bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryptic population structure and insecticide resistance inAnopheles gambiaefrom the southern Democratic Republic of Congo
Authors: Dennis Tristan P.W. , Pescod Poppy , Barasa Sonia , Cerdeira Louise , Lucas Eric R. , Clarkson Chris S. , Miles Alistair , Asidi Alex , Manzambi Emile Z. , Metelo Emery , Zanga Josue , Nsalambi Steve N. , Irish Seth R. , Donnelly Martin James , Agossa Fiacre , Weetman David , Tezzo Francis Wat’senga 
Published: March 2024

ABSTRACTThe Democratic Republic of Congo (DRC) suffers from one of the highest malaria burdens worldwide, but information on itsAnophelesvector populations is relatively limited. Preventative malaria control in DRC is reliant on pyrethroid-treated nets, raising concerns over the potential impacts of insecticide resistance. We sampledAnopheles gambiaefrom three geographically distinct populations (Kimpese, Kapolowe and Mikalayi) in southern DRC, collecting from three sub-sites per population and characterising mosquito collections from each for resistance to pyrethroids using WHO tube bioassays. Resistance to each of three different pyrethroids was generally high inAn. gambiaewith <92% mortality in all tests, but varied between collections, with mosquitoes from Kimpese being the most resistant.Whole genome sequencing of 165An. gambiaerevealed evidence for genetic differentiation between Kimpese and Kapolowe / Mikalayi, but not between the latter two sample sites despite separation of approximately 800km. Surprisingly, there was evidence of population structure at a small spatial scale between collection subsites in Kimpese, despite separation of just tens of kilometres. Intra-population (H12) and inter-population (FST) genome scans identified multiple peaks corresponding to genes associated with insecticide resistance such as the voltage gated sodium channel (Vgsc)target site on chromosome 2L, aCyp6cytochrome P450 cluster on chromosome arm 2R, and theCyp9k1P450 gene on chromosome X. In addition, in the Kimpese subsites, the P450 redox partner geneCprshowed evidence for contemporary selection (H12) and population differentiation (FST) meriting further exploration as a potential resistance associated marker.
The Pivotal Involvement of theRespiratory burst oxidase G(SlRbohG) Gene in H2O2Production Under Stress for Proper Na+Homeostasis Regulation in Tomato
Authors: Egea I , Barragán-Lozano T , Estrada Y , Jáquez-Gutiérrez M , Plasencia FA , Atarés A , Garcia-Sogo B , Capel C , Yuste-Lisbona F , Egea-Sánchez JM , Flores FB , Angosto T , Moreno M , Lozano R , Pineda B 
Published: March 2024

ABSTRACTRegulation of sodium homeostasis is crucial for plant response to salinity conditions. Here we report on the genetic and physiological characterization of two tomato allelic mutants,sodiumgatherer1-2(sga1-2), which exhibit pronounced chlorosis and hyperhydration under salt stress. Mapping-by-sequencing revealed that mutant phenotype resulted from mutations in theSlRbohGgene, and CRISPR/Cas9 knockouts of this gene gave phenocopies of thesga1-2mutants. Physiological analyses showed thatsga1-2salt hypersensitivity is linked to an increase of Na+and water transport from roots to shoots, which explains their extreme chlorosis and hyperhydration under salinity conditions. At the molecular level,SlPIP2;12gene, an aquaporin down-regulated in the WT under salt stress, was overexpressed in thesga1-2mutants, which could enhance water transport to the shoot. Also,sga1-2mutants exhibited a significant reduction in the expression of key sodium transporters, thus modifying the normal distribution of Na+in tomato plant tissues. Furthermore, treatment of WT plants with the NADPH oxidase inhibitor DPI prevented H2O2production in response to salinity, resulting in elevated Na+accumulation in the shoot and reduced expression of theSlHKT1;2gene in root. Altogether, our results show thatSlRbohGplays a central role in salt tolerance through ROS-mediated signaling.HIGHLIGHTLoss of function of tomatoSlRbohGgene leads hypersensibility to salt stress due to increased Na+and water transport from root to shoot.
Highly conserved brain vascular receptor ALPL mediates transport of engineered viral vectors across the blood-brain barrier
Authors: Moyer Tyler C. , Hoffman Brett A. , Chen Weitong , Shah Ishan , Ren Xiao-Qin , Knox Tatiana , Liu Jiachen , Wang Wei , Li Jiangyu , Khalid Hamza , Kulkarni Anupriya S. , Egbuchulam Munachiso , Clement Joseph , Bloedel Alexis , Child Matthew , Kaur Rupinderjit , Rouse Emily , Graham Kristin , Maura Damien , Thorpe Zachary , Sayed-Zahid Ambreen , Chung Charlotte Hiu-Yan , Kutchin Alexander , Johnson Amy , Yao Johnny , Thompson Jeffrey , Pande Nilesh , Nonnenmacher Mathieu E. 
Published: March 2024

AbstractDelivery of systemically administered therapeutics to the central nervous system (CNS) is restricted by the blood-brain barrier (BBB). Bioengineered Adeno-Associated Virus (AAV) capsids have been shown to penetrate the BBB with great efficacy in mouse and non-human primate models, but their translational potential is often limited by species selectivity and undefined mechanisms of action. Here, we apply our RNA-guided TRACER AAV capsid evolution platform to generate VCAP-102, an AAV9 variant with markedly increased brain tropism following intravenous delivery in both rodents and primates. VCAP-102 demonstrates a similar CNS tropism in cynomolgus macaque, african green monkey, marmoset and mouse, showing 20- to 400-fold increased transgene expression across multiple brain regions relative to AAV9. We demonstrate that the enhanced CNS tropism of VCAP-102 results from direct interaction with alkaline phosphatase (ALPL), a highly conserved membrane-associated protein expressed on the brain vasculature. VCAP-102 interacts with human, primate and murine ALPL isoforms, and ectopic expression of ALPL is sufficient to initiate receptor-mediated transcytosis of VCAP-102 in an in vitro transwell model. Our work identifies VCAP-102 as a cross-species CNS gene delivery vector with a strong potential for clinical translation and establishes ALPL as a brain delivery shuttle capable of efficient BBB transport to maximize CNS delivery of biotherapeutics.
Forecasting Dengue Fever in Brazil Using Multimodal Data, Including Climate Data
Authors: Danko David C. , Vörösmarty Charles , Cak Anthony , Corsi Fabio , Patel Suraj , Papciak John , Wells Heather , Albanese Anthony , Mason Christopher E. , Maciel-de-Freitas Rafael , Nagy-Szakal Dorottya , O’Hara Niamh B. 
Published: March 2024

AbstractDengue fever is a major tropical disease transmitted byAedesmosquitoes. Dengue affects more than 120 countries with highly variable year to year infection rates. Despite high variability, dengue has a clear relationship to climate factors and human demography. Global trends to higher temperatures and greater disorderly urban development are increasing the scale and scope of dengue risk. Dengue has complex human immunity with 4 known serotypes that make multiple infections possible. Accurate forecasting of dengue fever would allow for appropriate interventions and improved public health outcomes. We demonstrate,GeoSeeq Dengue, a forecasting model for dengue fever in Brazil. GeoSeeq Dengue predicts dengue outbreaks monthly in 5,570 Brazilian municipalities at 1, 3, and 6 months ahead of the outbreak. Model accuracy compares favorably to a historical baseline model, making it a promising model for informing public health response. We evaluate how different types of input variables effect model accuracy and explore how this model could be adapted to other countries. This model could inform public health responses to dengue including targeting vector control programs, public health education messaging, and the newly launched dengue vaccine rollout.
Pan-UK Biobank GWAS improves discovery, analysis of genetic architecture, and resolution into ancestry-enriched effects
Authors: Karczewski Konrad J. , Gupta Rahul , Kanai Masahiro , Lu Wenhan , Tsuo Kristin , Wang Ying , Walters Raymond K. , Turley Patrick , Callier Shawneequa , Shah Nirav N. , Baya Nikolas , Palmer Duncan S. , Goldstein Jacqueline I. , Sarma Gopal , Solomonson Matthew , Cheng Nathan , Bryant Sam , Churchhouse Claire , Cusick Caroline M. , Poterba Timothy , Compitello John , King Daniel , Zhou Wei , Seed Cotton , Finucane Hilary K. , Daly Mark J. , Neale Benjamin M. , Atkinson Elizabeth G. , Martin Alicia R. 
Published: March 2024

SummaryLarge biobanks, such as the UK Biobank (UKB), enable massive phenome by genome-wide association studies that elucidate genetic etiology of complex traits. However, individuals from diverse genetic ancestry groups are often excluded from association analyses due to concerns about population structure introducing false positive associations. Here, we generate mixed model associations and meta-analyses across genetic ancestry groups, inclusive of a larger fraction of the UKB than previous efforts, to produce freely-available summary statistics for 7,266 traits. We build a quality control and analysis framework informed by genetic architecture. Overall, we identify 14,676 significant loci (p < 5 x 10-8) in the meta-analysis that were not found in the EUR genetic ancestry group alone, including novel associations for example betweenCAMK2Dand triglycerides. We also highlight associations from ancestry-enriched variation, including a known pleiotropic missense variant inG6PDassociated with several biomarker traits. We release these results publicly alongside FAQs that describe caveats for interpretation of results, enhancing available resources for interpretation of risk variants across diverse populations.
Enrichment of Rare Variants of Hemophagocytic Lymphohistiocytosis Genes in Systemic Juvenile Idiopathic Arthritis
Authors: Marques Mariana Correia , Rubin Danielle , Shuldiner Emily , Datta Mallika , Schmitz Elizabeth , Cruz Gustavo Gutierrez , Patt Andrew , Bennett Elizabeth , Grom Alexei , Foell Dirk , Gattorno Marco , Bohnsack John , Yeung Rae S. M. , Prahalad Sampath , Mellins Elizabeth , Anton Jordi , Len Claudio Arnaldo , Oliveira Sheila , Woo Patricia , Ozen Seza ,   INCHARGE Consortium, Deng Zuoming , Ombrello Michael J. 
Published: March 2024

AbstractObjectiveTo evaluate whether there is an enrichment of rare variants in familial hemophagocytic lymphohistiocytosis (HLH) genes and systemic juvenile idiopathic arthritis (sJIA) with or without macrophage activation syndrome (MAS).MethodsTargeted sequencing of HLH genes (LYST, PRF1, RAB27A, STX11, STXBP2, UNC13D) was performed in sJIA subjects from an established cohort. Sequence data from control subjects were obtainedin silico(dbGaP:phs000280.v8.p2). Rare variant association testing (RVT) was performed with sequence kernel association test (SKAT) package. Significance was defined as p<0.05 after 100,000 permutations.ResultsSequencing data from 524 sJIA cases were jointly called and harmonized with exome-derived target data from 3000 controls. Quality control operations produced a set of 481 cases and 2924 ancestrally-matched control subjects. RVT of sJIA cases and controls revealed a significant association with rare protein-altering variants (minor allele frequency [MAF]<0.01) ofSTXBP2(p=0.020), and ultra-rare variants (MAF<0.001) ofSTXBP2(p=0.007) andUNC13D(p=0.045). A subanalysis of 32 cases with known MAS and 90 without revealed significant association of rareUNC13Dvariants (p=0.0047). Additionally, sJIA patients more often carried ≥2 HLH variants than did controls (p=0.007), driven largely by digenic combinations involvingLYST.ConclusionWe identified an enrichment of rare HLH variants in sJIA patients compared with healthy controls, driven bySTXBP2andUNC13D. Biallelic variation in HLH genes was associated with sJIA, driven byLYST. OnlyUNC13Ddisplayed enrichment in patients with MAS. This suggests that HLH variants may contribute to the pathophysiology of sJIA, even without MAS.
Menopausal symptom burden as a predictor of mid- to late-life cognitive function and mild behavioral impairment symptoms: A CAN-PROTECT study
Authors: Crockford Jasper F.E. , Guan Dylan X , Einstein Gillian , Ballard Clive , Creese Bryon , Corbett Anne , Pickering Ellie , Bloomfield Adam , Roach Pamela , Smith Eric E , Ismail Zahinoor 
Published: March 2024

AbstractBackgroundRecent evidence suggests the experience of menopausal symptoms (i.e., perimenopausal symptoms) may be associated with cognitive and behavioural changes. We investigated these two relationships in a sample of post-menopausal females.DesignCross-sectional observational study.SettingParticipant data was collected from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behaviour, Function, and Caregiving in Aging (CAN-PROTECT) study.Participants896 post-menopausal female participants.MethodsMenopausal symptom burden was operationalized by summing the total number of recalled perimenopausal symptoms experienced. Cognitive function was measured using the Everyday Cognition (ECog-II) Scale, with higher scores reflecting greater severity. Mild Behavioral Impairment (MBI) was measured using the Mild Behavioral Impairment Checklist (MBI-C), with higher scores reflecting greater severity. A negative-binomial regression model examined the relationship between menopausal symptom burden and cognitive function, while a zero-inflated negative binomial regression model examined the relationship between menopausal symptom burden and MBI symptoms. Models adjusted for age, years of education, age of menopausal onset, type of menopause, and hormone therapy (HT). Age of menopausal onset and use of HT in the two associations were investigated with moderation analyses.ResultsGreater menopausal symptom burden was associated with higher ECog-II total scores (b [95% confidence interval (CI)] = 5.37 [2.85, 7.97]) and higher MBI-C total scores (b [95% CI] = 6.09 [2.50, 9.80]). Use of HT did not significantly associate with ECog-II total scores (b [95% CI] = -10.98 [-25.33, 6.35]), however, HT was significantly associated with lower MBI-C total scores (b [95% CI] = -26.90 [-43.35, -5.67]).ConclusionsMenopausal symptom burden is associated with poorer cognitive function and more MBI symptoms in mid- to late life. HT may help mitigate symptoms of MBI. These findings suggest the experience of menopause may indicate susceptibility to cognitive and behavioural changes, both markers of dementia.
Quantifying Oxygen Demand by Patients Hospitalized with COVID-19 at a Large Safety-Net Hospital Using Multiple Methodologies
Authors: Vanderburg Sky , Law Tyler , Shete Priya B. , Riviello Elisabeth D. , Hendrickson Carolyn M. , Burns Gregory D. , Jain Vivek , Lipnick Michael S. 
Published: March 2024

ABSTRACTBackgroundDuring the COVID-19 pandemic, many facilities worldwide struggled to forecast oxygen demand, which often exceeded oxygen supply to the detriment of patient care. Accurate estimates of oxygen demand by patients with COVID-19 are scarce, and proposed estimation methods have not been fully evaluated or implemented. To address this knowledge gap, oxygen demand by COVID-19 patients was calculated at a large safety-net hospital in the United States using patient consumption (demand) data, oxygen procurement (supply) data, and modeled data with a novel calculator tool.MethodsData were extracted from electronic medical records of patients admitted with COVID-19 to Zuckerberg San Francisco General Hospital (ZSFG) from March 2020 to March 2022, including every recorded peripheral oxygen saturation (SpO2) measurement as well as oxygen delivery device(s) and settings. Total patient oxygen consumption was calculated as the sum of oxygen delivery amounts for each recorded time interval during hospitalization. Oxygen delivery amounts were calculated using delivery device-specific formulas. Patient and treatment-specific factors which may impact oxygen demand were also reported. For comparison, oxygen procurement logs from the study period were reviewed to estimate supply consumed, and theOxygencalculator.comtool was used to model oxygen demand using an experimental patient population of the same size.ResultsIn total, 282,095 time points from 1,076 patients were analyzed. Two-thirds of patients received oxygen, of which 24.3% received high-flow oxygen (HFO) therapy and 16.0% received invasive mechanical ventilation (IMV) at some point. In-hospital mortality was 7.5% overall, 10.8% for patients who received oxygen, and 28.3% for patients who received IMV. The median (IQR) duration of oxygen therapy was 3.1 (0.8-8.9) days, mean (SD) oxygen flow was 5.6 (5.0) liters per minute (LPM), and mean (SD) total volume of oxygen delivered was 180,115 (510,330) liters (L) per hospitalization. Both the supply- and model-based methods overestimated oxygen consumption compared to demand estimated from patient data.ConclusionsThis study represents one of the largest cohorts of patients with COVID-19 for which oxygen demand has been calculated, including patient clinical characteristics which may help explain variations in oxygen demand. Moreover, oxygen demand was quantified using a methodology that could be applied in any setting.
Discovery of knock-down resistance in the major African malaria vectorAnopheles funestus
Authors: Odero Joel O. , Dennis Tristan P. W. , Polo Brian , Nwezeobi Joachim , Boddé Marilou , Nagi Sanjay C. , Hernandez-Koutoucheva Anastasia , Nambunga Ismail H. , Bwanary Hamis , Mkandawile Gustav , Govella Nicodem J , Kaindoa Emmanuel W. , Ferguson Heather M. , Ochomo Eric , Clarkson Chris S. , Miles Alistair , Lawniczak Mara K. N. , Weetman David , Baldini Francesco , Okumu Fredros O. 
Published: March 2024

AbstractA major mechanism of insecticide resistance in insect pests is knock-down resistance (kdr) caused by mutations in the voltage-gated sodium channel (Vgsc) gene. Despite being common in most malariaAnophelesvector species,kdrmutations have never been observed inAnopheles funestus, the principal malaria vector in Eastern and Southern Africa. While monitoring 10 populations ofAn. funestusin Tanzania, we unexpectedly found resistance to DDT, a banned insecticide, in one location. Through whole-genome sequencing of 333An. funestussamples from these populations, we found 8 novel amino acid substitutions in theVgscgene, including thekdrvariant, L976F (L1014F inAn. gambiae), in tight linkage disequilibrium with another (P1842S). The mutants were found only at high frequency in one region, with a significant decline between 2017 and 2023. Notably,kdrL976F was strongly associated with survivorship to the exposure to DDT insecticide, while no clear association was noted with a pyrethroid insecticide (deltamethrin). Further study is necessary to identify the origin and spread ofkdrinAn. funestus, and the potential threat to current insecticide-based vector control in Africa.SignificanceKnock-down resistance (kdr) mutations confer resistance to malaria vector control insecticides and pose a grave threat to malaria control. Here, we report the first discovery of kdr inAn. funestus, the principal malaria vector in East and Southern Africa. Kdr inAn. funestusconferred resistance to DDT but not deltamethrin. Based on extensive DDT contamination and unofficial usage in Tanzania, it is possible that kdr emerged because of widespread organic pollution as opposed to through public health efforts. Regardless of origin, the discovery of kdr inAn. funestusis an alarming development that warrants immediate, extensive follow-up and close surveillance to establish the origin, and extent to which it may threaten malaria control inAn. funestus.
Spaceflight causes strain dependent gene expression changes associated with lipid and extracellular matrix dysregulation in the mouse kidney in vivo
Authors: Finch Rebecca H. , Vitry Geraldine , Siew Keith , Walsh Stephen B. , Behesti Afshin , Hardiman Gary , da Silveira Willian A. 
Published: March 2024

AbstractTo explore new worlds we must ensure humans can survive and thrive in the space environment. Incidence of kidney stones in astronauts is a major risk factor associated with long term missions, caused by increased blood calcium levels due to bone demineralisation triggered by microgravity and space radiation. Transcriptomic changes have been observed in other tissues during spaceflight, including the kidney. We analysed kidney transcriptome patterns in two different strains of mice flown on the International Space Station, C57BL/6J and BALB/c. Here we show a link between spaceflight and transcriptome patterns associated with dysregulation of lipid and extracellular matrix metabolism and altered transforming growth factor-beta signalling. A stronger response was seen in C57BL/6J mice than BALB/c. Genetic differences in hyaluronan metabolism between strains may confer protection against extracellular matrix remodelling through downregulation of epithelial-mesenchymal transition. We intend for our findings to contribute to development of new countermeasures against kidney disease in astronauts and people here on Earth.
An unsupervised deep learning framework encodes super-resolved image features to decode bacterial cell cycle
Authors: Griffié Juliette , Zhang Chen , Denereaz Julien , Pham Thanh-An , Weissbart Gauthier , Sieben Christian , Lambert Ambroise , Veening Jan-Willem , Manley Suliana 
Published: March 2024

AbstractSuper-resolution microscopy can resolve cellular features at the nanoscale. However, increased spatial resolution comes with increased phototoxicity, and reduced temporal resolution. As a result, studies that require the highest spatial resolutions often rely on static or fixed images, lacking dynamic information. This is particularly true of bacteria, whose lateral dimensions approach the scale of the diffraction limit. In this work, we present Enso, a method based on unsupervised machine learning to recover bacterial cell cycle and cell type information from static single molecule localization microscopy (SMLM) images, whilst retaining nanoscale spatial resolution. Enso uses single-cell images as input, and orders cells according to their spatial pattern progression, ultimately linked to the cell cycle. Our method requires noa prioriknowledge or categories, and is validated on both simulated and user-annotated experimental data.
BinDash 2.0: New MinHash Scheme Allows Ultra-fast and Accurate Genome Search and Comparisons
Authors: Zhao Jianshu , Zhao Xiaofei , Pierre-Both Jean , Konstantinidis Konstantinos T. 
Published: March 2024

AbstractMotivationComparing large number of genomes in term of their genomic distance is becoming more and more challenging because there is an increasing number of microbial genomes deposited in public databases. Nowadays, we may need to estimate pairwise distances between millions or even billions of genomes. Few softwares can perform such comparisons efficiently.ResultsHere we update the multi-threaded software BinDash by implementing several new MinHash algorithms and computational optimization (e.g. Simple Instruction Multiple Data, SIMD) for ultra-fast and accurate genome search and comparisons at trillion scale. That is, we implemented b-bit one-permutation rolling MinHash with optimal/faster densification with SIMD. Now with BinDash 2, we can perform 0.1 trillion (or ∼10^11) pairs of genome comparisons in about 1.8 hours on a descent computer cluster or several hours on personal laptops, a ∼50% or more improvement over original version. The ANI (average nucleotide identity) estimated by BinDash is well correlated with other accurate but much slower ANI estimators such as FastANI or alignment-based ANI. In line with the findings from comparing 90K genomes (∼10^9 comparisons) via FastANI, the 85% ∼ 95% ANI gap is consistent in our study of ∼10^11 prokaryotic genome comparisons via BinDash2, which indicates fundamental ecological and evolutionary forces keeping species-like unit (e.g., > 95% ANI) together.Availability and implementationBinDash is released under the Apache 2.0 license at:https://github.com/zhaoxiaofei/bindashContactkostas.konstantinidis@gatech.eduSupplementary informationSupplementary data are available at Bioinformatics online.