bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice Humanized for Major Histocompatibility Complex and Angiotensin-Converting Enzyme 2 with High Permissiveness to SARS-CoV-2 Omicron Replication
Authors: Chevalier Fabien Le , Authié Pierre , Chardenoux Sébastien , Bourgine Maryline , Vesin Benjamin , Cussigh Delphine , Sassier Yohann , Fert Ingrid , Noirat Amandine , Nemirov Kirill , Anna François , Bérard Marion , Guinet Françoise , Hardy David , Charneau Pierre , Lemonnier François , Langa-Vives Francina , Majlessi Laleh 
Published: December 2022

AbstractHuman Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike glycoprotein. The murine ACE2 ortholog does not interact efficiently with SARS-CoV-2 Spike and therefore the conventional laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated newhACE2transgenic mice, which harbor thehACE2gene under the human keratin 18 promoter, in C57BL/6 “HHD-DR1” background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with varioushACE2mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. Compared to the previously available B6.K18-ACE22Prlmn/JAXmice, which have limited permissiveness to SARS-CoV-2 Omicron replication, these three new hACE2 transgenic strains display higher levels ofhACE2mRNA expression, associated with high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral vector-based COVID-19 vaccine candidate.
Multiomic Profiling of Human Clonal Hematopoiesis Reveals Genotype and Cell-Specific Inflammatory Pathway Activation
Authors: Heimlich J. Brett , Bhat Pawan , Parker Alyssa C. , Jenkins Matthew T. , Vlasschaert Caitlyn , Ulloa Jessica , Van Amburg Joseph C. , Potts Chad R. , Olson Sydney , Silver Alexander J. , Ahmad Ayesha , Sharber Brian , Brown Donovan , Hu Ningning , van Galen Peter , Savona Michael R. , Bick Alexander G. , Ferrell P. Brent 
Published: December 2022

AbstractClonal hematopoiesis (CH) is an age-associated phenomenon that increases risk for hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood1. Here, we profile peripheral blood gene expression in 66,968 single cells from a cohort of 17 CH patients and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutantTET2andDNMT3Acells to non-mutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment. Additionally, patients harboringDNMT3AandTET2CH mutations possessed a pro-inflammatory profile in CD14+ monocytes through previously unrecognized pathways such as galectin and macrophage Inhibitory Factor (MIF). We also found that T cells from CH patients, though mostly un-mutated, had decreased expression of GTPase of the immunity associated protein (GIMAP) genes, which are critical to T cell development, suggesting that CH may impair T cell function.Key points- CD14+ monocytes from clonal hematopoiesis patients stimulate inflammation through increased cytokine expression.- T cells from clonal hematopoiesis are deficient in GIMAP expression, suggesting CH may impair T cell differentiation.
The Impact of Peri-implantitis on the Proteome Biology of Crevicular Fluid: A pilot study
Authors: Halstenbach Tim , Nelson Katja , Iglhaut Gerhard , Schilling Oliver , Fretwurst Tobias 
Published: December 2022

AbstractBackgroundThe proteome of the peri-implant crevicular fluid (PICF) has not been systematically investigated. The aim of the present study was to reveal the proteome biology of dental implants affected with peri-implantitis.MethodsPatients with at least one diseased implant were included (probing depth ≥ 6 mm, ≥ 3 mm peri-implant radiological bone loss). Using sterile paper strips, samples were collected from healthy implants (I), healthy teeth (T) and peri-implantitis affected implants (P). Proteome analysis was performed using liquid chromatography – tandem mass spectrometry (LC-MS/MS) and data independent acquisition, allowing the identification and quantification of human and bacterial proteins as well as semi-specific peptides.Results38 samples from 13 patients were included in the study. 2332 different human proteins were identified across all samples. No differentially expressed proteins between T and I were found. Comparing P to I, 59 proteins were found upregulated and 31 downregulated in P with significance. Upregulated proteins included proinflammatory proteins such as immunoglobulins, dysferlin and S100P, as well as antimicrobial proteins, e.g. myeloperoxidase or azurocidin. Gene ontology analysis further revealed higher activity of immunological pathways. Proteolytic patterns indicated the activity of inflammatory proteins such as cathepsin G. 334 bacterial proteins were identified and quantified. Peri-implantitis showed elevated proteolytic activity.ConclusionI and T share similarities in their proteome, while diseased implants deviate strongly from healthy conditions. The PICF proteome of peri-implantitis affected sites exhibits an inflammatory fingerprint, dominated by neutrophile activity when compared to healthy implants.SummaryProteomic analysis of the peri-implant crevicular fluid revealed distinct proteome alterations in peri-implantitis when compared to healthy implants and teeth, while healthy teeth and implants share strong similarities.
Investigation on key aspects of mating biology in the mosquitoAedes koreicus
Authors: Ciocchetta Silvia , Frentiu Francesca D , Montarsi Fabrizio , Capelli Gioia , Devine Gregor J 
Published: December 2022

AbstractAedes koreicusis a mosquito (Diptera: Culicidae) from Northeast Asia with a rapidly expanding presence outside its original native range. Over the years the species has been discovered in several new countries, either spreading after first introduction or remaining localised to limited areas. Notably, recent studies have demonstrated the ability of the species to transmit zoonotic parasites and viruses both in the field and in laboratory settings. Combined with its invasive potential, the possible role ofAe. koreicusin pathogen transmission highlights the public health risks of its invasion. In this study, we used a recently established population from Italy to investigate aspects of biology that influence reproductive success inAe. koreicus: autogeny, mating behaviour, mating disruption by the sympatric invasive speciesAedes albopictus, and the presence of the endosymbiontWolbachia pipientis.Our laboratory population did not exhibit autogenic behaviour and required a blood meal to complete its ovarian cycle. When we exposedAe. koreicusfemales to males ofAe. albopictus, we observed repeated attempts at insemination and an aggressive, disruptive mating behaviour initiated by males. Despite this, no sperm was identified inAe. koreicusspermathecae. Wolbachiawas not detected in thisAe. koreicuspopulation and therefore had no effect onAe. koreicusreproduction.
CD244 regulates both innate and adaptive immune axes in melanoma by inhibiting autophagy-mediated M1 macrophage maturation
Authors: Kim Jeongsoo , Kim Tae-Jin , Chae Sehyun , Park Sunghee , Ha Hyojeong , Park Yejin , Yoon Chul Joo , Kim Jiyoung , Kim Jungwon , Im Kyungtaek , Lee Hyemin , Lee Kyunghye , Kim Jeongmin , Kim Daham , Lee Eunju , Shin Min Hwa , Park Serk In , Rhee Inmoo , Lee Jeewon , Lee Keun Hwa , Hwang Daehee , Lee Kyung-Mi 
Published: December 2022

AbstractAccumulating data have highlighted the role of monocytes/macrophages in immune escape by generating immunologically “cold” tumors that do not respond to immunotherapy. CD244 (SLAMF4, 2B4), a member of the signaling lymphocyte activation molecule family, is expressed on myeloid cells, but its precise role has not been elucidated. Using monocyte lineage-specific CD244-deficient (LysM-cre+/-CD244fl/fl;cKO) mice challenged with B16F10 melanoma, we report for the first time that CD244 negatively regulates tumor immunity by inhibiting the differentiation and functional maturation of CD11b+Ly6ChiF4/80lomonocytes into CD11b+Ly6CloF4/80himacrophages within the tumor microenvironment. CD244-deficient macrophages more effectively activated antigen-specific T cell responses compared to WT macrophages, thus delaying tumor growth in the B16F10 melanoma model. Moreover, combinatorial intervention of anti-PD-L1 antibodies with CD244-KO BMDM markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with WT BMDM. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset (SCP398 from single-cell portal), revealed 221 differentially expressed genes of CD244-monocytes/macrophages were associated with phagocytosis, antigen presentation, and autophagy. Additionally, cell type deconvolution analysis within melanoma patients bulk RNA-seq datasets from TCGA database, revealed presence of CD244- monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. Hence, we proposed that CD244 serve as a critical immune checkpoint receptor on macrophages, and CD244-deficient macrophages may represent a novel therapeutic modality to convert immunologically “cold” tumors to “hot” tumors, which can function synergistically with checkpoint blockade therapies.
Variational inference accelerates accurate DNA mixture deconvolution
Authors: Susik Mateusz , Sbalzarini Ivo F. 
Published: December 2022

AbstractWe investigate a class of DNA mixture deconvolution algorithms based on variational inference, and we show that this can significantly reduce computational runtimes with little or no effect on the accuracy and precision of the result. In particular, we consider Stein Variational Gradient Descent (SVGD) and Variational Inference (VI) with an evidence lower-bound objective. Both provide alternatives to the commonly used Markov-Chain Monte-Carlo methods for estimating the model posterior in Bayesian probabilistic genotyping. We demonstrate that both SVGD and VI significantly reduce computational costs over the current state of the art. Importantly, VI does so without sacrificing precision or accuracy, presenting an overall improvement over previously published methods.
Comprehensive regulatory networks for tomato organ development based on the genome and RNAome of microTom tomato
Authors: Xue Jia-Yu , Fan Hai-Yun , Zeng Zhen , Zhou Yu-Han , Hu Shuai-Ya , Li Sai-Xi , Cheng Ying-Juan , Meng Xiang-Ru , Chen Fei , Shao Zhu-Qing , Van de Peer Yves 
Published: December 2022

AbstractMicroTom tomato has a short growth cycle and high transformation efficiency, and is a prospective model plant for studying organ development, metabolism, and plant-microbe interactions. Here, with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments, we constructed multiple gene co-expression networks, which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth, e.g., arbuscular mycorrhizal symbiosis and fruit development. Additionally, non-coding RNAs, including miRNAs, lncRNAs and circRNAs were also identified, together with their potential targets. Interacting networks between different types of non-coding RNAs (miRNA-lncRNA), and non-coding RNAs and genes (miRNA-mRNA and lncRNA-mRNA) were constructed as well. Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit. Lastly, we established a database (http://eplant.njau.edu.cn/microTomBase/) with genomic and transcriptomic data, as well as details of gene co-expression and interacting networks on microTom, and this database should be of great value to those who wants to adopt microTom as a model plant for research.
Unprecedented yet gradual nature of first millennium CE intercontinental crop plant dispersal revealed in ancient Negev desert refuse
Authors: Fuks Daniel , Melamed Yoel , Langgut Dafna , Erickson-Gini Tali , Tepper Yotam , Bar-Oz Guy , Weiss Ehud 
Published: December 2022

AbstractGlobal agro-biodiversity has resulted from processes of plant migration and agricultural adoption. Although critically affecting current diversity, crop diffusion from antiquity to the middle-ages is poorly researched, overshadowed by studies on that of prehistoric periods. A new archaeobotanical dataset from three Negev Highland desert sites demonstrates the first millennium CE’s significance for long-term agricultural change in southwest Asia. This enables evaluation of the “Islamic Green Revolution” (IGR) thesis compared to “Roman Agricultural Diffusion” (RAD), and both versus crop diffusion since the Neolithic. Among the finds, some of the earliestSolanum melongenaseeds in the Levant represent the proposed IGR. Several other identified economic plants, including two unprecedented in Levantine archaeobotany (Ziziphus jujuba, Lupinus albus), implicate RAD as the greater force for crop migrations. Altogether the evidence supports a gradualist model for Holocene-wide crop diffusion, within which the first millennium CE contributed more to global agro-diversity than any earlier period.
Drug repurposing of dopaminergic drugs to inhibit Ataxin-3 aggregation
Authors: Figueiredo Francisco , Sárkány Zsuzsa , Silva Alexandra , Martins Pedro M. , Ribeiro Sandra Macedo 
Published: December 2022

AbstractThe accumulation of mutant ataxin-3 (Atx3) in neuronal nuclear inclusions is a pathological hallmark of Machado-Joseph disease (MJD), also known as Spinocerebellar Ataxia Type 3. Decreasing the protein aggregation burden is a possible disease-modifying strategy to tackle MJD and other neurodegenerative disorders for which only symptomatic treatments are currently available. We performed a drug repurposing screening to identify inhibitors of Atx3 aggregation with known toxicological and pharmacokinetic profiles. Interestingly, dopamine hydrochloride and other catecholamines are among the most potent inhibitors of Atx3 aggregationin vitro. Our results indicate that low micromolar concentrations of dopamine markedly delay the formation of mature amyloid fibrils of mutant Atx3 through the inhibition of the earlier oligomerization steps. Although dopamine itself does not pass the blood-brain barrier, dopamine levels in the brain can be increased by low doses of dopamine precursors and dopamine agonists commonly used to treat Parkinsonian symptoms. These findings disclose a possible application of dopaminergic drugs to halt or reduce Atx3 accumulation in the brains of MJD patients.
Viability of HepG2 and MCF-7 Cells is not Correlated with Mitochondrial Bioenergetics
Authors: Doczi Judit , Karnok Noemi , Bui David , Azarov Victoria , Pallag Gergely , Nazarian Sara , Czumbel Bence , Seyfried Thomas N , Chinopoulos Christos 
Published: December 2022

ABSTRACTAlterations in metabolism is a hallmark of cancer. It is unclear, however, if oxidative phosphorylation (OXPHOS) is required for tumor cell survival. We investigated the effect of severe hypoxia, site-specific inhibition of respiratory chain (RC) components, and uncouplers on the survival of HepG2 and MCF-7 2D cultured cells. Comparable respiratory complex activities were observed in both cell lines, but HepG2 cells exhibited much higher oxygen consumption rates (OCR) and respiratory capacity than the MCF-7 cells. Significant non-mitochondrial OCR was found in MCF-7 cells that was insensitive to acute combined inhibition of complexes I and III. However, pre-treatment of either cell line with RC inhibitors for 24-72 hours abolished respective complex activities and OCRs completely, and this was associated with a time-dependent decrease in citrate synthase activity, suggesting mitophagy. HepG2 cells viability was mostly unaffected by any pharmacological treatment or severe hypoxia as temporally recorded from high-content automated microscopy. Conversely, MCF-7 cells viability exhibited strong sensitivity to CIV or CV inhibition, severe hypoxia, and uncoupling, but were only moderately affected by CI, CII and CIII inhibition. CII, CIII and CIV-inhibitor mediated MCF-7 cell death were partially abrogated by aspartate. The data show that OXPHOS activity and viability are uncorrelated in these cell lines indicating that a linkage of OXPHOS to cancer cell survival must be cell- and condition-defined.
Allosteric SHP2 Inhibition Increases Apoptotic Dependency on BCL2 and Synergizes with Venetoclax inFLT3-andKIT-Mutant AML
Authors: Popescu Bogdan , Stahlhut Carlos , Tarver Theodore C. , Wishner Sydney , Lee Bianca J. , Peretz Cheryl A. C. , Luck Cuyler , Phojanakong Paul , Serrano Juan Antonio Camara , Hongo Henry , Rivera Jose M. , Xirenayi Simayijiang , Chukinas John A. , Steri Veronica , Tasian Sarah K. , Stieglitz Elliot , Smith Catherine C. 
Published: December 2022

AbstractMutations in receptor tyrosine kinases (RTKs) FLT3 and KIT are frequent and associated with poor outcomes in acute myeloid leukemia (AML). Although FLT3 inhibitors (FLT3i) are clinically effective, remissions are short-lived due to secondary resistance characterized by acquired mutations constitutively activating the RAS/MAPK pathway. Hereby, we report pre-clinical efficacy of co-targeting SHP2, a critical node in MAPK signaling, and BCL2 in RTK-driven AML. The allosteric SHP2 inhibitor RMC-4550 suppressed proliferation of AML cell lines with FLT3 and KIT mutations, including cell lines with acquired resistance to FLT3i. We demonstrate that SHP2 inhibition unveils an Achilles’ heel of AML, increasing apoptotic dependency on BCL2 via MAPK-dependent mechanisms, including upregulation of BMF and downregulation of MCL1. Consequently, RMC-4550 and venetoclax are synergistically lethal inFLT3- orKIT-mutant AML cell lines, and in clinically relevant xenograft models. Our results provide new mechanistic rationale and preclinical evidence for co-targeting SHP2 and BCL2 in RTK-driven AML.SignificanceThere is an unmet need for effective therapies targeting the MAPK pathway to overcome resistance in RTK-driven AML. We report that pharmacologic co-inhibition of SHP2 and BCL2 has synergistic anti-leukemia activity in preclinical models of AML with FLT3 and KIT mutations and holds potential clinical utility.
Genomic analysis ofMycobacterium brumaesustains its nonpathogenic and immunogenic phenotype
Authors: Renau-Mínguez Chantal , Herrero-Abadía Paula , Sentandreu Vicente , Ruiz-Rodriguez Paula , Torrents Eduard , Chiner-Oms Álvaro , Torres-Puente Manuela , Comas Iñaki , Julián Esther , Coscolla Mireia 
Published: December 2022

AbstractM. brumaeis a rapid-growing, non-pathogenic Mycobacterium species, originally isolated from environmental and human samples in Barcelona, Spain.M. brumaeis not pathogenic and its in vitro phenotype and immunogenic properties have been well characterized. However, the knowledge of its underlying genetic composition is still incomplete. In this study, we first describe the 4 Mb genome of theM. brumaetype strain ATCC 51384T assembling PacBio reads, and second, we assess the low intraspecies variability by comparing the type strain with Illumina reads from three additional strains.M. brumaegenome is composed of a circular chromosome with a high GC content of 69.2 % and containing 3,791 CDSs, 97 pseudogenes, one prophage and no CRISPR loci.M. brumaehas shown no pathogenic potential in in vivo experiments, and our genomic analysis confirms its phylogenetic position with other non-pathogenic and rapid growing mycobacteria. Accordingly, we determined the absence of virulence related genes, such as ESX-1 locus and most PE/PPE genes, among others. Although immunogenic potential ofM. brumaewas proved to be as high asMycobacterium bovisBCG, the only mycobacteria licensed to treat cancer, the genomic content ofM. tuberculosisT cell and B cell antigens inM. brumaeis considerably lower than those ofM. bovisBCG. Overall, this work provides relevant genomic data on one of the species of the mycobacterial genus with high therapeutic potential.
Genetic estimates of the initial peopling of Polynesian islands actually reflect later inter-island contacts
Authors: Huang Yilei , Carmi Shai , Reich David , Ringbauer Harald 
Published: December 2022

SummaryThe timing of the initial peopling of the Polynesian islands remains highly debated. Suggested dates are primarily based on archaeological evidence and differ by several hundred years. Ioannidis et al. [2021] used genome-wide data from 430 modern individuals from 21 Pacific islands to obtain genetic estimates. Their results supported late settlement dates, e.g. approximately 1200 CE for Rapa Nui. However, when investigating the underlying model we found that the genetic estimator used by Ioannidis et al. [2021] is biased to be about 300 years too old. Correcting for this bias gives genetic settlement dates that are more recent than any dates consistent with archaeological records, as radiocarbon dating of human-modified artifacts shows settlement definitively earlier than the bias-corrected genetic estimates. These too-recent estimates can only be explained by substantial gene flow between islands after their initial settlements. Therefore, contacts attested by archaeological and linguistic evidence [Kirch, 2021] must have been accompanied also by demographically significant movement of people. This gene flow well after the initial settlements was not modelled by Ioannidis et al. [2021] and challenges their interpretation that carving anthropomorphic stone statues was spread during initial settlements of islands. Instead, the distribution of this cultural practice likely reflects later inter-island exchanges, as suggested earlier [Kirch, 2017].
Genetic identification and reiterated captures suggests that theAstyanax mexicanusEl Pachón cavefish population is closed and declining
Authors: Legendre Laurent , Rode Julie , Germon Isabelle , Pavie Marie , Quiviger Carla , Policarpo Maxime , Leclercq Julien , Père Stéphane , Fumey Julien , Hyacinthe Carole , Ornelas-García Patricia , Espinasa Luis , Rétaux Sylvie , Casane Didier 
Published: December 2022

AbstractThe size ofAstyanax mexicanusblind cavefish populations of North-East Mexico is a demographic parameter of great importance for investigating a variety of ecological, evolutionary and conservation issues. However, very few estimates have been obtained. For these mobile animals living in an environment difficult to explore as a whole, methods based on capture-mark-recapture are appropriate, but the feasibility of such approach and the interpretation of the results depend on several assumptions that must be carefully examined. Here, we provide evidence that minimally invasive genetic identification from captures at different time intervals can give insights on cavefish population size dynamics as well as other important demographic parameters of interest. We also provide tools to calibrate sampling and genotyping efforts necessary to reach a given level of precision. Our results suggest that the El Pachón cave population is currently very small, of an order of magnitude of a few hundreds of individuals, and is distributed in a relatively isolated area. The probable decline in population size in the El Pachón cave since the last census in 1971 raises serious conservation issues.