bluuebunny/crossref_metadata_2025_split huggingface dataset:
lincRNA RP24-315D19.10 promotes endometrial decidualization via upregulation of hnRNPA2B1
Authors: Tan Liping , Gao Rufei , Chen Xuemei , Geng Yanqing , Yin Xin , Chuan Peng , Mu Xinyi , Su Yan , Zhang Yan , Li Fangfang , He Junlin 
Published: September 2022

AbstractSufficient decidualization is necessary to maintain successful pregnancy. The physiological function and underlying molecular mechanisms of intergenic long non-coding RNA (lincRNAs) in this process remain largely unknown. Herein, we identified a lincRNA, RP24-315D19.10, which is highly expressed during mouse decidualization during early pregnancy, by performing RNA-sequencing (RNA-seq) analysis and weighted gene co-expression network analysis (WGCNA). Detailed cell and molecular assays revealed that lincRNA RP24-315D19.10 knockdown blocked decidualization in primary mouse endometrial stromal cells (mESCs), suggesting that RP24-315D19.10 is a promoting factor for decidualization. Mechanistically, cytoplasmic RP24-315D19.10 directly interacted with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and upregulated its protein level. Moreover, we found that hnRNPA2B1 is involved in the regulation of decidualization through loss- and gain-of-function studiesin vitro. Clinically, patients diagnosed with spontaneous miscarriage were found to have lower hnRNPA2B1 levels than healthy individuals, suggesting that RP24-315D19.10-regulated hnRNPA2B1 may participate in the development and progression of early spontaneous abortion. Our study indicates that RP24-315D19.10 enhances endometrial decidualization in a hnRNPA2B1-dependent manner, providing further insights into this physiological process.
The Phenotype-Genotype Reference Map: Improving biobank data science through replication
Authors: Bastarache Lisa , Delozier Sarah , Pandit Anita , He Jing , Lewis Adam , Annis Aubrey C , LeFaive Jonathon , Denny Joshua C. , Carroll Robert J. , Hughey Jacob J. , Zawistowski Matthew , Peterson Josh F. 
Published: September 2022

AbstractPopulation-scale biobanks linked to electronic health record data provide vast opportunity to extend our knowledge of human genetics. While biobanks have already proven their value to research, data quality remains an important concern. Here we introduce the phenotype-genotype reference map (PGRM), a set of 5,879 genetic associations from 523 GWAS publications that can be used for high-throughput replication experiments in biobank data. We tested the PGRM on five ancestry-specific cohorts drawn from four established, independent biobanks and found evidence of robust replications across a wide array of phenotypes. We defined simple replication measures and show how these can be applied to any EHR-linked biobank to detect data corruption and to empirically assess parameters for phenome-wide studies. Finally, we used the PGRM to determine factors associated with reproducibility of GWAS results.
MRI-based computational model generation for cerebral perfusion simulations in health and ischaemic stroke
Authors: Józsa T. I. , Petr J. , Barkhof F. , Payne S. J. , Mutsaerts H. J. M. M. 
Published: September 2022

AbstractCerebral perfusion models were found to be promising research tools to predict the impact of acute ischaemic stroke and related treatments on cerebral blood flow (CBF) linked to patients’ functional outcome. To provide insights relevant to clinical trials, perfusion simulations need to become suitable for group-level investigations, but computational studies to date have been limited to a few patient-specific cases. This study set out to overcome issues related to automated parameter inference, that restrict the sample size of perfusion simulations, by integrating neuroimaging data. Seventy-five brain models were generated using measurements from a cohort of 75 healthy elderly individuals to model resting-state CBF distributions. Computational perfusion model geometries were adjusted using healthy reference subjects’ T1-weighted MRI. Haemodynamic model parameters were determined from CBF measurements corresponding to arterial spin labelling perfusion MRI. Thereafter, perfusion simulations were conducted for 150 acute ischaemic stroke cases by simulating an occlusion and cessation of blood flow in the left and right middle cerebral arteries. The anatomical (geometrical) fitness of the brain models was evaluated by comparing the simulated grey and white matter (GM and WM) volumes to measurements in healthy reference subjects. Statistically significant, strong positive correlations were found in both cases (GM: Pearson’s r 0.74, P-value< 0.001; WM: Pearson’s r 0.84, P-value< 0.001). Haemodynamic parameter tuning was verified by comparing total volumetric blood flow rate to the brain in reference subjects and simulations resulting in Pearson’s r 0.89, and P-value< 0.001. In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based proxy was 197±25 ml. Computational results showed excellent agreement with anatomical and haemodynamic literature data corresponding to T1-weighted, T2-weighted, and phase-contrast MRI measurements both in healthy scenarios and in acute ischaemic stroke cases. Simulation results represented solely worst-case stroke scenarios with large infarcts because compensatory mechanisms, e.g. collaterals, were neglected. The established computational brain model generation framework provides a foundation for population-level cerebral perfusion simulations and for in silico clinical stroke trials which could assist in medical device and drug development.
Strategies and Techniques for Quality Control and Semantic Enrichment with Multimodal Data: A Case Study in Colorectal Cancer with eHDPrep
Authors: Toner Tom M , Miller Paul , Forster Thorsten , Coleman Helen G , Overton Ian M 
Published: September 2022

AbstractBackgroundIntegration of data from multiple domains can greatly enhance the quality and applicability of knowledge generated in analysis workflows. However, working with health data is challenging, requiring careful preparation in order to support meaningful interpretation and robust results. Ontologies encapsulate relationships between variables that can enrich the semantic content of health datasets to enhance interpretability and inform downstream analyses.FindingsWe developed an R package for electronic Health Data preparation ‘eHDPrep’, demonstrated upon a multi-modal colorectal cancer dataset (n=661 patients, n=155 variables; Colo-661). eHDPrep offers user-friendly methods for quality control, including internal consistency checking and redundancy removal with information-theoretic variable merging. Semantic enrichment functionality is provided, enabling generation of new informative ‘meta-variables’ according to ontological common ancestry between variables, demonstrated with SNOMED CT and the Gene Ontology in the current study. eHDPrep also facilitates numerical encoding, variable extraction from free-text, completeness analysis and user review of modifications to the dataset.ConclusioneHDPrep provides effective tools to assess and enhance data quality, laying the foundation for robust performance and interpretability in downstream analyses. Application to a multi-modal colorectal cancer dataset resulted in improved data quality, structuring, and robust encoding, as well as enhanced semantic information. We make eHDPrep available as an R package from CRAN [[URL will go here]].
Exploring high-quality microbial genomes by assembling short-reads with long-range connectivity
Authors: Zhang Zhenmiao , Xiao Jin , Wang Hongbo , Yang Chao , Huang Yufen , Yue Zhen , Chen Yang , Han Lijuan , Yin Kejing , Lyu Aiping , Fang Xiaodong , Zhang Lu 
Published: September 2022

AbstractDespite long-read sequencing enables to generate complete genomes of unculturable microbes, its high cost hinders its widespread application in large cohorts. An alternative method is to assemble short-reads with long-range connectivity, which can be a cost-effective way to generate high-quality microbial genomes. We developed Pangaea to improve metagenome assembly using short-reads with physical or virtual barcodes. It adopts a deep-learning-based binning algorithm to assemble the co-barcoded reads with similar sequence contexts and abundances to improve assemblies of high- and medium-abundance microbes. Pangaea also leverages a multi-thresholding reassembly strategy to refine assembly for low-abundance microbes. We benchmarked Pangaea with linked-reads and a combination of short- and long-reads from mock communities and human gut metagenomes. Pangaea achieved significantly higher contig continuity as well as more near-complete metagenome-assembled genomes (NCMAGs) than the existing assemblers. Pangaea was also observed to generate three complete and circular NCMAGs on the human gut microbiomes.
Temporal enzymatic treatment to enhance the remodelling of multiple cartilage microtissues into a structurally organised tissue
Authors: Burdis Ross , Gallostra Xavier Barceló , Kelly Daniel J. 
Published: September 2022

AbstractScaffold-free tissue engineering strategies aim to recapitulate key aspects of normal developmental processes as a means of generating highly biomimetic grafts. Cartilage and fibrocartilaginous tissues have successfully been engineered by bringing together large numbers of cells, cellular aggregates or microtissues and allowing them to self-assemble or self-organize into a functional graft. Despite the promise of such approaches, considerable challenges still remain, such as engineering scaled-up tissues with predefined geometries, ensuring robust fusion between adjacent cellular aggregates or microtissues, and directing the (re)modelling of such biological building blocks into a unified scaled-up graft with hierarchical matrix organisation mimetic of the native tissue. In this study, we first demonstrate the benefits of engineering cartilage via the fusion of multiple cartilage microtissues compared to conventional scaffold-free approaches where (millions of) individual cells are allowed to aggregate and generate a cartilaginous graft. Key advantages include the engineering of a tissue with a richer extracellular matrix, a more hyaline-like cartilage phenotype and a final graft which better matched the intended geometry. A major drawback associated with this approach is that individual microtissues did not completely (re)model and remnants of their initial architectures where still evident throughout the macrotissue. In an attempt to address this limitation, the enzyme chondroitinase ABC (cABC) was employed to accelerate structural (re)modelling of the engineered tissue. Temporal enzymatic treatment supported robust fusion between adjacent microtissues, enhanced microtissue (re)modelling and supported the development of a more biomimetic tissue with a zonally organised collagen architecture. Additionally, we observed that cABC treatment modulated matrix composition (rebalancing the collagen:glycosaminoglycans ratio), tissue phenotype, and to a lesser extent, tissue mechanics. Ultimately, this work demonstrates that microtissue self-organisation is an effective method for engineering scaled-up cartilage grafts with a pre-defined geometry and near-native levels of ECM accumulation. Importantly we have demonstrated that key limitations associated with tissue engineering using multiple cellular aggregates, microtissues or organoids can be alleviated by temporal enzymatic treatment during graft development.
Maternal provisioning of an obligate symbiont
Authors: Carrier Tyler J. , Schmittmann Lara , Jung Sabrina , Pita Lucía , Hentschel Ute 
Published: September 2022

ABSTRACTVertical transmission of microbial symbionts is interpreted as all offspring within a clutch being provided a similar number of symbionts irrespective of reproductive output (fecundity). This interpretation, however, stems primarily from oviparous insects and, thus, has yet to consider other major reproductive strategies. We used the viviparous spongeHalichondria paniceaand its obligate symbiont “CandidatusHalichondribacter symbioticus” to test the hypothesis that offspring receive quantitatively similar numbers of its obligate symbiont. This quantitative strategy of vertical transmission was not observed. Instead, we find thatH. paniceahas a maternal pool of ‘Ca. H. symbioticus’ that is partitioned proportionally to reproductive output and allometrically by offspring size. Moreover, ‘Ca. H. symbioticus’ could not be experimentally reduced in larvae by antibiotics, while the total bacterial community could be depleted. The ability to undergo metamorphosis was unaffected by this perturbation. Together, this demonstrates that the obligate symbiont ‘Ca. H. symbioticus’ is maternally provisioned and, thus, provides an additional strategy for how microbes can be vertically transmitted.
Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis
Authors: Nakajima-Takagi Yaeko , Oshima Motohiko , Takano Junichiro , Koide Shuhei , Itokawa Naoki , Uemura Shun , Yamashita Masayuki , Andoh Shohei , Aoyama Kazumasa , Isshiki Yusuke , Shinoda Daisuke , Saraya Atsunori , Arai Fumio , Yamaguchi Kiyoshi , Furukawa Yoichi , Koseki Haruhiko , Ikawa Tomokatsu , Iwama Atsushi 
Published: September 2022

SUMMARYPolycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBPα-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and β-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation.
Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes
Authors: Qi Lu , Lin Shing-Hong , Ma Qiufu 
Published: September 2022

SUMMARYVisceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here we used a focal colorectal distention (fCRD) method to drive visceromotor responses (VMRs) plus affective pain-indicative aversive learning. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion. We next showed that spinal VGLUT3 neurons mediate affective visceral allodynia, whose ablation caused loss of aversion evoked by low-intensity fCRD in mice with gastrointestinal (GI) inflammation or spinal circuit disinhibition. Importantly, these neurons are dispensable for driving VMRs. Anatomically, VGLUT3 neurons send projection to the parabrachial nuclei, whose photoactivation sufficiently generated aversion in mice with GI inflammation. Our studies suggest the presence of different spinal substrates that transmit nociceptive versus affective dimensions of visceral sensory information.
Small RNAs activate Salmonella pathogenicity island 1 by modulating mRNA stability through the hilD mRNA 3′ UTR
Authors: Abdulla Sabrina Z. , Kim Kyungsub , Azam Muhammad S. , Golubeva Yekaterina A. , Cakar Fatih , Slauch James M. , Vanderpool Carin K. 
Published: September 2022

AbstractSalmonella enterica serovar Typhimurium is an enteric pathogen associated with food-borne disease. Salmonella invades the intestinal epithelium using a type three secretion system encoded in Salmonella pathogenicity Island 1 (SPI-1). SPI-1 genes are tightly regulated by a complex feed-forward loop to ensure proper spatial and temporal expression. Most regulatory input is integrated at HilD, through control of hilD mRNA translation or HilD protein activity. The hilD mRNA possesses a 310-nucleotide 3′ untranslated region (UTR) that influences HilD and SPI-1 expression, and this regulation is dependent on Hfq and RNase E, cofactors known to mediate small RNA (sRNA) activities. Thus, we hypothesized that the hilD mRNA 3′ UTR is a target for sRNAs. Here we show that the sRNAs, SdsR and Spot 42 regulate SPI-1 by targeting different regions of the hilD mRNA 3′ UTR. Regulatory activities of these sRNAs depend on Hfq and RNase E, in agreement with previous roles found for both at the hilD 3′ UTR. We show that SdsR and RNase E are responsible for the accumulation of variable fragments of the hilD mRNA 3′ UTR. Collectively, this work suggests that these sRNAs targeting the hilD mRNA 3′ UTR regulate hilD mRNA levels by interfering with RNase E-dependent mRNA degradation. Our work provides novel insights into mechanisms of sRNA regulation at bacterial mRNA 3′ UTRs and adds to our knowledge of post-transcriptional regulation of the SPI-1 complex feed-forward loop.ImportanceSalmonella are prominent food-borne pathogens, infecting millions of people a year. To express virulence genes at the correct time and place in the host, Salmonella uses a complex regulatory network that senses environmental conditions. Known for their role in allowing quick responses to stress and virulence conditions, we investigate the role of small RNAs in facilitating precise expression of these genes. We provide evidence that the 3′ untranslated region of the hilD mRNA, encoding a key virulence regulator, is a target for small RNAs and the ribonuclease RNase E. The small RNAs play a role in stabilizing hilD mRNA to allow proper expression of Salmonella virulence genes in the host.
Pre-existing immunity to influenza viruses through infection and/or vaccination leads to viral mutational signatures associated with unique immune responses during a subsequent infection
Authors: Rioux Melissa L. , Ge Anni , Yourkowski Anthony , Francis Magen E. , McNeil Mara , Selim Alaa , Xue Bei , Darbellay Joseph , Kelvin Alyson A. 
Published: September 2022

AbstractOur biggest challenge to reducing the burden of seasonal influenza is the constant antigen drift of circulating influenza viruses which then evades the protection of pre-existing immunity. Continual viral infection and influenza vaccination creates a layered immune history in people, however, how host preimmunity interacts with an antigenically divergent virus exposure is poorly understood. Here we investigated the influence of host immune histories on influenza viral mutations. Immune backgrounds were devised in mice similar to what is experienced in people: naive; previously infected (A/FM/1/1947); previously vaccinated (Sanofi quadrivalent vaccine); and previously infected and then vaccinated. Mice were challenged with the heterologous H1N1 strain A/Mexico/4108/2009 to assess protection, viral mutation, and host responses in respect to each immune background by RNAseq. Viral sequences were analyzed for antigenic changes using DiscoTope 2.0 and Immune Epitope Database (IEDB) Analysis Resource NetMHCpan EL 4.1 servers. The mock infected-vaccinated group consistently had the greatest number of viral mutations seen across several viral proteins, HA, NA, NP, and PB1 which was associated with strong antiviral responses and moderate T cell and B cell responses. In contrast, the preimmune-vaccinated mice were not associated with variant emergence and the host profiles were characterized by minimal antiviral immunity but strong T cell, B cell, and NK cell responses. This work suggests that the infection and vaccination history of the host dictates the capacity for viral mutation at infection through immune pressure. These results are important for developing next generation vaccination strategies.ImportanceInfluenza is a continual public health problem. Due to constant virus circulation and vaccination efforts, people have complex influenza immune histories which may impact the outcome of future infections and vaccinations. How immune histories influence the emergence of new variants and the immune pressure stimulated at exposure is poorly understood. Our study addressed this knowledge gap by utilizing mice that are preimmune to influenza viruses and analyzing host responses as well as viral mutations associated with changes in antigenicity. Importantly, we found previous vaccination induced immune responses with moderate adaptive immunity and strong antiviral immunity which was associated with increased mutations in the influenza virus. Interestingly, animals that were previously infected with a heterologous virus and also vaccinated had robust adaptive responses with little to no antiviral induction which was associated with no emergence of viral variants. These results are important for the design of next generation influenza vaccines.
High-intensity interval training combining rowing and cycling efficiently improves insulin sensitivity, body composition and VO2max in men with obesity and type 2 diabetes
Authors: Petersen Maria Houborg , de Almeida Martin Eisemann , Wentorf Emil Kleis , Jensen Kurt , Ørtenblad Niels , Højlund Kurt 
Published: September 2022

AbstractAimNon-weight-bearing high-intensity interval training (HIIT) involving several muscle groups may efficiently improve metabolic health in obesity and type 2 diabetes. In a non-randomized intervention study, we examined the effect of a HIIT-protocol, recruiting both lower and upper body muscles, on insulin sensitivity, measures of metabolic health and adherence in obesity and type 2 diabetes.MethodsIn 15 obese men with type 2 diabetes and age-matched obese (n=15) and lean (n=18) glucose-tolerant men, the effects of 8-weeks supervised HIIT combining rowing and cycling were examined by DXA-scan, exercise test and hyperinsulinemic-euglycemic clamp.ResultsAt baseline, insulin-stimulated glucose disposal rate (GDR) was ∼40% reduced in the diabetic vs the non-diabetic groups (allp<0.01). In response to HIIT, insulin-stimulated GDR increased ∼30-40% in all groups (allp<0.01) explained by increased glucose storage. These changes were accompanied by ∼8-15% increases in VO2max, (allp<0.01), decreased fat mass and increased lean body mass in all groups (allp<0.05). There were no correlations between these training adaptations and no group-differences in these responses. HbA1c showed a clinically relevant decrease in men with type 2 diabetes (4±2 mmol/mol;p<0.05). Importantly, adherence was high (>95%) and no injuries were reported.ConclusionsA novel HIIT-protocol recruiting lower and upper body muscles efficiently improves insulin sensitivity, VO2max and body composition with intact responses in men with obesity and type 2 diabetes. The high adherence and lack of injuries show that non-weight-bearing HIIT involving several muscle groups is a promising mode of exercise training in obesity and type 2 diabetes.