bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pax Protein Depletion in Proximal Tubules Triggers Conserved Mechanisms of Resistance to Acute Ischemic Kidney Injury and Prevents Transition to Chronic Kidney Disease
Authors: Beamish Jeffrey A. , Telang Asha C. , McElliott Madison C. , Al-Suraimi Anas , Chowdhury Mahboob , Ference-Salo Jenna T. , Otto Edgar A. , Menon Rajasree , Soofi Abdul , Weinberg Joel M. , Patel Sanjeevkumar R. , Dressler Gregory R. 
Published: October 2023

ABSTRACTAcute kidney injury (AKI) is a common condition that lacks effective treatments. In part this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI. In this report, we examined the role of Pax2 and Pax8 in recovery from ischemic AKI. We found that Pax2 and Pax8 are upregulated after severe AKI and correlate with chronic injury. Surprisingly, we then discovered that proximal-tubule-selective deletion of Pax2 and Pax8 resulted in a less severe chronic injury phenotype. This effect was mediated by protection against the acute insult, similar to preconditioning. Prior to injury, Pax2 and Pax8 mutant mice develop a unique subpopulation of S3 proximal tubule cells that display features usually seen only in acute or chronic injury. The expression signature of these cells was strongly enriched with genes associated with other mechanisms of protection against ischemic AKI including caloric restriction, hypoxic preconditioning, and female sex. Taken together, our results identify a novel role for Pax2 and Pax8 in mature proximal tubules that regulates critical genes and pathways involved in both injury response and protection from ischemic AKI.TRANSLATIONAL STATEMENTIdentifying the molecular and genetic regulators unique to the nephron that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are two homologous nephron-specific transcription factors that are critical for kidney development and physiology. Here we report that proximal-tubule-selective depletion of Pax2 and Pax8 protects against both acute and chronic injury and induces an expression profile in the S3 proximal tubule with common features shared among diverse conditions that protect against ischemia. These findings highlight a new role for Pax proteins as potential therapeutic targets to treat AKI.
SC-Track: a robust cell tracking algorithm for generating accurate single-cell lineages from diverse cell segmentations
Authors: Li Chengxin , Xie Shuang Shuang , Wang Jiaqi , Sharvia Septavera , Chan Kuan Yoow 
Published: October 2023

AbstractComputational analysis of fluorescent timelapse microscopy images at the single-cell level is a powerful approach to study cellular changes that dictate important cell fate decisions. Core to this approach is the need to generate reliable cell segmentations and classifications necessary for accurate quantitative analysis. Deep learning-based convolutional neural networks (CNNs) have emerged as a promising solution to these challenges. However, current CNNs are prone to produce noisy cell segmentations and classifications, which is a significant barrier to constructing accurate single-cell lineages. To address this, we developed a novel algorithm called Single Cell Track (SC-Track), which employs a hierarchical probabilistic cache cascade model based on biological observations of cell division and movement dynamics. Our results show that SC-Track performs better than a panel of publicly available cell trackers on a diverse set of cell segmentation types. This cell-tracking performance was achieved without any parameter adjustments, making SC-Track an excellent generalised algorithm that can maintain robust cell-tracking performance in varying cell segmentation qualities, cell morphological appearances and imaging conditions. Furthermore, SC-Track is equipped with a cell class correction function to improve the accuracy of cell classifications in multi-class cell segmentation time series. These features together make SC-Track a robust cell-tracking algorithm that works well with noisy cell instance segmentation and classification predictions from CNNs to generate accurate single-cell lineages and classifications.
Towards quantitative DNA Metabarcoding: A method to overcome PCR amplification bias
Authors: Moinard Sylvain , Piau Didier , Laporte Frédéric , Rioux Delphine , Taberlet Pierre , Gonindard-Melodelima Christelle , Coissac Eric 
Published: October 2023

AbstractMetabarcoding analyses have recently undergone significant development due to the power of this technique in biodiversity monitoring. However, it is still difficult to draw accurate quantitative conclusions about the ecosystems studied, mainly because of biases inherent in the environmental DNA or introduced during the experimental process. These biases alter the relationship between the amount of DNA observed and the biomass or number of individuals of the species detected. Two of the biases inherent in metabarcoding have been measured: the ratio between total DNA and target DNA concentrations, and the PCR amplification bias. A method for their correction is proposed. All experimental tests were performed on mock alpine plant communities using the markerSper01, which is expected to have low amplification bias due to its highly conserved priming sites. Our approach combines standard quantitative PCR techniques (qPCR and digital droplet PCR) with a realistic stochastic model of PCR dynamics that accounts for PCR saturation. The model was used to estimate PCR efficiencies for each species and to infer the true species proportions of the mock communities from the read relative frequencies. The corrections are easy to implement and can be applied to previously generated DNA metabarcoding data. This work demonstrates the relative importance of the two biases considered and is an open door to quantitative metabarcoding data, although many other biases remain to be considered.
Prognostic implications and biological roles of EMT-related lncRNAs in lung squamous cell carcinoma: an in-depth analysis utilizing a novel prognostic signature and classification system
Authors: Zhang Jinming , Zheng Baihong , Zhang Xiuying , Liu Ying , Guo Ying , Zhao Jia , Liu Jiamei , Xue Hui 
Published: October 2023

AbstractBackgroundLung squamous cell carcinoma (LUSC) represents a major subtype of non-small cell lung cancer (NSCLC), a leading contributor to cancer-related mortality. Epithelial-mesenchymal transition (EMT)-associated genes have been implicated in poor survival and metastatic gene expression in LUSC. Long non-coding RNAs (lncRNAs) are known to facilitate tumor progression and metastasis via EMT regulation. However, the prognostic significance and biological functions of EMT-associated lncRNAs in LUSC remain to be elucidated.MethodsIn this study, we aimed to develop an EMT-related lncRNA prognostic signature (EMT-LPS) utilizing RNA transcription data from LUSC patients in The Cancer Genome Atlas (TCGA) database, along with corresponding clinical characteristics. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and Cox regression were employed to validate and assess the model. Furthermore, we confirmed the independent prognostic value of key genes in EMT-LPS using Gene Expression Profiling Interactive Analysis (GEPIA). Additionally, we proposed a novel LUSC classification system based on EMT-related lncRNA expression patterns, evaluating the prognostic profile, tumor microenvironment, and immunotherapy sensitivity of each subtype.ResultsA prognostic signature comprising twelve genes was constructed, and patients were stratified into high and low-risk groups according to their risk scores. Cox regression analysis revealed that the risk score served as an independent prognostic factor. A nomogram was generated to predict LUSC patient survival rates. Distinct subtypes exhibited varying tumor purity, immunogenicity, and immunotherapy drug sensitivity.ConclusionsOur findings underscore the relevance of EMT-related lncRNAs in LUSC and their potential utility in guiding immunotherapy strategies. The EMT-LPS and novel LUSC typing scheme provide a new perspective for understanding the biological functions and prognostic role of EMT-related lncRNAs in LUSC.
Palatal segment contributions to midfacial anterior-posterior growth
Authors: Welsh Ian C. , Feiler Maria E. , Lipman Danika , Mormile Isabel , Hansen Karissa , Percival Christopher J. 
Published: October 2023

AbstractAnterior-posterior (A-P) elongation of the palate is a critical aspect of integrated midfacial morphogenesis. Reciprocal epithelial-mesenchymal interactions drive secondary palate elongation that is coupled to the periodic formation of signaling centers within the rugae growth zone (RGZ). However, the relationship between RGZ-driven morphogenetic processes, the differentiative dynamics of underlying palatal bone mesenchymal precursors, and the segmental organization of the upper jaw has remained enigmatic. A detailed ontogenetic study of these relationships is important because palatal segment growth is a critical aspect of normal midfacial growth, can produce dysmorphology when altered, and is a likely basis for evolutionary differences in upper jaw morphology. We completed a combined whole mount gene expression and morphometric analysis of normal murine palatal segment growth dynamics and resulting upper jaw morphology. Our results demonstrated that the first formed palatal ruga (ruga 1), found just posterior to the RGZ, maintained an association with important nasal, neurovascular and palatal structures throughout early midfacial development. This suggested that these features are positioned at a proximal source of embryonic midfacial directional growth. Our detailed characterization of midfacial morphogenesis revealed a one-to-one relationship between palatal segments and upper jaw bones during the earliest stages of palatal elongation. Growth of the maxillary anlage within the anterior secondary palate is uniquely coupled to RGZ-driven morphogenesis. This may help drive the unequaled proportional elongation of the anterior secondary palate segment prior to palatal shelf fusion. Our results also demonstrated that the future maxillary-palatine suture, approximated by the position of ruga 1 and consistently associated with the palatine anlage, formed predominantly via the posterior differentiation of the maxilla within the expanding anterior secondary palate. Our ontogenetic analysis provides a novel and detailed picture of the earliest spatiotemporal dynamics of intramembranous midfacial skeletal specification and differentiation within the context of the surrounding palatal segment A-P elongation and associated rugae formation.
CRWN nuclear lamina components maintain the H3K27me3 landscape and promote successful reproduction in Arabidopsis
Authors: Choi Junsik , Gehring Mary 
Published: October 2023

AbstractThe nuclear lamina, a sub-nuclear protein matrix, maintains nuclear structure and genome function. Here, we investigate the role of Arabidopsis lamin analogs CROWDED NUCLEIs during gametophyte and seed development. We observed defects incrwnmutant seeds, including seed abortion and reduced germination rate. Quadruplecrwnnull genotypes were rarely transmitted through gametophytes. We focused on thecrwn1 crwn2(crwn1/2) endosperm, which exhibited enlarged chalazal cysts and increased expression of stress-related genes and the MADS-box transcription factorPHERES1and its targets. Previously, it was shown thatPHERES1is regulated by H3K27me3 and that CRWN1 interacts with the PRC2 interactor PWO1. Thus, we tested whethercrwn1/2alters H3K27me3 patterns. We observed a mild loss of H3K27me3 at several hundred loci, which differed between endosperm and leaves. These data indicate that CRWNs are necessary to maintain the H3K27me3 landscape, with tissue-specific chromatin and transcriptional consequences.
Voluntary alcohol consumption during distinct phases of adolescence differentially alters adult fear acquisition, extinction and renewal in male and female rats
Authors: Grizzell J Alex , Vanbaelinghem Maryam , Westerman Jessica , Saddoris Michael P 
Published: October 2023

AbstractAlcohol use during adolescence coincides with elevated risks of stress-related impairment in adults, particularly via disrupted developmental trajectories of vulnerable corticolimbic and mesolimbic systems involved in fear processing. Prior work has investigated the impact of binge-like alcohol consumption on adult fear and stress, but less is known about whether voluntarily consumed alcohol imparts differential effects based on adolescence phases and biological sex. Here, adolescent male and female Long Evans rats were granted daily access to alcohol (15%) during either early (Early-EtOH; P25-45) or late adolescence (Late-EtOH; P45-55) using a modified drinking-in-the-dark design. Upon adulthood (P75-80), rats were exposed to a three-context (ABC) fear renewal procedure. We found that male and female Early-EtOH rats showed faster acquisition of fear but less freezing during early phases of extinction and throughout fear renewal. In the extinction period specifically, Early-EtOH rats showed normal levels of freezing in the presence of fear-associated cues, but abnormally low freezing immediately after cue offset, suggesting a key disruption in contextual processing and/or novelty seeking brought by early adolescent binge consumption. While the effects of alcohol were most pronounced in the Early-EtOH rats (particularly in females), Late-EtOH rats displayed some changes in fear behavior including slower fear acquisition, faster extinction, and reduced renewal compared with controls, but primarily in males. Our results suggest that early adolescence in males and females and, to a lesser extent, late adolescence in males is a particularly vulnerable period wherein alcohol use can promote stress-related dysfunction in adulthood. Furthermore, our results provide multiple bases for future research focused on developmental correlates of alcohol mediated disruption in the brain.
Whole genome assembly and annotation of the clover root weevil (Sitona obsoletus) using a combination of Illumina, 10X Genomics and MinION sequencing
Authors: Katuwal Mandira , Phillips Craig B. , Gemmell Neil J. , Dowle Eddy 
Published: October 2023

AbstractWeevils are a highly diversified taxon, comprising about 70,000 described species that include many agricultural pests, biological control agents, and nutrient recyclers. Despite their importance and vast diversity, the number of sequenced genomes for the weevil family is still low (n=15). Here, we present a high-quality and contiguous genome assembly ofSitona obsoletus(Coleoptera: Curculionidae: Entiminae), a widespread invasive forage pest that infests clover species (Trifoliumspp.) worldwide. We sequenced, assembled, and annotated theS. obsoletusgenome using a hybrid approach that employed Nanopore long reads, 10X Chromium linked reads, Illumina short reads for assembly, and mRNA short read sequencing of various developmental stages for annotation. Our final annotated genome has a size of 1.2 Gb, with an N50 length of 313.85 kb. Benchmarking analyses against conserved single-copy Orthologs (BUSCO) found that over 94% of the genes were complete from each of the three BUSCO databases (Eukaryota, Insecta, and Arthropoda). A total of 9,777 protein-coding genes were annotated using the MAKER2 pipeline, of which 65% were functionally annotated. The annotated repeat elements make up 84.26% of the genome. The high-quality annotated genome of the weevil will facilitate a wide range of genetic, genomic, and phylogenetic studies on invasive weevils, as well as other weevil species in the subfamily Entiminae.
Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma
Authors: Prakash Ajay , Rubin Nathan , Staley Christopher , Onyeaghala Guillaume , Wen Ya-Feng , Shaukat Aasma , Milne Ginger , Straka Robert J. , Church Timothy R. , Prizment Anna 
Published: October 2023

ABSTRACTGinger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the generaAkkermansia(p<0.001),Bacteroides(p=0.018), andRuminococcus(p=0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances ofAkkermansiaandBacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.
The role of cytomegalovirus in prostate cancer incidence and mortality
Authors: Classon Johanna , Britten Abigail , Alkass Kanar , Druid Henrik , Brenner Nicole , Waterboer Tim , Wareham Nicholas J , Gkrania-Klotsas Effrossyni , Frisén Jonas 
Published: October 2023

ABSTRACTProstate cancer is one of the most common cancers in men with over 350 000 prostate cancer deaths reported worldwide every year. Current risk stratification models are insufficient to predict prostate cancer and prostate cancer death. New biomarkers are needed to identify those at increased risk of lethal prostate cancer. Cytomegalovirus (CMV) infection is common in the healthy prostate epithelium and promotes cell proliferation and viability in prostate cancer. Analyzing matched serum and tissue samples from post-mortem donors (n=41) and prostate cancer patients (n=40), we report that CMV seropositivity predicts high CMV abundance in prostate tissue. We studied if CMV seropositive men had increased prostate cancer incidence and cancer mortality in the European Prospective Investigation of Cancer (EPIC)–Norfolk population-based cohort study. CMV IgG serostatus was determined between 1993 and 2000 in 7,655 men aged 40-81 years, of which 57% were CMV seropositive. Study participants were followed for 18±6.0 years (mean±SD). We used Cox proportional hazard models, adjusted for age and potential confounders to estimate hazard ratios (HR) with 95% confidence intervals (CI). CMV serostatus was not associated with prostate cancer incidence (adjusted HR 1.03, 95% CI 0.89-1.19, p=0.687, 138,652 person-years). However, among prostate cancer patients, CMV seropositivity was associated with increased risk of prostate cancer-associated mortality (adjusted HR 2.26, CI 95% 1.02-4.99, p=0.044, 4639 person-years), with 25% of seropositive and 18% of seronegative prostate cancer patients dying from their disease during follow up. These results show that CMV seropositivity is associated with increased risk of prostate cancer death and suggest that CMV infection may contribute to prostate cancer lethality.
Development and validation of automated methods for COVID-19 PCR MasterMix preparation
Authors: Fedele Giorgio , Hill Graham , Sweetford Amelia , Lee Suki , Yau Bobby , Caputo Domenico R. , Grovewood Denise , Dahir Rowda , Ruiz-Dana Paula Esquivias , Wisniewska Anika , Di Biase Anna , Gibson Miles , Percival Benita , Grujic Stefan , Fraser Donald P. 
Published: October 2023

AbstractPolymerase Chain Reaction (PCR)-based assays were widely deployed during the SARS-CoV-2 pandemic for population-scale testing. High-throughput molecular diagnostic labora-tories required a high degree of process automation to cope with huge testing demand, fast turn-around times and quality requirements. However, the critical step of preparing a PCR MasterMix has often been neglected by process developers and optimisers, and is largely dependent upon operator skill for the manual pipetting of reagents to construct the PCR MasterMix. Dependence on manual procedures introduces variation, inconsistency, wastage and potentially risks data integrity. To address this issue, we developed a liquid-handler based solution for automated, traceable and compliant PCR MasterMix preparation. Here, we show that a fully automated PCR MasterMix protocol can substitute manual pipetting, without affecting clinical calling, accuracy or precision. Ultimately, this method reduced cost-per-test at a high-throughput laboratory by eliminating operator-induced wastage while improving the quality of results.
Humoral and cellular immune responses following BNT162b2 XBB.1.5 vaccination
Authors: Stankov Metodi V. , Hoffmann Markus , Jauregui Rodrigo Gutierrez , Cossmann Anne , Ramos Gema Morillas , Graalmann Theresa , Friedrichsen Michaela , Ravens Inga , Ilievska Tamara , Ristenpart Jasmin , Schimrock Anja , Willenzon Stefanie , Ahrenstorf Gerrit , Witte Torsten , Förster Reinhold , Kempf Amy , Pöhlmann Stefan , Hammerschmidt Swantje I. , Alexandra Dopfer-Jablonka , Behrens Georg M. N. 
Published: October 2023

AbstractSARS-CoV-2 Omicron XBB subvariants efficiently evade immunity from prior infection or vaccination, requiring vaccine adaptation. Here, we analyzed immunogenicity of an adapted vaccine, BNT162b2 Omicron XBB.1.5, which is currently used for booster vaccination. Booster vaccination significantly increased anti-Spike IgG, accompanied by expansion of cross-reactive memory B cells recognizing Wuhan and Omicron XBB.1.5 spike variants. Geometric mean neutralizing titers against XBB.1.5, XBB.1.16 and XBB.2.3, as well as cross-reactive responses against EG.5.1 and BA.2.86 increased significantly relative to pre-booster titers. Finally, the number of Wuhan and XBB.1.5 spike reactive IFN-γ-producing T cells significantly increased after booster vaccination. In summary, BNT162b2 Omicron XBB.1.5 vaccination resulted in potent neutralizing antibody responses against Omicron XBB variants, including the recent Omicron variants EG.5.1 (Eris) and BA.2.86 (Pirola), as well as XBB.1.5 reactive T cell responses, suggesting that booster vaccination will augment protection against these emerging variants.