bluuebunny/crossref_metadata_2025_split huggingface dataset:
QUAS-R: Glutamine (Q) Uptake Assay with Single cell Resolution reveals metabolic heterogeneity with immune populations
Authors: Pelgrom Leonard , Davis Gavin , O’Shoughnessy Simon , Van Kasteren Sander , Finlay David , Sinclair Linda 
Published: October 2022

AbstractSystem level analysis of single cell data is rapidly transforming the field of immunometabolism. However, metabolic profiling of single cells and small populations by flow and mass cytometry is extremely limited by the availability of specific reagents such as antibodies and fluorescently nutrient analogues. Given the competitive demand for nutrients in pathogenic microenvironments including sites of infection, tumours and autoinflammation, there is a need to understand how and when immune cells access these nutrients. Fluorescent-tagging of nutrients is one approach to study nutrient transport but is extremely limited in its usefulness as tagging usually changes the transport characteristics and transporter specificity of the nutrient. Herein, we developed a completely new approach for single cell analysis of nutrient uptake where a fluorophore is attached to a functionalized amino acid after it has been transported across the plasma membrane and is within the cell. This in-cell biorthogonal labelling ensures that bona fide transport has been measured. System ASC transporter SLC1A5/ASCT2 transports multiple amino acids, most notably the crucial fuel glutamine, and has essential roles in supporting immune metabolism, signalling and function. This flow cytometry assay allows for rapid, sensitive, and quantitative measurement of SLC1A5-mediated uptake, which we used to interrogate the transport capacity of the complex immune subpopulations within the thymus, at a single cell resolution previously “unreachable”. Taken together, our findings provide an easy procedure to assess which cells support their function via SLC1A5 mediated uptake of amino acids in a sensitive single cell assay. This assay is a significant addition to the single-cell metabolic toolbox required to decode the metabolic landscape of complex immune microenvironments.
Heritage of ancient cultures supports conservation: a continent-wide perspective from the Eurasian steppes
Authors: Deák Balázs , Bede Ádám , Rádai Zoltán , Dembicz Iwona , Apostolova Iva , Batáry Péter , Gallé Róbert , Tóth Csaba Albert , Dózsai József , Moysiyenko Ivan I. , Sudnik-Wójcikowska Barbara , Nekhrizov Georgi , Lisetskii Fedor N. , Buryak Zhanna A. , Kis Szabolcs , Borza Sándor , Godó Laura , Bragina Tatyana M. , Smelansky Ilya , Molnár Ábel , Bán Miklós , Báthori Ferenc , Árgay Zoltán , Dani János , Valkó Orsolya 
Published: October 2022

AbstractCivilisations including ancient ones, have shaped the global ecosystems in many ways through a co-evolution of landscapes and humans. However, the cultural legacies of ancient and lost civilisations are seldom considered in conservation. Here using a continental-scale dataset containing over 1,000 data records on the localities, land cover, protection status and cultural values related to ancient steppic burial mounds (so-called ‘kurgans’), we evaluated how these iconic and widespread landmarks can contribute to grassland conservation in the Eurasian steppes, which is one of the most endangered biomes on Earth. By using Bayesian logistic generalized regressions and proportional odds logistic regressions, we aimed to reveal the potential of mounds in preserving grasslands considering landscapes with different levels of land use transformation. We also compared the conservation potential of mounds situated inside and outside protected areas and assessed whether the presence of cultural, historical or spiritual values support the maintenance of grasslands on them. We revealed that kurgans have enormous importance in preserving grasslands in transformed landscapes outside protected areas, where they can act as habitat islands, and provide an additional pillar for conservation by contributing to habitat conservation and improvement of habitat connectivity. We found that besides their steep slopes hindering ploughing, the existence of cultural, historical or religious values could almost double the chance for grassland occurrence on kurgans due to the related extensive land use and the respect of local communities. As the estimated number of steppic mounds is about 600,000 and also similar historical features exist in all continents, our results can be upscaled to a global level. Our results also suggest that an integrative socio-ecological approach in conservation might support the positive synergistic effects of conservational, landscape and cultural values.
ZNF251haploinsufficiency confers PARP inhibitors resistance inBRCA1-mutated cancer cells through activation of homologous recombination
Authors: Li Huan , Chatla Srinivas , Liu Xiaolei , Tian Zhen , Vekariya Umeshkumar , Wang Peng , Kim Dongwook , Octaviani Stacia , Lian Zhaorui , Morton George , Feng Zijie , Yang Dan , Sullivan-Reed Katherine , Childers Wayne , Yu Xiang , Chitrala Kumaraswamy Naidu , Madzo Jozef , Skorski Tomasz , Huang Jian 
Published: October 2022

AbstractPoly (ADP-ribose) polymerase inhibitors (PARPis) represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those withBRCA1/2mutations. Cancer-associatedBRCA1/2mutations disrupt DNA double-strand break (DSB) repair by homologous recombination (HR). PARP inhibitors (PARPis) have been used to trigger synthetic lethality inBRCA1/2-mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPis resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our research revealed that haploinsufficiency of theZNF251gene, which encodes zinc finger protein 251, is associated with resistance to PARPis in various breast and ovarian cancer cell lines carryingBRCA1mutations. Mechanistically, we discovered thatZNF251haploinsufficiency leads to stimulation of RAD51-mediated HR repair of DSBs in olaparib-treatedBRCA1-mutated cancer cells. Moreover, we demonstrated that a RAD51 inhibitor reversed PARPi resistance inZNF251haploinsufficient cancer cells harboringBRCA1mutations. Our findings provide important insights into the mechanisms underlying PARPis resistance by highlighting the role of RAD51 in this phenomenon.
The SARS-CoV-2 mutation landscape is shaped before replication starts
Authors: Masone Diego , Alvarez Maria Soledad , Polo Luis Mariano 
Published: October 2022

AbstractMutation landscapes and signatures have been thoroughly studied in SARS-CoV-2. Here, we analyse those patterns and link their changes to the viral replication niche. Surprisingly, those patterns look to be also modified after vaccination. Hence, by deductive reasoning we identify the steps of the coronavirus infection cycle in which those mutations initiate.
Antimicrobial Resistance, Genomic, and Public Health Insights into Enterococcus spp. from Australian Cattle
Authors: Sahibzada Shafi , Abraham Rebecca , Lee Terence , Jordan David , McMillan Kate , Mellor Glen , Duffy Lesley , O’Dea Mark , Abraham Sam , Barlow Robert 
Published: October 2022

AbstractEnterococci are opportunistic, potentially life-threatening pathogens of humans that are difficult to manage due to antimicrobial resistance. Historically, enterococci entering the food-chain through livestock have been viewed as a likely source of antimicrobial resistance in humans. Australian human-derived clinical enterococci have a propensity to be resistant to multiple classes of antimicrobials including vancomycin. Recent Australian studies involving pigs and chicken have virtually excluded these species as reservoirs of infection for resistant enterococci in humans. However, the Australian bovine population has not been similarly assessed. This study investigates the antimicrobial resistance profiles of enterococci from Australian cattle and the phylogenetic relationship between E. faecium isolated from cattle and human sepsis cases. Minimum inhibitory concentration assays were performed for E. faecium (n=343), E. faecalis (n=92), and E. hirae (n=284) against a panel of 15 antimicrobials. The majority of isolates were sensitive to all tested antimicrobials. Erythromycin resistance was most prevalent for E. faecium isolates (18.7%), daptomycin for E. faecalis (12.1%) and tetracycline for E. hirae (13.3%). Phenotypically, 1 E. faecalis was resistant to vancomycin and 9 were resistant to linezolid (E. faecium n=4, E. faecalis n=2, E. hirae n=3) but this was not confirmed with any know genotype. A subset of 67 E. faecium isolates selected for comparative phylogenetic analysis revealed that bovine isolates clustered with other livestock-derived and van-negative human isolates. In conclusion, there is a low prevalence of antimicrobial resistance amongst enterococci from Australian cattle which are unlikely to be precursor strains to vancomycin-resistant strains currently circulating in Australian hospitals.ImportanceEnterococci resistant to critically important antimicrobials such as vancomycin and linezolid are difficult to manage in health care settings. Historically, there has been the belief that livestock can act as a reservoir of resistance for human infections. Previous studies in poultry and pork have demonstrated that isolates derived from these livestock are unlikely to be precursor strains for currently circulating vancomycin resistant-Enterococci causing infection in humans. To date, there has been no study looking at the genetic similarity of bovine derived Enterococci and the relationship to human pathogenic strains. In this study we performed phenotypic and genotypic characterization of bovine derived Enterococci along with comparative phylogenetic analysis with other livestock derived and human sepsis derived E. faecium isolates. We found that while non-vancomycin resistant strain sharing occurs between hosts, cattle are unlikely to be precursor strains for vancomycin resistant human E. faecium infections.
COVID-19 vaccine antibody response is associated with side-effects, chronic health conditions, and vaccine type in a large Northern California cohort
Authors: Solomon Olivia , Adams Cameron , Horton Mary , Wong Marcus P. , Meas Michelle , Shao Xiaorong , Fedrigo Indro , Hernandez Samantha , Quach Hong L. , Quach Diana L. , Barcellos Anna L. , Coloma Josefina , Busch Michael , Harris Eva , Barcellos Lisa F. 
Published: October 2022

AbstractAs vaccines have become available for COVID-19, it is important to understand factors that may impact response. The objective of this study is to describe vaccine response in a well-characterized Northern California cohort, including differences in side-effects and antibody response by vaccine type, sex, and age, as well as describe responses in subjects with pre-existing health conditions that are known risk factors for more severe COVID-19 infection. From July 2020 to March 2021, ∼5,500 adults from the East Bay Area in Northern California were followed as part of a longitudinal cohort study. Comprehensive questionnaire data and biospecimens for COVID-19 antibody testing were collected at multiple time-points. All subjects were at least 18 years of age and members of the East-Bay COVID-19 cohort who answered questionnaires related to vaccination status and side-effects at two time-points. Three vaccines, Moderna (2 doses), Pfizer-BioNTech (2 doses), and Johnson & Johnson (single dose), were examined as exposures. Additionally, pre-existing health conditions were assessed. The main outcomes of interest were anti-SARS-CoV-2 Spike antibody response (measured by S/C ratio in the Ortho VITROS assay) and self-reporting of 11 potential vaccine side effects. When comparing both doses of the Moderna vaccine to respective doses of Pfizer-BioNTech, participants receiving the Moderna vaccine had higher odds of many reported side-effects. The same was true comparing the single-dose Johnson & Johnson vaccine to dose 2 of the Pfizer-BioNTech vaccine. The antibody S/C ratio also increased with each additional side-effect after the second dose. S/C ratios after vaccination were lower in participants aged 65 and older, and higher in females. At all vaccination timepoints, Moderna vaccine recipients had a higher S/C ratio. Individuals who were fully vaccinated with Pfizer-BioNTech had a 72.4% lower S/C ratio compared to those who were fully vaccinated with Moderna. Subjects with asthma, diabetes, and cardiovascular disease all demonstrated more than a 20% decrease in S/C ratio. In support of previous findings, we show that antibody response to the Moderna vaccine is higher than the Pfizer-BioNTech vaccine. We also observed that antibody response was associated with side-effects, and participants with a history of asthma, diabetes, and cardiovascular disease had lower antibody responses. This information is important to consider as further vaccines are recommended.
HIV positive patients on HAART continue to have a decline in renal function irrespective of Tenofovir usage: A 2-year cohort from an Indian tertiary care centre
Authors: Joshi Kavita S. , Jadhao Viplove F. , Gujarathi Rushabh Y. , Churiwala Widhi , Natu Anuya A. 
Published: October 2022

ABSTRACTContextHIV patients may undergo renal damage due to disease or nephrotoxic drugs. Tenofovir has been associated with the development of renal impairment.AimsTo study and compare trends in Creatinine Clearance (CrCl) and estimated Glomerular Filtration Rate (eGFR) in patients on Highly Active Antiretroviral Therapy (HAART) and to compare the same between patients on Tenofovir and non-Tenofovir based regimens.MethodsA cross-sectional study was conducted. We followed 244 patients for a period of 2 years. The demographic, clinical, and laboratory parameters of the patients were recorded at baseline, one year of therapy, and two years of therapy. The data was analyzed by dividing patients into Tenofovir and non-Tenofovir based groups. Statistical analysis used the Chi-square test, paired and unpaired t-tests, and Fischer’s exact test.ResultsThe mean BUN and serum creatinine in both groups were comparable at the start of the therapy. The decline in CrCl and eGFR in all patients on HAART for two years was statistically significant, irrespective of Tenofovir usage. The mean fall in eGFR in the Tenofovir group was 12.4 mL/min/1.73 m2 and in the non-Tenofovir group, 9 mL/min/1.73 m2, though the differences between eGFR and CrCl were not significant between the two groups at any point.ConclusionsEven though HAART usage has been said to slow the decline in kidney function in PLHIV, patients who receive HAART still show a statistically significant decline in renal function parameters, akin to the observations of other such studies in low-resource settings.
Utilization of Emergency Care by an East African Refugee Community Compared to Local Residents in Central Minnesota: A Cross-Sectional Study
Authors: Hughes-Scalise Abby , Ayanle Mohamed , Dakoji Srikanth 
Published: October 2022

ABSTRACTBackgroundPrevious studies on emergency service utilization by refugees have been mixed, with some showing overuse and others showing underuse relative to host populations. Much of the previous literature focuses on refugees by continent of origin, which may mask important differences within immigrant groups. Limited research has investigated emergency medicine utilization for East African refugees in the United States.MethodsThe current study investigated differences in ED service utilization for East African refugees compared to local residents at an Emergency Trauma Center (Level 2) in Central Minnesota. From a convenience sample of 48 East African refugees and 116 local residents that presented to an emergency department (ED) in Central Minnesota, survey data was collected on self-reported reasons for presenting to ED; chart review data was collected on care received at the emergency department and discharge diagnoses.ResultsLogistic regressions showed that refugees were significantly (p < .05) more likely than local residents to self-report difficulties with navigating the primary care settings as a reason for presenting to the ED, and less likely to report needing specialized care. Refugees were also significantly less likely than local residents to call their primary care provider/clinic before presenting to the ED. During the ED visit, refugees were significantly more likely than local residents to receive symptomatic care and less likely to receive advanced imaging.ConclusionWe hope these results spur additional research on this unique population, particularly related to health literacy and health equity in an emergency medicine setting for East African refugees continuing to migrate to the United States at high rates.
Cross-modal interactions at the audiovisual cocktail-party revealed by behavior, ERPs, and neural oscillations
Authors: Klatt Laura-Isabelle , Begau Alexandra , Schneider Daniel , Wascher Edmund , Getzmann Stephan 
Published: October 2022

AbstractTheories of attention argue that objects are the units of attentional selection. In real-word environments such objects can contain visual and auditory features. To understand how mechanisms of selective attention operate in multisensory environments, we created an audiovisual cocktail-party situation, in which two speakers (left and right of fixation) simultaneously articulated brief numerals. In three separate blocks, informative auditory speech was presented (a) alone or paired with (b) congruent or (c) uninformative visual speech. In all blocks, subjects localized a pre-defined numeral. While audiovisual-congruent and uninformative speech improved response times and speed of information uptake according to diffusion modeling, an ERP analysis revealed that this did not coincide with enhanced attentional engagement. Yet, consistent with object-based attentional selection, the deployment of auditory spatial attention (N2ac) was accompanied by visuo-spatial attentional orienting (N2pc) irrespective of the informational content of visual speech. Notably, an N2pc component was absent in the auditory-only condition, demonstrating that a sound-induced shift of visuo-spatial attention relies on the availability of audio-visual features evolving coherently in time. Additional analyses revealed cross-modal interactions in working memory and modulations of cognitive control. The preregistered methods and hypotheses of this study can be found athttps://osf.io/vh38g.
Changes in a new type of genomic accordion may open the pallets to increased monkeypox transmissibility
Authors: Monzón Sara , Varona Sarai , Negredo Anabel , Patiño-Galindo Juan Angel , Vidal-Freire Santiago , Zaballos Angel , Orviz Eva , Ayerdi Oskar , Muñoz-García Ana , Delgado-Iribarren Alberto , Estrada Vicente , García Cristina , Molero Francisca , Sánchez Patricia , Torres Montserrat , Vázquez Ana , Galán Juan-Carlos , Torres Ignacio , Causse del Río Manuel , Merino Laura , López Marcos , Galar Alicia , Cardeñoso Laura , Gutiérrez Almudena , Loras Cristina , Escribano Isabel , Alvarez-Argüelles Marta Elena , del Río Leticia , Simón María , Meléndez MªAngeles , Camacho Juan , Herrero Laura , Sancho Pilar Jiménez , Navarro-Rico Maria Luisa , Kuhn Jens H. , Sanchez-Lockhart Mariano , Paola Nicholas Di , Kugelman Jeffrey R. , Giannetti Elaina , Guerra Susana , García-Sastre Adolfo , Palacios Gustavo , Cuesta Isabel , Sánchez-Seco Maripaz P. 
Published: October 2022

SUMMARYThe currently expanding monkeypox epidemic is caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. In contrast to monkeypox cases caused by clade I and subclade IIa MPXV, the prognosis of current cases is generally favorable, but person-to-person transmission is much more efficient. MPXV evolution is driven by selective pressure from hosts and loss of virus–host interacting genes. However, there is no satisfactory genetic explanation using single-nucleotide polymorphisms (SNPs) for the observed increased MPXV transmissibility. We hypothesized that key genomic changes may occur in the genome’s low-complexity regions (LCRs), which are highly challenging to sequence and have been dismissed as uninformative. Using a combination of highly sensitive techniques, we determined a first high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This effort revealed significant variation in short-tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of SNPs and that LCRs are not randomly distributed.In silicoanalyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs) 153, 204, and 208 could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. Consequently, we posit that genomic studies focusing on phenotypic MPXV clade-/subclade-/lineage-/strain differences should change their focus to the study of LCR variability instead of SNP variability.
Characterization of the Doublesex/MAB-3 transcription factor DMD-9 in Caenorhabditis elegans
Authors: Godini Rasoul , Pocock Roger 
Published: October 2022

AbstractDMD-9 is a Caenorhabditis elegans Doublesex/MAB-3 Domain transcription factor of unknown function. Single-cell transcriptomics revealed that dmd-9 is highly expressed in specific head sensory neurons, with lower levels detected in non-neuronal tissues (uterine cells and spermatheca). Here, we characterized endogenous dmd-9 expression and function in hermaphrodites and males to identify potential sexually dimorphic roles. In addition, we dissected the trans- and cis-regulatory mechanisms that control DMD-9 expression in neurons. Our results show that of the 22 DMD-9-expressing neuronal reporters we analyzed, only the neuropeptide-encoding flp-19 gene is cell-autonomously regulated by DMD-9. Further, we did not identify defects in behaviors mediated by DMD-9 expressing neurons in dmd-9 mutants. We found that dmd-9 expression in neurons is regulated by four neuronal fate regulatory TFs: ETS-5, EGL-13, CHE-1, and TTX-1. In conclusion, our study characterized the DMD-9 expression pattern and regulatory logic for its control. We found that, as with other DMD TFs, DMD-9 likely acts redundantly to control neuronal development and function.