas p53-proficient HNSCC cell lines undergo senescence. Consequently, HPV+ cancer cell lines and xenografts display stronger and more durable responses and seem to benefit from the combined treatment more than p53-proficient HNSCCs. In conclusion, DNA-PKcs inhibitor peposertib should be further studied as a potential radiosensitizer for HNSCCs, taking into consideration the genetic background and the HPV status of a particular tumor.