bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of genetic diversity and population structure using glutenin protein markers in various wheat varieties
Authors: Rai Anjali , Singh Santosh K. , Singh Sumit K. , Sharma Poornima , Ahlawat Arvind K. , Han Sung Soo , Mahendru-Singh Anju 
Published: June 2023

AbstractThe study of polymorphism of glutenin makes it possible to identify and isolate desirable genotypes with higher grain quality. In the last few years, only a part of the genetic diversity among the modern and popular wheat germplasm and varieties based on the polymorphism of glutenin subunits are captured. To address this 107 wheat varieties released across different agricultural zones in India, were used to investigate HMW-GS and LMW-GS allele polymorphism, gene diversity and genetic variation in the Glu-1 and Glu-3 loci. Among the different HMW-GS, the highest genetic variation was observed at the Glu-D1 locus with both Glu-D1a and Glu-D1d possessing genetic variation of 0.490, 0.484 respectively. The highest genetic variation at the Glu-A3 locus was observed at the Glu-A3c and GluA3b possessing a genetic variation of 0.463, 0.411 respectively. This was followed by the Glu-B3j having a genetic variation of 0.386 at the Glu-B3 locus. Over 20 years a remarkable increase in the Glu-D1d allele is observed in the newly released varieties in India. Among all the zones, Glu-A1-null is the least frequent allele at the Glu-1 locus, however, it is present as the predominant allele in the NHZ of India. This study elucidates the relationships of these HMW and LMW allelic frequencies and genetic variation with their geographical distribution over the two different periods. This study provides reference data that can be used to assist the breeding, quality evaluation and development of good-quality wheat varieties.
Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective
Authors: Fratta Elisabetta , Giurato Giorgio , Guerrieri Roberto , Colizzi Francesca , Dal Col Jessica , Weisz Alessandro , Steffan Agostino , Montico Barbara 
Published: June 2023

AbstractMacroautophagy, hereafter referred to as autophagy, represents a highly conserved catabolic process that maintains cellular homeostasis. At present, the role of autophagy in cutaneous melanoma (CM) is still controversial, since it appears to be tumor-suppressive at early stages of malignant transformation and cancer-promoting during disease progression. Interestingly, autophagy has been found to be often increased in CM harboring BRAF mutation and to impair the response to targeted therapy. In addition to autophagy, numerous studies have recently conducted in cancer to elucidate the molecular mechanisms of mitophagy, a selective form of mitochondria autophagy, and secretory autophagy, a process that facilitates unconventional cellular secretion. Although several aspects of mitophagy and secretory autophagy have been investigated in depth, their involvement in BRAF-mutant CM biology has only recently emerged. In this review, we aim to overview autophagy dysregulation in BRAF-mutant CM, along with the therapeutic advantages that may arise from combining autophagy inhibitors with targeted therapy. In addition, the recent advances on mitophagy and secretory autophagy involvement in BRAF-mutant CM will be also discussed. Finally, since a number of autophagy-related non-coding RNAs (ncRNAs) have been identified so far, we will briefly discussed recent advances linking ncRNAs to autophagy regulation in BRAF-mutant CM.
Aurora kinase A/AURKA functionally interacts with the mitochondrial ATP synthase to regulate energy metabolism and cell death
Authors: Sharma Rakesh Kumar , Chafik Abderrahman , Bertolin Giulia 
Published: June 2023

AbstractCancer cells often hijack metabolic pathways to obtain the energy required to sustain their proliferation. Understanding the molecular mechanisms underlying cancer cell metabolism is key to fine-tune the metabolic preference of specific tumors, and potentially offer new therapeutic strategies. Here, we show that the pharmacological inhibition of mitochondrial Complex V delays the cell cycle by arresting breast cancer cell models in the G0/G1 phase. Under these conditions, the abundance of the multifunctional protein Aurora kinase A/AURKA is specifically lowered. We then demonstrate that AURKA functionally interacts with the mitochondrial Complex V core subunits ATP5F1A and ATP5F1B. Altering the AURKA/ATP5F1A/ATP5F1B nexus is sufficient to trigger G0/G1 arrest, and this is accompanied by decreased glycolysis and mitochondrial respiration rates. Last, we discover that the roles of the AURKA/ATP5F1A/ATP5F1B nexus depend on the specific metabolic propensity of triple-negative breast cancer cell lines, where they correlate with cell fate. On one hand, the nexus induces G0/G1 arrest in cells relying on oxidative phosphorylation as the main source of energy. On the other hand, it allows to bypass cell cycle arrest and it triggers cell death in cells with a glycolytic metabolism. Altogether, we provide evidence that AURKA and mitochondrial Complex V subunits cooperate to maintain cell metabolism in breast cancer cells. Our work paves the way to novel anti-cancer therapies targeting the AURKA/ATP5F1A/ATP5F1B nexus to lower cancer cell metabolism and proliferation.
Targeting lysine-specific demethylase 1 (KDM1A/LSD1) impairs colorectal cancer tumorigenesis by affecting cancer cells stemness, motility, and differentiation
Authors: Antona Annamaria , Leo Giovanni , Favero Francesco , Varalda Marco , Venetucci Jacopo , Faletti Stefania , Todaro Matilde , Mazzucco Eleonora , Soligo Enrica , Saglietti Chiara , Stassi Giorgio , Manfredi Marcello , Pelicci Giuliana , Corà Davide , Valente Guido , Capello Daniela 
Published: June 2023

AbstractAmong all cancers, colorectal cancer (CRC) is the 3rd most common and the 2nd leading cause of death worldwide. New therapeutic strategies are required to target cancer stem cells (CSCs), a subset of tumor cells highly resistant to present-day therapy and responsible for tumor relapse. CSCs display dynamic genetic and epigenetic alterations that allow quick adaptations to perturbations. Lysine-specific histone demethylase 1A (KDM1A also known as LSD1), a FAD-dependent H3K4me1/2 and H3K9me1/2 demethylase, was found to be upregulated in several tumors and associated with a poor prognosis due to its ability to maintain CSCs staminal features. Here, we explored the potential role of KDM1A targeting in CRC by characterizing the effect of KDM1A silencing in differentiated and CRC stem cells (CRC-SCs). In CRC samples, KDM1A overexpression was associated with a worse prognosis, confirming its role as an independent negative prognostic factor of CRC. Consistently, biological assays such as methylcellulose colony formation, invasion, and migration assays demonstrated a significantly decreased self-renewal potential, as well as migration and invasion potential upon KDM1A silencing. Our untargeted multi-omics approach (transcriptomic and proteomic) revealed the association of KDM1A silencing with CRC-SCs cytoskeletal and metabolism remodeling towards a differentiated phenotype, supporting the role of KDM1A in CRC cells stemness maintenance. Also, KDM1A silencing resulted in up-regulation of miR-506-3p, previously reported to play a tumor-suppressive role in CRC. Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A impacts CRC progression in several non-overlapping ways, and therefore it represents a promising epigenetic target to prevent tumor relapse.
Neutrophil diversity and plasticity: Implications for organ transplantation
Authors: Qu Junwen , Jin Jingsi , Zhang Ming , Ng Lai Guan 
Published: June 2023

AbstractNeutrophils, as the first defenders against external microbes and stimuli, are highly active and finely regulated innate immune cells. Emerging evidence has challenged the conventional dogma that neutrophils are a homogeneous population with a short lifespan that promotes tissue damage. Recent findings on neutrophil diversity and plasticity in homeostatic and disease states have centered on neutrophils in the circulation. In contrast, a comprehensive understanding of tissue-specialized neutrophils in health and disease is still lacking. This article will first discuss how multiomics advances have contributed to our understanding of neutrophil heterogeneity and diversification in resting and pathological settings. This discussion will be followed by a focus on the heterogeneity and role of neutrophils in solid organ transplantation and how neutrophils may contribute to transplant-related complications. The goal of this article is to provide an overview of the research on the involvement of neutrophils in transplantation, with the aim that this may draw attention to an underappreciated area of neutrophil research.
Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice
Authors: Whitehead Michael , Sage Andrew , Burgoyne Tom , Osborne Andrew , Yu-Wai-Man Patrick , Martin Keith R. 
Published: June 2023

AbstractAdeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be phosphorylated/ubiquitinated in the cytosol, facilitating degradation of the vector and the inhibition of transduction. As such, mutation of phosphodegron residues have been correlated with increased transduction of target cells, however, an assessment of the immunobiology of wild-type and phosphodegron mutant AAV2 vectors following intravitreal (IVT) delivery to immunocompetent animals is lacking in the current literature. In this study, we show that IVT of a triple phosphodegron mutant AAV2 capsid is associated with higher levels of humoral immune activation, infiltration of CD4 and CD8 T-cells into the retina, generation of splenic germinal centre reactions, activation of conventional dendritic cell subsets, and elevated retinal gliosis compared to wild-type AAV2 capsids. However, we did not detect significant changes in electroretinography arising after vector administration. We also demonstrate that the triple AAV2 mutant capsid is less susceptible to neutralisation by soluble heparan sulphate and anti-AAV2 neutralising antibodies, highlighting a possible utility for the vector in terms of circumventing pre-existing humoral immunity. In summary, the present study highlights novel aspects of rationally-designed vector immunobiology, which may be relevant to their application in preclinical and clinical settings.
Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid
Authors: Wei Wenchao , Wong Chi Chun , Jia Zhongjun , Liu Weixin , Liu Changan , Ji Fenfen , Pan Yasi , Wang Feixue , Wang Guoping , Zhao Liuyang , Chu Eagle S. H. , Zhang Xiang , Sung Joseph J. Y. , Yu Jun 
Published: June 2023

AbstractNon-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of 13C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by 13C-inulin. Integration of 13C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease.
An anti-biofilm cyclic peptide targets a secreted aminopeptidase from P. aeruginosa
Authors: Harding Christopher John , Bischoff Marcus , Bergkessel Megan , Czekster Clarissa Melo 
Published: June 2023

AbstractPseudomonas aeruginosa is an opportunistic pathogen that causes serious illness, especially in immunocompromised individuals. P. aeruginosa forms biofilms that contribute to growth and persistence in a wide range of environments. Here we investigated the aminopeptidase, P. aeruginosa aminopeptidase (PaAP) from P. aeruginosa, which is highly abundant in the biofilm matrix. PaAP is associated with biofilm development and contributes to nutrient recycling. We confirmed that post-translational processing was required for activation and PaAP is a promiscuous aminopeptidase acting on unstructured regions of peptides and proteins. Crystal structures of wild-type enzymes and variants revealed the mechanism of autoinhibition, whereby the C-terminal propeptide locks the protease-associated domain and the catalytic peptidase domain into a self-inhibited conformation. Inspired by this, we designed a highly potent small cyclic-peptide inhibitor that recapitulates the deleterious phenotype observed with a PaAP deletion variant in biofilm assays and present a path toward targeting secreted proteins in a biofilm context.
Readout of histone methylation by Trim24 locally restricts chromatin opening by p53
Authors: Isbel Luke , Iskar Murat , Durdu Sevi , Weiss Joscha , Grand Ralph S. , Hietter-Pfeiffer Eric , Kozicka Zuzanna , Michael Alicia K. , Burger Lukas , Thomä Nicolas H. , Schübeler Dirk 
Published: June 2023

AbstractThe genomic binding sites of the transcription factor (TF) and tumor suppressor p53 are unusually diverse with regard to their chromatin features, including histone modifications, raising the possibility that the local chromatin environment can contextualize p53 regulation. Here, we show that epigenetic characteristics of closed chromatin, such as DNA methylation, do not influence the binding of p53 across the genome. Instead, the ability of p53 to open chromatin and activate its target genes is locally restricted by its cofactor Trim24. Trim24 binds to both p53 and unmethylated histone 3 lysine 4 (H3K4), thereby preferentially localizing to those p53 sites that reside in closed chromatin, whereas it is deterred from accessible chromatin by H3K4 methylation. The presence of Trim24 increases cell viability upon stress and enables p53 to affect gene expression as a function of the local chromatin state. These findings link H3K4 methylation to p53 function and illustrate how specificity in chromatin can be achieved, not by TF-intrinsic sensitivity to histone modifications, but by employing chromatin-sensitive cofactors that locally modulate TF function.
Touch events and human activities for continuous authentication via smartphone
Authors: Gattulli Vincenzo , Impedovo Donato , Pirlo Giuseppe , Volpe Francesco 
Published: June 2023

AbstractThe security of modern smartphones is related to the combination of Continuous Authentication approaches, Touch events, and Human Activities. The approaches of Continuous Authentication, Touch Events, and Human Activities are silent to the user but are a great source of data for Machine Learning Algorithms. This work aims to develop a method for continuous authentication while the user is sitting and scrolling documents on the smartphone. Touch Events and Smartphone Sensor Features (from the well-known H-MOG Dataset) were used with the addition, for each sensor, of the feature called Signal Vector Magnitude. Several Machine Learning Models have been considered with different experiment setups, 1-class, and 2-class, for evaluation. The results show that the 1-class SVM achieves an accuracy of 98.9% and an F1-score of 99.4%, considering the selected features and the feature Signal Vector Magnitude very significant.
A composite fishing index to support the monitoring and sustainable management of world fisheries
Authors: Ye Yimin , Link Jason S. 
Published: June 2023

AbstractOverfishing has severe social, economic, and environmental ramifications. Eliminating global overfishing is one of the United Nations’ Sustainable Development Goals (SDGs). The SDGs require effective policy and progress monitoring. However, current indicators are issue-specific and cannot be utilized to measure fisheries efficacy holistically. This study develops a comprehensive index that takes into account the inputs, outputs, and ecological implications of fisheries. These components are then merged to form a single composite fishing index that evaluates both total fishing pressure on the ecosystem and historical patterns. The global fishing intensity grew by a factor of eleven between 1950 and 2017, and geographical differences emerged. The fishing intensity of developed countries peaked in 1997 and has since fallen due to management, but developing countries’ fishing intensity has increased continuously over the whole research period, with quasi-linear growth after 1980. Africa has experienced the most rapid expansion in fishing activity and now has the highest fishing intensity. This index takes a more comprehensive and objective look at fisheries. Its worldwide spatial–temporal comparison enables the identification of similar temporal trends across countries or regions, as well as areas of uneven development and hotspot sites for targeted policy action.
Impact of sea level rise on the Mediterranean Lithophyllum byssoides rims
Authors: Blanfuné Aurélie , Boudouresque Charles-François , Verlaque Marc , Minne Antoine , Noisette Fanny , Thibaut Thierry 
Published: June 2023

AbstractThe calcified red macroalga Lithophyllum byssoides, a very common midlittoral species in the western Mediterranean Sea, is a significant ecosystem engineer capable, under exposed and dim light conditions, of building wide and solid endemic bioconstructions near the mean sea level: the L. byssoides rims or 'trottoirs à L. byssoides'. Although the growth of the species is relatively rapid for a calcified alga, the construction of a large rim requires several centuries of near stable or slowly rising sea level. As the time scale of their formation is measured in centuries, L. byssoides bioconstructions constitute valuable and sensitive sea level markers. The health status of L. byssoides rims has been studied at two sites located far apart from each other (Marseille and Corsica), both in areas heavily impacted by humans and in areas with little impact (MPAs and unprotected areas). A health index is proposed: Lithophylum byssoides Rims Health Index. The main and inevitable threat is the rise in the sea level. This ecosystem would be the first case worldwide of marine ecosystem collapse resulting, indirectly, from man-induced global change.
Establishment of a protocol to administer immunosuppressive drugs for iPS cell-derived cardiomyocyte patch transplantation in a rat myocardial infarction model
Authors: Ito Emiko , Kawamura Ai , Kawamura Takuji , Takeda Maki , Harada Akima , Mochizuki-Oda Noriko , Sawa Yoshiki , Miyagawa Shigeru 
Published: June 2023

AbstractTransplantation of human allogeneic induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a new, promising treatment for severe heart failure. However, immunorejection is a significant concern in allogeneic hiPSC-CM transplantation, requiring the administration of several immunosuppressive agents. An appropriate protocol for the administration of immunosuppressants may substantially affect the efficacy of hiPSC-CM transplantation in case of heart failure owing to allogeneic transplantation. In this study, we investigated the effect of immunosuppressant administration duration on the efficacy and safety of allogenic hiPSC-CM patch transplantation. We used a rat model of myocardial infarction to evaluate cardiac function using echocardiography six months after the transplantation of hiPSC-CM patches with immunosuppressant administration for either two or four months and compared them to control rats (sham operation, no immunosuppressant administration). Histological analysis performed at 6 months after hiPSC-CM patch transplantation revealed significant improvement in cardiac function in immunosuppressant-treated rats compared with those in the control group. Moreover, fibrosis and cardiomyocyte size was significantly reduced and the number of structurally mature blood vessels was significantly increased in the immunosuppressant-treated rats compared to control rats. However, there were no significant differences between the two immunosuppressant-treated groups. Our results show that prolonged administration of immunosuppressive agents did not enhance the effectiveness of hiPSC-CM patch transplantation, and therefore, highlight the importance of an appropriate immunological regimen for the clinical application of such transplantation.
Combination of expert guidelines-based and machine learning-based approaches leads to superior accuracy of automated prediction of clinical effect of copy number variations
Authors: Sládeček Tomáš , Gažiová Michaela , Kucharík Marcel , Zaťková Andrea , Pös Zuzana , Pös Ondrej , Krampl Werner , Tomková Erika , Hýblová Michaela , Minárik Gabriel , Radvánszky Ján , Budiš Jaroslav , Szemes Tomáš 
Published: June 2023

AbstractClinical interpretation of copy number variants (CNVs) is a complex process that requires skilled clinical professionals. General recommendations have been recently released to guide the CNV interpretation based on predefined criteria to uniform the decision process. Several semiautomatic computational methods have been proposed to recommend appropriate choices, relieving clinicians of tedious searching in vast genomic databases. We have developed and evaluated such a tool called MarCNV and tested it on CNV records collected from the ClinVar database. Alternatively, the emerging machine learning-based tools, such as the recently published ISV (Interpretation of Structural Variants), showed promising ways of even fully automated predictions using broader characterization of affected genomic elements. Such tools utilize features additional to ACMG criteria, thus providing supporting evidence and the potential to improve CNV classification. Since both approaches contribute to evaluation of CNVs clinical impact, we propose a combined solution in the form of a decision support tool based on automated ACMG guidelines (MarCNV) supplemented by a machine learning-based pathogenicity prediction (ISV) for the classification of CNVs. We provide evidence that such a combined approach is able to reduce the number of uncertain classifications and reveal potentially incorrect classifications using automated guidelines. CNV interpretation using MarCNV, ISV, and combined approach is available for non-commercial use at https://predict.genovisio.com/.