bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure toP. falciparuminfected mosquito bites
Authors: Lapidus Sarah , Goheen Morgan M. , Sy Mouhamad , Deme Awa B. , Ndiaye Ibrahima Mbaye , Diedhiou Younous , Mbaye Amadou Moctar , Hagadorn Kelly A. , Sene Seynabou Diouf , Pouye Mariama Nicole , Thiam Laty Gaye , Ba Aboubacar , Guerra Noemi , Mbengue Alassane , Raduwan Hamidah , Vigan-Womas Inés , Parikh Sunil , Ko Albert I. , Ndiaye Daouda , Fikrig Erol , Chuang Yu-Min , Bei Amy K. 
Published: April 2024

AbstractBackgroundMeasuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure toAnophelesmosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected withP. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO.MethodsWe tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with knownP. falciparuminfection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay.ResultsAgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinicalP. falciparuminfection and declined 3 months after infection.DiscussionReactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes inP. falciparum-infected mosquito exposure.
A Natural History ofNAA15-related Neurodevelopmental Disorder Through Adolescence
Authors: Makwana Rikhil , Christ Carolina , Patel Rahi , Marchi Elaine , Harpell Randie , Lyon Gholson J. 
Published: April 2024

AbstractNAA15 is a member of the NatA N-terminal acetyltransferase complex, which also includes the NAA10 enzymatic sub-unit. Individuals with variants in theNAA15coding region developNAA15-related neurodevelopmental syndrome, which presents with a wide array of manifestations that affect the heart, brain, musculoskeletal system, and behavioral and cognitive development. We tracked a cohort of 27 participants (9 females and 18 males) over time, each with a pathogenicNAA15variant, and administered the Vineland-3 assessment to assess their adaptive functioning. We found that the cohort performed significantly worse compared to the normalized Vineland values. On average, females performed better than males, and they performed significantly better on the Motor Domain and Fine Motor Sub-Domain portions of the assessment. Over time, females showed a decrease in adaptive functioning, with the decline being especially correlated at the Coping, Domestic, and Fine motor sub-domains. Males (after excluding one outlier) showed a moderate positive correlation between age and ABC standard score. Ultimately, additional longitudinal data should be collected to determine the validity of the between sex-differences and to better understand the change in adaptive behavioral outcomes of individuals withNAA15-neurodevelopmental disorder as they age.
Nausea and Gastric Myoelectrical Activity are Influenced by Hormonal Contraception in Chronic Gastroduodenal Disorders
Authors: Lim Alexandria H , Varghese Chris , Sebaratnam Gabrielle , Schamberg Gabriel , Calder Stefan , Gharibans Armen , Andrews Christopher N , Daker Charlotte , Foong Daphne , Ho Vincent , Wise Michelle R , O’Grady Greg 
Published: April 2024

AbstractBackgroundChronic gastroduodenal disorders such as chronic nausea and vomiting syndrome (CNVS), functional dyspepsia (FD) and gastroparesis, are more prevalent among young women, many of whom are hormonal contraception users. We aimed to evaluate the effects of hormonal contraception on symptom severity and gastric myoelectrical activity in people with chronic gastroduodenal disorders.MethodsThis analysis was conducted on a large international cohort of patients who met Rome IV criteria for CNVS or FD and had undergone body surface gastric mapping using Gastric Alimetry (Alimetry, New Zealand). Symptoms were continuously reported on 0-10 Likert scales using a validated symptom logging app.Results127 people were included: 43 females using hormonal contraception, 30 premenopausal females not using hormonal contraception, 30 postmenopausal females, and 24 males. Premenopausal females who used hormonal contraception had higher nausea scores than non-users (3.80 [IQR 2.00-5.42] vs 2.25 [0.20-4.43]; p<0.05), particularly when using the combined oral contraceptive pill (COCP) with hormone-free intervals compared to continuous use (5.20 [4.30-6.00] vs. 2.40 [1.70-3.80], p=0.02). Premenopausal women were more symptomatic than postmenopausal women and men (p<0.001). The Principal Gastric Frequency was higher in hormonal contraception users (median 3.1 cpm [IQR 3.00-3.30] vs. 3.00 cpm [2.90-3.10], p<0.001), and highest in users of progestogen-only formulations (p<0.02).ConclusionWomen with gastrointestinal disorders on hormonal contraception experience increased nausea in comparison to non-users of hormonal contraception, with substantial variation in nausea severity dependent on contraceptive type. Hormonal contraception users also demonstrated modified gastric electrophysiology. Women with chronic gastroduodenal symptoms should be asked about their use of hormonal contraception and non-hormonal contraceptive alternatives trialled as a means to reduce symptoms.
Herbivory can increase plant fitness via reduced interspecific competition – evidence from models and mesocosms
Authors: Böttner Laura , Dudenhausen Fabio , Nouere Sara , Malacrinò Antonino , Schäfer Martin , Koene Joris M. , Huber Meret , Xu Shuqing 
Published: April 2024

AbstractHerbivores are generally considered to reduce plant fitness. However, as in natural communities herbivores often feed on several competing plant species, herbivores can also increase plant fitness by reducing interspecific competition among plants. In this study, we developed a testable model to predict plant fitness in the presence of an interspecific competitor and an herbivore that feeds on both plant species. Our model allows to predict at which herbivore and competitor densities the focal species will benefit from herbivory. This can be estimated by quantifying the effects of the herbivore on the fitness of the focal plant and on its competitor, and by estimating the levels of intra- and interspecific competition in a pair-wise fashion, respectively. We subsequently validated the model in indoor microcosms using three interacting species: an aquatic macrophyte (the giant duckweedSpirodela polyrhiza), its native competitors (green algae), and its native herbivore (the pond snailLymnaea stagnalis). Additional outdoor mesocosm experiments supported our model under natural conditions. Together, this study provides a conceptual framework to understand how herbivores shape plant fitness in a community context.
Alternative oxidase alleviates mitochondrial oxidative stress during limited nitrate reduction inArabidopsis thaliana
Authors: Otomaru Daisuke , Ooi Natsumi , Monden Kota , Suzuki Takamasa , Noguchi Ko , Nakagawa Tsuyoshi , Hachiya Takushi 
Published: April 2024

AbstractThe conversion of nitrate to ammonium, i.e., nitrate reduction, is a major consumer of reductants in plants. Previous studies have reported that the mitochondrial alternative oxidase (AOX) is upregulated under limited nitrate reduction conditions, including no/low nitrate or when ammonium is the sole nitrogen (N) source. Electron transfer from ubiquinone to AOX bypasses the proton-pumping complexes III and IV, thereby consuming reductants efficiently. Thus, upregulated AOX under limited nitrate reduction may dissipate excessive reductants and thereby attenuate oxidative stress. Nevertheless, so far there is no firm evidence for this hypothesis due to the lack of experimental systems to analyze the direct relationship between nitrate reduction and AOX. We therefore developed a novel culturing system forA. thalianathat manipulates activities of nitrate reduction and AOX separately without causing N starvation, ammonium toxicity, and lack of nitrate signal. Using this system we examined genome-wide gene expression and plant growth to better understand the relationship between AOX and nitrate reduction. Here we show that AOX alleviates mitochondrial oxidative stress and sustains plant growth under limited nitrate reduction.
Fmp40 ampylase regulates cell survival upon oxidative stress by controlling Prx1 and Trx3 oxidation
Authors: Masanta Suchismita , Wiesyk Aneta , Panja Chiranjit , Pilch Sylwia , Ciesla Jaroslaw , Sipko Marta , De Abhipshita , Enkhbaatar Tuguldur , Maslanka Roman , Skoneczna Adrianna , Kucharczyk Roza 
Published: April 2024

AbstractReactive oxygen species (ROS), play important roles in cellular signaling, nonetheless are toxic at higher concentrations. Cells have many interconnected, overlapped or backup systems to neutralize ROS, but their regulatory mechanisms remain poorly understood. Here, we reveal an essential role for mitochondrial AMPylase Fmp40 from budding yeast in regulating the redox states of mitochondrial 1-Cys peroxiredoxin, Prx1, which is the only protein shown to neutralize H2O2with the oxidation of the mitochondrial glutathione and Trx3, thioredoxin, directly involved in the reduction of Prx1. Deletion ofFMP40impacts a cellular response to H2O2treatment that leads to programmed cell death (PCD) induction and an adaptive response involving up or down regulation of genes encoding, among others the catalase Cta1, PCD inducing factor Aif1, and mitochondrial redoxins Trx3 and Grx2. This ultimately perturbs the reduced glutathione and NADPH cellular pools. We further demonstrated that Fmp40 AMPylates Prx1, Trx3, and Grx2in vitroand interacts with Trx3in vivo. AMPylation of the threonine residue 66 in Trx3 is essential for this protein’s proper endogenous level of and its precursor forms’ maturation under oxidative stress conditions. Additionally, we showed the Grx2 involvement in the reduction of Trx3in vivo. Taken together, Fmp40, through control of the reduction of mitochondrial redoxins, regulates the hydrogen peroxide, GSH and NADPH signaling influencing the programmed cell death execution.Graphical abstract
Systematic genome-wide discovery of host factors governing bacteriophage infectivity
Authors: Chitboonthavisuk Chutikarn , Martin Cody , Huss Phil , Peters Jason M. , Anantharaman Karthik , Raman Srivatsan 
Published: April 2024

AbstractBacterial host factors regulate the infection cycle of bacteriophages. Except for some well-studied host factors (e.g., receptors or restriction-modification systems), the contribution of the rest of the host genome on phage infection remains poorly understood. We developed ‘PHAGEPACK’, a pooled assay that systematically and comprehensively measures each host gene’s impact on phage fitness. PHAGEPACK combines CRISPR interference with phage packaging to link host perturbation to phage fitness during active infection. Using PHAGEPACK, we constructed a genome-wide map of genes impacting T7 phage fitness in permissiveE. coli, revealing pathways previously unknown to affect phage packaging. When applied to the non-permissiveE. coliO121, PHAGEPACK identified pathways leading to host resistance; their removal increased phage susceptibility up to a billion-fold. Bioinformatic analysis indicates phage genomes carry homologs or truncations of key host factors, potentially for fitness advantage. In summary, PHAGEPACK offers valuable insights into phage-host interactions, phage evolution, and bacterial resistance.
Adverse Event Comparison between Glucagon-like Peptide-1 Receptor Agonists and Other Anti-Obesity Medications Following Bariatric Surgery
Authors: Samuels Jason M , Niswender Kevin , Roumie Christianne L. , Self Wesley , Holzman Michael , Spann Matthew , Flynn C. Robb , Ye Fei , Irlmeier Rebecca , Funk Luke M. , Patel Mayur 
Published: April 2024

AbstractIntroductionThe safety of Glucagon-like Peptide 1 Receptor Agonists (GLP1RAs) following bariatric surgery remains largely unknown. This study aims to compare the incidence of adverse events (AEs) with GLP1RAs and other anti-obesity medications (AOMs) after bariatric surgery.MethodsThis single-center retrospective cohort included patients (ages 16-65) if they met the following criteria: underwent laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Subjects were categorized as users of ‘FDA-approved’ or ‘off label’ AOMs or GLP1RAs AOMs if documented as receiving the medication on the cohort entry date or after. Non-GLP1RA AOMs were Phentermine, Orlistat, Topiramate, Canagliflozin, Dapagliflozin, Empagliflozin, Naltrexone, Bupropion/Naltrexone, and Phentermine/Topiramate. GLP1RAs AOMs included: Semaglutide, Dulaglutide, Exenatide, Liraglutide. Primary outcome was AEs incidence. Logistic regression was used to determine the association of AOM exposure with AEs.ResultsWe identified 599 patients meeting inclusion criteria (83% female, median 47.8 years old (IQR 40.9 – 55.4). Median surgery to AOM duration was 30 months (IQR 0 – 62). GLP1RAs were not associated with higher odds of AEs (adjusted Odds Ratio, (aOR) 1.1, [95% CI 0.5 – 2.6] and 1.1 [95% CI 0.6 – 2.3] for GLP1RA versus FDA-approved and ‘Off-Label’ AOMs, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01. [95% CI 0.0 – 0.01], p<0.001).ConclusionGLP1RAs were not associated with an increased risk of AEs compared to non-GLP1RA AOMs in patients who previously underwent bariatric surgery. Prospective studies are needed to identify the optimal timeframe for initiation of GLP1RA.
The SPFH complex HflK-HflC regulates aerobic respiration in bacteria
Authors: Perez-Lopez Maria Isabel , Lubrano Paul , Angelidou Georgia , Glatter Timo , Paczia Nicole , Link Hannes , Sourjik Victor 
Published: April 2024

ABSTRACTThe bacterial HflK-HflC membrane complex is a member of the highly conserved SPFH protein family, which is found throughout all domains of life and includes eukaryotic stomatins, flotillins, and prohibitins. These proteins organize cell membranes and are involved in various processes. However, the exact physiological functions of most bacterial SPFH proteins remain unclear. Here, we report that the HflK-HflC complex inEscherichia coliis required for growth under high aeration. The absence of this complex causes an aerobic growth defect due to a reduced abundance of IspG, a crucial enzyme in the isoprenoid biosynthetic pathway. This reduction leads to lower levels of ubiquinone, reduced respiration, lower ATP levels, and misregulated expression of respiratory genes. The regulation of aerobic respiration by the HflK-HflC complex resembles the mitochondrial respiratory defects caused by prohibitin mutations in mammalian and yeast cells, suggesting a functional commonality between these bacterial and eukaryotic SPFH proteins.
Accelerating antimalarial drug discovery with a new high-throughput screen for fast-killing compounds
Authors: Sakura Takaya , Ishii Ryuta , Yoshida Eri , Kita Kiyoshi , Kato Teruhisa , Inaoka Daniel Ken 
Published: April 2024

AbstractThe urgent need for rapidly acting compounds in the development of antimalarial drugs underscores the significance of such compounds in overcoming resistance issues and improving patient adherence to antimalarial treatments. The present study introduces a high-throughput screening (HTS) approach using 1536-well plates, employingPlasmodium falciparumlactate dehydrogenase (PfLDH) combined with nitroreductase (NTR) and fluorescent probes to evaluate inhibition of the growth of the asexual blood stage of malaria parasites. This method was adapted to efficiently measure the parasite reduction ratio (PRR) in a 384-well plate format, streamlining the traditionally time-consuming screening process. By successfully screening numerous compounds, this approach identified fast-killing hits early in the screening process, addressing challenges associated with artemisinin-based combination therapies. The high-throughput PRR method is expected to be of value in continuously monitoring fast-killing properties during structure-activity relationship studies, expediting the identification and development of novel, rapidly acting antimalarial drugs within phenotypic drug discovery campaigns.
Border quarantine, vaccination and public health measures to mitigate the impact of COVID-19 importations: a modelling study
Authors: Lydeamore Michael J , Zachreson Cameron , Conway Eamon , Shearer Freya M , Baker Christopher M , Ross Joshua V , Miller Joel C , McCaw James M , Geard Nicholas , McVernon Jodie , Price David J 
Published: April 2024

AbstractWe developed a flexible infectious disease model framework that combines a detailed individual-based model of arrival pathways (quarantine model) and an individual-based model of the arrivals environment (community model) to inform border risk assessments. The work was motivated by Australia’s desire to safely increase international arrival volumes, which had been heavily constrained since early 2020 as a result of the COVID-19 pandemic. These analyses supported decisions on quarantine and border policy in the context of the Australian government’s national reopening plan in late 2021.The quarantine model provides a detailed representation of transmission within quarantine and time-varying infectiousness and test sensitivity within individuals, to characterise the likelihood and infectiousness of breaches from quarantine. The community model subsequently captures the impact these infectious individuals have in the presence of varying vaccination coverage, arrival volumes, public health and social measures (PHSMs) and test-trace-isolate-quarantine system effectiveness in the Australian context.Our results showed that high vaccination coverage would be required to safely reopen with support from ongoing PHSMs, and quarantine pathways have minimal impact on infection dynamics in the presence of existing local transmission. The modelling pipeline we present can be flexibly adapted to a range of scenarios and thus provides a useful framework for generating timely risk assessments in the event of future pandemics.
Eye care practitioners and falls prevention: protocol for a scoping review
Authors: Chen Jingyi , Alam Khyber , Lee Si Ye , Hill Anne-Marie 
Published: April 2024

AbstractIntroductionFalls are the leading cause of injury in older adults and can lead to substantial costs for the individual and society. Eye care practitioners in the community provide services for a large proportion of the older adult population and can play a key role in falls prevention, however it is unclear whether they are implementing evidence-based recommendations in practice. The aim of this scoping review is to map and synthesise the current evidence for community-based eye care practitioners translating falls prevention evidence into clinical practice.Methods and analysisThe study will use the framework by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Studies that have been published in English from 1990 to current on the topic of eye care practitioners and falls prevention in older adults will be searched on MEDLINE, Embase, and CINAHLPlus databases. Grey literature will be searched using Web of Science and OpenMD. The titles and abstracts of results will be screened against the inclusion criteria and full texts will be analysed. Data from final included articles will be extracted by two independent reviewers using a tool created according to the Joanna Briggs Institute guidelines. The World Falls Guidelines will be used as a framework for data mapping. Results will be charted, collated, and summarised narratively.Ethics and disseminationIt is anticipated that the results from this scoping review will highlight any gaps in the literature regarding eye care practitioner awareness and implementation of falls prevention guidelines and inform future research and clinical recommendations. Ethics approval is not required. Findings will be submitted to a peer-reviewed journal for publication.
A new targeting motif for endoplasmic reticulum surface proteins
Authors: Arad Sivan , Suseendran Parkesh , Ravid Shani , Peleg Yoav , Ben-Dor Shifra , Fidel Elena , Olender Tsviya , Wang Xiaofeng , Schuldiner Maya , Fenech Emma J 
Published: April 2024

AbstractThe Endoplasmic Reticulum (ER) is the entry site to the secretory pathway, serving as the targeting destination for ∼30% of the proteome. The mechanisms for targeting soluble or integral membrane secretory pathway proteins are well-studied. However, it is currently unknown how the tens of ER surface proteins (SuPs), central for organelle function, reach the outer leaflet of the membrane. It was previously shown that an amphipathic helix (AH) from the Brome mosaic virus protein 1a, is both necessary and sufficient for targeting to the ER surface in baker’s yeast. We therefore utilized this helix as a model substrate and performed a high-content screen to uncover factors that affect SuP targeting. Our results suggest a role for membrane lipid composition in targeting specificity. To see if the presence of an AH is a more general mechanism for SuP targeting, we searched for their presence within SuPs of both yeast and humans. Five endogenous yeast SuPs contained AHs, and of these four were sufficient for ER localization. Moreover, the presence of an AH was conserved to human SuP orthologs. By altering helix features we determine the parameters that affect this new targeting motif. Hence our work demonstrates how specific properties of AHs encode affinity for the ER membrane. More globally, understanding how SuPs are targeted correctly takes us a step forward in determining the underlying mechanisms of cellular localization and secretory pathway functions.The authors declare that they have no conflict of interest.