bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer
Authors: Yue Fei , Ku Amy T. , Stevens Payton D. , Michalski Megan N. , Jiang Weiyu , Tu Jianghua , Shi Zhongcheng , Dou Yongchao , Wang Yi , Feng Xin-Hua , Hostetter Galen , Wu Xiangwei , Huang Shixia , Shroyer Noah F. , Zhang Bing , Williams Bart O. , Liu Qingyun , Lin Xia , Li Yi 
Published: January 2024

AbstractZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated withZNRF3/RNF43mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression ofZNRF3reduces EGFR levels and suppresses cancer cell growthin vitroandin vivo, whereas knockout ofZNRF3/RNF43stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data highlight ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptors, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.
TCR-engineered T-cells directed against Ropporin-1 constitute a safe and effective treatment for triple-negative breast cancer in near-clinical models
Authors: Kortleve Dian , Hammerl Dora , Brakel Mandy v , Wijers Rebecca , Roelofs Daphne , Kroese Kim , Timmermans Mieke , Liao Chen-Yi , Trapman-Jansen Anita , Foekens Renée , Michaux Justine , de Beijer Monique , Buschow Sonja I. , Demmers Jeroen A.A. , Kok Marleen , Danen Erik H.J. , Bassani-Sternberg Michal , Martens John W. , Abbott Rachel J.M. , Debets Reno 
Published: January 2024

AbstractTriple-negative breast cancer (TNBC) shows an urgent need for new therapies. We discovered Ropporin-1 (ROPN1) as a target to treat TNBC with T-cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues. HLA-A2-binding peptides were detected via immunopeptidomics and predictions and used to retrieve T-cell receptors (TCRs) from naïve repertoires. Following gene introduction into T-cells and stringent selection, we retrieved a highly specific TCR directed against the epitope FLYTYIAKV that did not recognize non-cognate epitopes from alternative source proteins. Notably, this TCR mediated killing of three-dimensional tumoroidsin vitroand tumor cellsin vivoand outperformed standard-of-care drugs. Finally, the T-cell product expressing this TCR and manufactured using a clinical protocol fulfilled standard safety and efficacy assays. Collectively, we have identified and preclinically validated ROPN1 as a target and anti-ROPN1 TCR T-cells as a treatment for the vast majority of TNBC patients.
Unraveling Glioblastoma Heterogeneity: Introducing SP2G Method for Identifying Invasive Sub-Populations
Authors: Crestani Michele , Kakogiannos Nikolaos , Iannelli Fabio , Dini Tania , Maderna Claudio , Giannotta Monica , Pelicci Giuliana , Maiuri Paolo , Monzo Pascale , Gauthier Nils C. 
Published: January 2024

AbstractGlioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, we linked glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry. We now introduce SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient-derived glioblastoma cells and rapidly pinpoint the most invasive sub-populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by our semi-automated, open-source, Fiji macro suite that characterizes migration modes accurately. With SP2G, we could reveal intra-patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. Thus, our system presents a versatile and potentially pan-cancer workflow to detect diverse invasive tumor sub-populations in patient-derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level.TeaserCracking the inter and intra-patient diversity in Glioblastoma migration profiles
Analysis of a diverse wheat germplasm panel reveals a highly diverse introgression landscape and provides evidence for inter-homoeolog chromosomal recombination
Authors: Heuberger Matthias , Bernasconi Zoe , Jung Esther , Herren Gerhard , Widrig Victoria , Keller Beat , Sánchez-Martín Javier , Wicker Thomas 
Published: January 2024

AbstractAgriculturally important genes are often introgressed into crops from closely related donor species or landraces. The gene pool of hexaploid bread wheat (Triticum aestivum)is known to contain numerous such “alien” introgressions. Recently established high-quality reference genome sequences allow prediction of the size, frequency, and identity of introgressed chromosome regions. Here, we characterise chromosomal introgressions in bread wheat using exome capture data from the WHEALBI collection. We identified 26,664 putative introgression segments of at least 2 Mb across 434 wheat accessions. Detailed study of the most frequent introgressions identifiedT. timopheviior its close relatives as a frequent donor species. Importantly, 118 introgressions of at least 10 Mb were exclusive to single wheat accessions, revealing that large populations need to be studied to assess the total diversity of the wheat pangenome. In one case, a 14 Mb introgression in chromosome 7D, exclusive to cultivar Pamukale, was shown by QTL mapping to harbor a recessive powdery mildew resistance gene. We identified multiple events where distal chromosomal segments of one subgenome were duplicated in the genome and replaced the homoeologous segment in another subgenome. We propose that these examples are the results of inter-homoeolog recombination. Our study produced an extensive catalogue of the wheat introgression landscape, providing a resource for wheat breeding. Of note, the finding that the wheat gene pool contains numerous rare, but potentially important introgressions and chromosomal rearrangements has implications for future breeding.Key messageThis study highlights the potential of rare introgressions, as demonstrated by a major QTL for powdery mildew resistance on chromosome 7D. It further shows evidence for inter-homoeolog recombination in wheat.
Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation
Authors: Miao Yue , Du Yongtao , Wang Baolei , Liang Jingjing , Liang Yu , Dang Song , Liu Jiahao , Li Dong , He Kangmin , Ding Mei 
Published: January 2024

AbstractThe spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5. The recruitment of USP8 dissociates Rabex5 from early endosomes (EEs) and meanwhile promotes the recruitment of the Rab7 GEF SAND-1/Mon1. In USP8-deficient cells, the level of active Rab5 is increased, while the Rab7 signal is decreased. As a result, enlarged EEs with abundant intraluminal vesicles accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation.
Ability of mycobacterial pathogens to establish a persistent infection is lost by deletion of a single gene,rel, regulator of the stringent response
Authors: Mahmoud Asmaa H. , Abdellrazeq Gaber S. , Fry Lindsay M. , Schneider David A. , Attreed Sarah , Burton Leeanna , Sangewar Neha , Mwangi Waithaka , deSouza Cleverson , Hulubei Victoria , Davis William C. , Park Kun Taek 
Published: January 2024

AbstractStudies in a mouse model revealedMycobacterium tuberculosis(Mtb) with a deletion ofrel, regulator of the stringent response, could not establish a persistent infection. Studies in cattle with aMycobacterium. a. paratuberculosis reldeletion mutant revealed inability to establish a persistent infection was associated with development of CD8 cytotoxic T cells (CTL) that kill intracellular bacteria. Further comparative studies ex vivo withMbvCalmette-Guérin (BCG) and a BCGreldeletion mutant revealed no clear difference in development of CTL in vitro. As reported, a study of the recall response was conducted with cattle vaccinated with either BCG or with BCGrel,to determine if information could be obtained that would show how gene products under control ofrelinterfere with the CTL response to mycobacterial pathogens in vivo. The study revealed the CTL response elicited by vaccination with BCG was impaired, in comparison with the response elicited by BCGrel. Comparative analysis of the recall response ex vivo revealed the functional impairment was not associated with the timing of appearance of the recall response, expression of IFN-γ, TNF-α, IL-17, or IL-22, or molecules that mediate intracellular killing. Further studies are needed to determine how CD8 CTL functional activity is modulated in vivo by gene products regulated byrel.
DNA microbeads for spatio-temporally controlled morphogen release within organoids
Authors: Afting Cassian , Walther Tobias , Wittbrodt Joachim , Göpfrich Kerstin 
Published: January 2024

AbstractOrganoids have proven to be powerfulin vitromodel systems that mimic features of the corresponding tissuein vivo. However, across tissue types and species, organoids still often fail to reach full maturity and function, because biochemical cues cannot be provided from within the organoid to guide their development. The establishment of such tools has been identified as a major goal of the field. Here, we introduce DNA microbeads as a novel tool for implementing spatio-temporally controlled morphogen gradients inside of organoids at any point in their life cycle. The DNA microbeads are formed in a simple one-pot process, they can be stored for a year and their viscoelastic behavior and surface modification is tunable to mimic the corresponding tissue. Employing medaka retinal organoids and early embryos, we show that DNA microbeads can be integrated into embryos and organoids by microinjection and erased in a non-invasive manner with light. Coupling a recombinant surrogate Wnt to the DNA microbeads we demonstrate the spatio-temporally controlled release of the morphogen from the microinjection site, which leads to the formation of retinal pigmented epithelium while maintaining neuroretinal ganglion cells. We were thus able to bioengineer retinal organoids to more closely mirror the cell type diversity ofin vivoretinas. The DNA microbead technology can easily be adapted to other organoid applications for improved tissue mimicry.
Characterization of the growth promotion and defense enhancement of soybean plants driven by seed treatment of multiple soybean-associated beneficial bacteria
Authors: Calderon Rosalie B. , Ontoy John Christian , Barpharga Inderjit , Ham Jong Hyun 
Published: January 2024

AbstractWe screened soybean-associated bacterial strains from soybean fields in Louisiana, USA, based on various biological activities beneficial for soybean growth and health. Furthermore, we constructed sets of synthetic bacterial community (SBC) containing multiple strains of soybean-associated beneficial bacteria (SABB) having different types of beneficial activities and tested their effects of seed treatment on soybean growth and disease resistance. We found that all three sets of SBC (i.e., Set-1, Set-2, and Set-3) tested promoted soybean growth and yield significantly through seed treatment, showing better performance than the most effective SABB strainPseudomonas putidaSABB7 alone and the commercial seed-treating product included for comparison. Our analysis of soybean microbiomes in the root endosphere and rhizosphere based on 16S rDNA sequence profiles revealed thatBradyrhizobium elkanii, a symbiotic bacterium of soybean, was enriched in both compartments by seed treatment with Set-2 or Set-m4, which were the best-performing bacterial mixture among the three SABB sets and the most effective subset of Set-2, respectively. In addition, the soybean gene expression profile determined by RNA-seq revealed that seed treatment with Set-2 or Set-m4 made soybean plants grown from the treated-seeds induce a higher level of defense-related genes upon infection by the fungal pathogenRhizoctonia solanicompared to those from untreated seeds. These experimental results strongly suggest that the beneficial effects of the bacterial mixtures on plant growth and defense through seed treatment are largely mediated by the change of soybean-associated microbiomes that enriches beneficial components such asB. elkaniiand the defense-priming effect that induces robust defense responses upon pathogen infection. This study provides a valuable insight into the development of innovative and sustainable management strategies through seed treatment of beneficial microbes in a form of SBC for soybean and further other major crops.Abstract Figure
Taxonomy and phylogeny of the family Suberitidae (Porifera: Demospongiae) in California
Authors: Turner Thomas L. , Rouse Greg W. , Weigel Brooke L. , Janusson Carly , Lemay Matthew A. , Thacker Robert W. 
Published: January 2024

AbstractThis study presents a comprehensive taxonomic revision of the family Suberitidae (Porifera: Demospongiae) for California, USA. We include the three species previously known from the region, document two additional species previously known from other regions, and formally describe four new species asPseudosuberites latkesp. nov.,Suberites californianasp. nov.,Suberites kumeyaaysp. nov., andSuberites agaricussp. nov. Multi-locus DNA sequence data is presented for seven of the nine species, and was combined with all publicly available data to produce the most comprehensive global phylogeny for the family to date. By integrating morphological and genetic data, we show that morphological characters may be sufficient for regional species identification but are likely inadequate for global classification into genera that reflect the evolutionary history of the family. We therefore propose that DNA sequencing is a critical component to support future taxonomic revisions.
A highly contiguous genome assembly for the Yellow Warbler (Setophaga petechia)
Authors: Tsai Whitney L. E. , Escalona Merly , Garrett Kimball L. , Terrill Ryan S. , Sahasrabudhe Ruta , Nguyen Oanh , Beraut Eric , Seligmann William , Fairbairn Colin W. , Harrigan Ryan J. , McCormack John E. , Alfaro Michael E. , Smith Thomas B. , Bay Rachael A. 
Published: January 2024

AbstractThe Yellow Warbler (Setophaga petechia) is a small songbird in the New World Warbler family (Parulidae) that exhibits phenotypic and ecological differences across a widespread distribution and is important to California’s riparian habitat conservation. Here, we present a high-qualityde novogenome assembly of a vouchered female Yellow Warbler from southern California. Using HiFi long-read and Omni-C proximity sequencing technologies, we generated a 1.22 Gb assembly including 687 scaffolds with a contig N50 of 6.80 Mb, scaffold N50 of 21.18 Mb, and a BUSCO completeness score of 96.0%. This highly contiguous genome assembly provides an essential resource for understanding the history of gene flow, divergence, and local adaptation and can inform conservation management of this charismatic bird species.
Impacts of increasing isolation and environmental variation on Florida Scrub-Jay demography
Authors: Summers Jeremy , Cosgrove Elissa J. , Bowman Reed , Fitzpatrick John W. , Chen Nancy 
Published: January 2024

AbstractIsolation caused by anthropogenic habitat fragmentation can destabilize populations. Populations relying on the inflow of immigrants can face reduced fitness due to inbreeding depression as fewer new individuals arrive. Empirical studies of the demographic consequences of isolation are critical to understand how populations persist through changing conditions. We used a 34-year demographic and environmental dataset from a population of cooperatively-breeding Florida Scrub-Jays (Aphelocoma coerulescens) to create mechanistic models linking environmental and demographic factors to population growth rates. We found that the population has not declined despite both declining immigration and increasing inbreeding, owing to a coinciding response in breeder survival. We find evidence of density-dependent immigration, breeder survival, and fecundity, indicating that interactions between vital rates and local density play a role in buffering the population against change. Our study elucidates the impacts of isolation on demography and how long-term stability is maintained via demographic responses.
Disruption inCYLC1leads to acrosome detachment, sperm head deformity, and male in/subfertility in humans and mice
Authors: Jin Hui-Juan , Fan Yong , Yang Xiao-Yu , Dong Yue , Zhang Xiao-Zhen , Geng Xin-Yan , Yan Zheng , Wu Ling , Ma Meng , Li Bin , Lyu Qi-Feng , Pan Yun , Liu Ming-Xi , Kuang Yan-Ping , Chen Su-Ren 
Published: January 2024

AbstractThe perinuclear theca (PT) is a dense cytoplasmic web encapsulating the sperm nucleus. The physiological roles of PT in sperm biology and the clinical relevance of variants of PT proteins to male infertility are still largely unknown. We reveal that cylicin-1, a major constituent of the PT, is vital for male fertility in both mice and humans. Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus. Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an ‘IAM-cylicins-NE’ sandwich structure, anchoring the acrosome to the nucleus. WES of more than 500 Chinese infertile men with sperm head deformities was performed and aCYLC1variant was identified in 19 patients.Cylc1-mutant mice carrying this variant also exhibited sperm acrosome/head deformities and reduced fertility, indicating that thisCYLC1variant most likely affects human male reproduction. Furthermore, the outcomes of assisted reproduction were reported for patients harbouring theCYLC1variant. Our findings demonstrate a critical role of cylicin-1 in the sperm acrosome-nucleus connection and suggestCYLC1variants as potential risk factors for human male fertility.
Germline HLA-DQ genotype influences response to CAR T-cell therapy in patients with large B-cell lymphoma
Authors: Le Mene Melchior , Allain Vincent , Villemonteix Juliette , Cuffel Alexis , Taupin Jean-Luc , di Blasi Roberta , Thieblemont Catherine , Caillat-Zucman Sophie 
Published: January 2024

AbstractCD19-directed chimeric antigen receptor (CAR) T cells have greatly improved the prognosis of relapsed/refractory large B-cell lymphoma (rrLBCL), yet treatment failure occurs in more than half of patients, usually in the first 3 months after treatment. While they primarily act through CAR-dependent, HLA-independent recognition of tumor targets, CAR-T cells may also indirectly contribute to long-term tumor immunosurveillance by stimulating endogenous immunity. We hypothesized that HLA diversity, measured by the HLA evolutionary divergence (HED) metric which reflects the breadth of the immunopeptidome presented to host T cells, could influence antitumor response after CAR T-cell therapy, as seen after immune chekpoint inhibitor treatment. We studied 127 rrLBCL patients treated with commercial CAR-T cells in our center, of whom 50 % achieved durable response. We observed no impact of diversity at any HLA locus, except for HED-DQA1 that was surprisingly negatively associated with response. Analysis of the distribution of HLA-DQ alleles according to clustering of HED values pointed to the DQ1/DQ1 genotype as an independent predictor of durable response and lower incidence of relapse/progression. These findings highlight the unsuspected role of germline HLA-DQ molecules in the response to CAR-T cells and suggest an important contribution of cross-talk between CAR-T cells and endogenous immune cells.Key PointsGermline HLA-DQ genotype is an independent predictor of durable response and lower incidence of relapse/progression after CAR T-cell therapy in rrLBCLHLA-DQ1/DQ1 genotype could influence the host immune response after CAR T-cell therapy and increase the chances of a durable response
Development and validation of a realistic type III esophageal atresia simulator for the training of pediatric surgeons
Authors: Montero Javier Arredondo , Pérez Riveros Blanca Paola , Bueso Asfura Oscar Emilio , Martín-Calvo Nerea , Pueyo Francisco Javier , López de Aguileta Castaño Nicolás 
Published: January 2024

ABSTRACTBackgroundThe technical complexity and limited casuistry of neonatal surgical pathology limit the possibilities of developing the necessary technical competencies by specialists in training. Esophageal atresia constitutes the paradigm of this problem. The use of 3D models for training is a promising line of research, although the literature is limited.MethodsWe conceptualized, designed, and produced an anatomically realistic model for the open correction of type III oesophageal atresia. We validated it with two groups of participants (experts and non-experts) through face, construct, and content validity questionnaires.ResultsThe model was validated by 9 experts and 9 non-experts. The mean procedure time for the experts and non-experts groups was 34.0 and 38.4 minutes respectively. Two non-experts did not complete the procedure at the designed time (45 minutes). Regarding the face validity questionnaire, the mean rating of the model was 3.2 out of 4. Regarding the construct validity, we found statistically significant differences between groups for the equidistance between sutures, 100% correct in the expert group vs. 42.9% correct in the non-expert group (p=0.02), and for the item “Confirms that tracheoesophageal fistula closure is watertight before continuing the procedure”, correctly assessed by 66.7% of the experts vs. by 11.1% of non-experts (p=0.05). Concerning content validity, the mean score was 3.3 out of 4 for the experts and 3.3 out of 4 for the non-experts (p=0.32).ConclusionsThe present model is a cost-effective, simple to produce, and validated option for the training of open correction of type III oesophageal atresia. Future studies with larger sample sizes and blinded validators are needed before drawing definitive conclusions.FundingNone