bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of wheat alpha-gliadins from chromosome 6D improves gluten strength and reduces immunodominant celiac disease epitopes
Authors: Rottersman Maria G. , Zhang Wenjun , Zhang Junli , Grigorian Gabriela , Burguener German , Carter Claudia , Vang Teng , Hegarty Joshua , Zhang Xiaoqin , Dubcovsky Jorge 
Published: July 2024

AbstractWheat gliadins and glutenins confer valuable end-use characteristics but include amino acid sequences (epitopes) that can elicit celiac disease (CeD) in genetically predisposed individuals. The onset of CeD in these individuals is affected by the amount and duration of the exposure to immunogenic epitopes. Therefore, a reduction of epitopes that result in high immune responses in the majority of CeD patients (immunodominant epitopes) can reduce the incidence of CeD at a population level. We identified deletions encompassing the α-gliadins at the three wheat genomes, designated hereafter asΔgli-A2(PI 704906),Δgli-B2(PI 704907), andΔgli-D2(PI 704908). TheΔgli-D2deletion, which eliminates major immunodominant epitopes, significantly increases gluten strength, improves breadmaking quality, and has no negative effects on grain yield or grain protein content. By contrast,Δgli-A2andΔgli-B2showed limited effects on breadmaking quality. The stronger effect of theΔgli-D2deletion on gluten strength is associated with the presence of α-gliadins with seven cysteines inGLI-D2that are absent inGLI-A2andGLI-B2loci, which all have α-gliadins with six cysteines. We show that α-gliadins with seven cysteines are incorporated into the gluten polymer, where they likely function as chain-terminators limiting the expansion of the gluten polymer and reducing its strength. In summary, the publicly availableΔgli-D2deletion developed in this study can be used to simultaneously improve wheat gluten strength and reduce immunodominant CeD epitopes.
Advances in Estimating Level-1 Phylogenetic Networks from Unrooted SNPs
Authors: Warnow Tandy , Tabatabaee Yasamin , Evans Steven N. 
Published: July 2024

AbstractWe address the problem of how to estimate a phylogenetic network when given SNPs (i.e., single nucleotide polymorphisms, or bi-allelic markers that have evolved under the infinite sites assumption). We focus on level-1 phylogenetic networks (i.e., networks where the cycles are node-disjoint), since more complex networks are unidentifiable. We provide a polynomial time quartet-based method that we prove correct for reconstructing the unrooted topology of any level-1 phylogenetic networkN, if we are given a set of SNPs that covers all the bipartitions ofN, even if the ancestral state is not known, provided that the cycles are of length at least 5; we also prove that an algorithm developed by Dan Gusfield in JCSS 2005 correctly recovers the unrooted topology in polynomial time in this case. To the best of our knowledge, this is the first result to establish that the unrooted topology of a level-1 network is uniquely recoverable from SNPs without known ancestral states. We also present a stochastic model for DNA evolution, and we prove that the two methods (our quartet-based method and Gusfield’s method) are statistically consistent estimators of the unrooted topology of the level-1 phylogenetic network. For the case of multi-state homoplasy-free characters, we prove that our quartet-based method correctly constructs the unrooted topology of level-1 networks under the required conditions (all cycles of length at least five), while Gusfield’s algorithm cannot be used in that condition. These results assume that we have access to an oracle for indicating which sites in the DNA alignment are homoplasy-free, and we show that the methods are robust, under some conditions, to oracle errors.
Controlled pH Alteration Enables Guanine Accumulation and Drives Crystallization within Iridosomes
Authors: Eyal Zohar , Gorelick-Ashkenazi Anna , Deis Rachael , Barzilay Yuval , Broder Yonatan , Kellum Asher Perry , Varsano Neta , Hartstein Michal , Sorrentino Andrea , Kaplan-Ashiri Ifat , Rechav Katya , Metzler Rebecca , Houben Lothar , Kronik Leeor , Rez Peter , Gur Dvir 
Published: July 2024

AbstractMany animals exhibit remarkable colors produced by the constructive interference of light reflected from arrays of intracellular guanine crystals. These systems are utilized for various purposes, including vision, camouflage, communication, and thermal regulation. Each guanine crystal forms within a membrane-bound organelle called an iridosome, where precise control over crystal formation occurs. While the presence of guanine crystals in iridosomes is well-documented, the mechanisms facilitating the accumulation of water-insoluble guanine and driving its crystallization remain unclear. Here, we employ advanced imaging and spectroscopy techniques to characterize the maturation of iridosomes in zebrafish iridophores during development. Using cryo-electron microscopy, we found that amorphous guanine accumulates in early-stage iridosomes. Synchrotron-based soft X-ray microscopy studies revealed that, unlike mature crystals, the accumulated guanine is initially in its protonated state. Live imaging with a pH sensor demonstrated that early-stage iridosomes are acidic and that their pH gradually approaches neutrality during maturation. Additionally, the application of a V-ATPase inhibitor reduced the acidity of iridosomes and significantly decreased crystal formation, suggesting the involvement of V-ATPase in regulating the organelle pH. Our findings reveal new insights into the molecular mechanisms facilitating guanine accumulation and crystallization within iridosomes, emphasizing the pivotal role of pH alternations in the precise formation of biogenic crystals.
Lung structural cells are altered by influenza virus leading to rapid immune protection following re-challenge
Authors: Worrell Julie C. , Hargrave Kerrie E. , Finney George E. , Hansell Chris , Cole John , Nijjar Jagtar Singh , Morton Fraser , Pingen Marieke , Purnell Tom , Mitchelson Kathleen , Brennan Euan , Allan Jay , Ilia Georgios , Herder Vanessa , Dietrich Claire Kennedy , Doncheva Yoana , Jamieson Nigel B. , Palmarini Massimo , MacLeod Megan K.L 
Published: July 2024

AbstractLung structural cells, including epithelial cells and fibroblasts, form barriers against pathogens and trigger immune responses following infections such as influenza A virus. This response leads to the recruitment of innate and adaptive immune cells required for viral clearance. Some of these recruited cells remain within the lung following infection and contribute to enhanced viral control following subsequent infections. There is growing evidence that structural cells can also display long-term changes following infection or insults. Here we investigate long-term changes to mouse lung epithelial cells, fibroblasts, and endothelial cells following influenza virus infection and find that all three cell types maintain an imprint of the infection, particularly in genes associated with communication with T cells. Lung epithelial cells from IAV-infected mice display functional changes by more rapidly controlling influenza virus than cells from naïve animals. This rapid anti-viral response and increased expression of molecules required to communicate with T cells demonstrates sustained and enhanced functions following infection. These data suggest lung structural cells could be effective targets for vaccines to boost durable protective immunity.Graphical AbstractHighlightsLung epithelial cells, fibroblasts, and blood endothelial cells maintain an inflammatory imprint of influenza A virus (IAV) infection for at least 40 days post-infection.In vivore-infection leads to a more spatially restricted anti-viral response compared to primary IAV-infected animals.T cells are not required for enhanced viral control early after re-infectionin vivoEx vivolung epithelial cells from IAV-infected mice more rapidly control IAV than cells from naïve animals in the absence of immune cells.
G-quadruplexes are a source of vulnerability inBRCA2deficient granule cell progenitors and medulloblastoma
Authors: Keahi Danielle L. , Sanders Mathijs A. , Paul Matthew R. , Webster Andrew L. H. , Fang Yin , Wiley Tom F. , Shalaby Samer , Carroll Thomas S. , Chandrasekharappa Settara C. , Sandoval-Garcia Carolina , MacMillan Margaret L. , Wagner John E. , Hatten Mary E. , Smogorzewska Agata 
Published: July 2024

AbstractBiallelic pathogenic variants in the essential DNA repair geneBRCA2causes Fanconi anemia, complementation group FA-D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under SHH activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four ofBrca2in the central nervous system, coupled with globalTrp53loss.Brca2Δex3-4;Trp53-/-animals developed SHH subgroup medulloblastomas with complete penetrance. Whole-genome sequencing of the tumors identified structural variants with breakpoints enriched in areas overlapping G-quadruplexes (G4s).Brca2-deficient GCPs exhibited decreased replication speed in the presence of the G4-stabilizer pyridostatin.Pif1helicase, which resolves G4s during replication, was highly upregulated in tumors, andPif1knockout in primary MB tumor cells resulted in increased genome instability upon pyridostatin treatment. These data suggest that G4s may represent sites prone to replication stalling in highly proliferative GCPs and without BRCA2, G4s become a source of genome instability. Tumor cells upregulate G4-resolving helicases to facilitate rapid proliferation through G4s highlighting PIF1 helicase as a potential therapeutic target for treatment ofBRCA2-deficient medulloblastomas.
Evolution of fast-growing piscivorous herring in the young Baltic Sea
Authors: Goodall Jake , Pettersson Mats E. , Bergström Ulf , Cocco Arianna , Delling Bo , Heimbrand Yvette , Karlsson Magnus , Larsson Josefine , Waldetoft Hannes , Wallberg Andreas , Wennerström Lovisa , Andersson Leif 
Published: July 2024

AbstractThe circumstances under which species diversify to genetically distinct lineages is a fundamental question in biology1. Atlantic herring is an extremely abundant zooplanktivorous species that is subdivided into multiple ecotypes that differ regarding spawning time and genetic adaption to local environmental conditions such as temperature, salinity, and light conditions2,3. Here we show using whole genome analysis that multiple populations of piscivorous (fish-eating) herring have evolved sympatrically after the colonization of the brackish Baltic Sea within the last 8,000 years postglaciation. The piscivorous ecotype grows faster, and is much larger and less abundant than the zooplanktivorous Baltic herring. Lesions of the gill rakers in the piscivorous ecotype indicated incomplete adaptation to a fish diet. This niche expansion of herring in the young Baltic Sea with its paucity of piscivorous species suggests that empty niche space is more important than geographic isolation for the evolution of biodiversity.
Centennial recovery of recent human-disturbed forests
Authors: Rodríguez-Uña Asun , Cruz-Alonso Verónica , López-López José A. , Moreno-Mateos David 
Published: July 2024

AbstractInternational commitments are challenging countries to restore their degraded lands, particularly forests. These commitments require global assessments of recovery timescales and trajectories of different forest attributes to inform restoration strategies. We use a meta-chronosequence approach including 125 forest chronosequences to reconstruct past (c. 300 years), and model future recovery trajectories of forests recovering from agriculture and logging impacts. We found recovering forests significantly differed from undisturbed ones after 150 years and projected that difference to remain for up to 218 (38-745) or 494 (92-2,039) years for ecosystem attributes like nitrogen stocks or species similarity, respectively. These conservative estimates, however, do not capture the complexity of forest ecosystems. A centennial recovery of forests requires strategic, unprecedented planning to deliver a restored world.
SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma
Authors: Miao Bisi , Ge Ling , He Chenxi , Wang Xinghao , Wu Jibo , Li Xiang , Chen Kun , Wan Jinkai , Xing Shenghui , Ren Lingnan , Shi Zhennan , Flores Natasha M. , Liang Zhihui , Xu Xinyi , Wang Ruoxin , Cheng Jingdong , Mao Yuanhui , Mazur Pawel K. , Cai Jiabin , Lan Fei 
Published: July 2024

AbstractWhile lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center (GAC), was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robustin vitroactivity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma (HCC) and negatively correlated with patient prognosis. Depleting SMYD5 renders HCC cells hypersensitivity to mTOR inhibition in both 2D and 3D cultures. Additionally, the loss of SMYD5 markedly inhibits HCC development and growth in both genetically engineered mouse (GEM) and patient-derived xenograft (PDX) models, with the inhibitory effect in the PDX model further enhanced by concurrent mTOR suppression. Our findings reveal a novel role of the SMYD5 and RPL40 K22me3 axis in translation elongation and highlight the therapeutic potential of targeting SMYD5 in HCC, particularly with concurrent mTOR inhibition. This work also broadens the understanding of lysine methylation, extending its significance from transcriptional regulation to translational control.
Dengue virus structural proteins are expressed on the surface of DENV-infected cells and are a target for antibody-dependent cellular phagocytosis
Authors: Waldran Mitchell J. , Kurtz Elizabeth A. , Gebo Chad J. , Rooney Timothy J. , Middleton Frank A. , Roy Nathan H. , Currier Jeffrey R. , Waickman Adam T. 
Published: July 2024

ABSTRACTDengue virus (DENV) is an arboviral pathogen found in over 100 countries and a source of significant morbidity and mortality. While the mechanisms underpinning the pathophysiology of severe dengue are incompletely understood, it has been previously suggested that antibodies directed against the DENV envelope (E) protein can facilitate antibody dependent enhancement (ADE) of the infection, increasing the number of infected cells and the severity of infection in an exposed individual. Accordingly, there is interest in defining mechanisms for directly targeting DENV-infected cells for immunologic clearance, an approach that bypasses the risk of ADE. We have previously demonstrated that antibodies specific for DENV non-structural protein 1 (NS1) can opsonize and facilitate the phagocytic clearance of DENV infected cells. However, it is currently unclear if other DENV antigens are expressed on the surface of infected cells, and if these antigens can be targeted by antibody-dependent clearance mechanisms. In this study, we demonstrate that DENV structural proteins are expressed on the surface of DENV-infected cells, and that these antigens can be opsonized by both DENV-immune sera and monoclonal antibodies. In addition, DENV E-specific antibodies can facilitate phagocytic uptake of DENV-infected cells, resulting in the target-cell membrane localizing to endosomes of the engulfing phagocyte. Notably, no DENV genetic material was observed localizing to the engulfing phagocyte, suggesting that horizontal transfer of DENV from the infecting cell is an unlikely occurrence. In their totality, these data reinforce the concept that DENV E-reactive antibodies have a multifaceted role in DENV immunity and pathogenesis beyond neutralization and/or infection-enhancement.
Continuous Monitoring of Glucose and Oxygen using an Insertable Biomaterial-based Multianalyte Barcode Sensor
Authors: Pradhan Ridhi , Chimene David , Ko Brian S. , Goncharov Artem , Ozcan Aydogan , McShane Michael J. 
Published: July 2024

ABSTRACTChronic diseases including diabetes, cardiovascular diseases, and microvascular complications contribute significantly to global morbidity and mortality. Multiplexing technologies offer a promising approach for the simultaneous detection and management of comorbidities, providing comprehensive disease insights. In this work, we describe a miniaturized optical “barcode” sensor with high biocompatibility for continuous monitoring of glucose and oxygen. This enzymatic sensor relies on oxygen consumption in proportion to local glucose levels and the phosphorescence reporting of tissue oxygen with a lifetime-based probe. The sensor was designed to operate in a tissue environment with low levels of dissolved oxygen. The barcode sensor consists of a poly(ethylene) glycol diacrylate (PEGDA) hydrogel with four discrete compartments separately filled with glucose or oxygen-sensing phosphorescent microparticles. We evaluated the response of the barcode hydrogels to fluctuating glucose levels over the physiological range under low oxygen conditions, demonstrating controlled tuning of dynamic range and sensitivity. Moreover, the barcode sensor exhibited remarkable storage stability over 12 weeks, along with full reversibility and excellent reproducibility (∼6% variability in phosphorescence lifetime). Electron beam sterilization had a negligible impact on the glucose response of the barcode sensors. Furthermore, our investigation revealed minimal phosphorescence lifetime changes in oxygen compartments while exhibiting increased lifetime in glucose-responsive compartments when subjected to alternating glucose concentrations (0 and 200 mg/dL), showcasing the sensor’s multianalyte sensing capabilities without crosstalk between compartments. Additionally, evaluation of tissue response to sensors inserted in pigs revealed appropriate biocompatibility of the barcodes.
Metabolomics profiling reveals association of fermented herbal feed additive, growth performance and gut microbiota in piglets
Authors: Xiao Ruiming , Wang Lingling , Tang Zhiqiang , Qian Xueqiao , Wang Jian , Lian Yingli , Tang Jiayi , Xu Jiarou , Lin Ying , Shi Baojun , Xu Pan , Xiong Qiongsi 
Published: July 2024

AbstractFermented Chinese medicine (FCM), as a functional feed additive, has been widely recognized to play a significant role in protecting the intestinal health of piglets and enhancing productive performance. However, the relationship between the active components of FCM, gut microbiota, and their beneficial effects on animal performance remains unclear. In this study, metabolomics analysis revealed a significant increase in the main contents of lactic acid and propionic acid in FCM, while most glycosides and their derivatives decreased after three days of microbial fermentation. Subsequently, piglets were fed a basic diet supplemented with 1% FCM, while the control group received only the basic diet. The results indicated a significant increase in feed intake and average daily gain within 14 days (P<0.05) due to FCM supplementation. Additionally, FCM significantly improved feed efficiency from 1.76 to 1.50 (P<0.05). Meanwhile, piglets in the FCM group exhibited significantly lower frequencies of diarrhea and coughing, indicating better health. Moreover, high-throughput sequencing analysis revealed higher abundances ofLactobacillus agilis,Megasphaera elsdenii,Ligilactobacillus, andVeillonellaceaein piglets fed with FCM. In summary, FCM increased the content of active ingredients through microbial fermentation and regulated the intestinal microbiota to improve the health of piglets. FCM offers a promising potential for enhancing production performance and economic efficiency in the livestock industry.
Pollen Trapping As Honeybees Pollination Management and Identification of Dominant Pollinators of Guizotia abyssinica (L.f)
Authors: Jilo Kasim Roba , Yadeta Gemmechis Legesse , Gemmeda Tolera Kumsa 
Published: July 2024

AbstractPollination is one of the most fascinating aspects of insect-plant interactions. Pollen is the male reproductive element of flowering plants, gathered by foraging Honeybees from the male parts of flowering plants called the anther. Guizotia abyssinica (L.f) is an important oilseed crop cultivated in Ethiopia and India, which belongs to the family Asteraceae. Although self-incompatibility is found in Guizotia abyssinica, a higher seed set is experienced in places with an active Honeybees population. Agricultural practices usually focus on inputs such as fertilizer application to improve seed yield of Guizotia abyssinica. However, these practices have little effect on yield if the availability of insect pollination is too low. To fill this gap, an experiment was carried out at Dandi district, West Shao zone, Oromia, Ethiopia to see the effect of Honeybees pollination management as an agronomic input. Pollination management of Honeybees was tested under feeding and non-feeding of colonies management. Pollen was trapped with and without sugar syrup feeding. The results discovered that Honeybees fed sugar syrup collected much more pollen than colonies not fed sugar syrup. The proportion of Guizotia abyssinica pollen collected through sugar syrup feeding of the colony was greater (62.2%), compared to the proportion of Guizotia abyssinica pollen trapped without sugar syrup feeding (37.8%). This indicates that sugar syrup feeding enhances the collection of pollen and probably enhances the pollination efficiency of Honeybees since they visit frequently to fulfill their daily protein requirement of pollen. Therefore, Honeybees pollination services should be included as one of the agronomic inputs with sugar syrup feeding as pollination management that might increase the yield of Guizotia abyssinica since it increases visiting frequency.
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC
Authors: Abdelazeem Khalid N.M. , Nguyen Diemmy , Corbo Sophia , Darragh Laurel B. , Matsumoto Mike W. , Van Court Benjamin , Neupert Brooke , Yu Justin , Olimpo Nicholas A. , Osborne Douglas Grant , Gadwa Jacob , Ross Richard B. , Nguyen Alexander , Bhatia Shilpa , Kapoor Mohit , Friedman Rachel S. , Jacobelli Jordan , Saviola Anthony J. , Knitz Michael W. , Pasquale Elena B. , Karam Sana D. 
Published: July 2024

AbstractThe EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) poses a significant challenge to rational drug design. We find that EphB4 knockdown in cancer cells enhances metastasis in preclinical HNSCC models by augmenting immunosuppressive cells like T regulatory cells (Tregs) within the tumor microenvironment. EphB4 inhibition in cancer cells also amplifies their ability to metastasize through increased expression of genes associated with epithelial mesenchymal transition and hallmark pathways of metastasis. In contrast, vascular ephrinB2 knockout coupled with radiation therapy (RT) enhances anti-tumor immunity, reduces Treg accumulation into the tumor, and decreases metastasis. Notably, targeting the EphB4-ephrinB2 signaling axis with the engineered EphB4 ligands EFNB2-Fc-His and Fc-TNYL-RAW-GS reduces local tumor growth and distant metastasis in a preclinical model of HNSCC. Our data suggest that targeted inhibition of vascular ephrinB2 while avoiding inhibition of EphB4 in cancer cells could be a promising strategy to mitigate HNSCC metastasis.