bluuebunny/crossref_metadata_2025_split huggingface dataset:
Putting the Asymmetric Response Concept to the test: modeling multiple stressor exposure and release in a stream food web
Authors: Kuppels Annabel , Bayat Helena S. , Gillmann Svenja M. , Schäfer Ralf B. , Vos Matthijs 
Published: July 2024

ABSTRACTCommunities in stream ecosystems often respond asymmetrically to increase and release of stressors, as indicated by slow and incomplete recovery. The Asymmetric Response Concept (ARC) posits that this is due to a shift in the relative importance of three mechanisms: tolerance, dispersal, and biotic interactions. In complex natural communities, these mechanisms may produce alternative outcomes through poorly understood indirect effects. To understand how the three mechanisms respond to different temporal stressor scenarios, we studied multiple scenarios using a stream food web model. We asked the following questions: Do groups of species decline as expected on the basis of individual tolerance rankings derived from laboratory experiments when they are embedded in a complex dynamic food web? Does the response of ecosystem function match that of communities? To address these questions, we aggregated data on individual tolerances at the level of functional groups and studied how single and multiple stressors affect food web dynamics and nutrient cycling. Multiple stressor scenarios involved different intensities of salt and temperature increase. Functional groups exhibited a different relative tolerance ranking between the laboratory and dynamic food web contexts. Salt as a single stressor had only minor and transient effects at low level but led to the loss of one or more functional groups at high level. In contrast, high temperature, alone or in combination with salt, caused the loss of functional groups at all tested levels. Patterns often differed between the response of communities and ecosystem function. We discuss our findings with respect to the ARC.Graphical Abstract
Sleep homeostasis in a naturalistic setting
Authors: Ujma Péter P. , Bódizs Róbert 
Published: July 2024

AbstractSleep, especially NREM sleep depth is homeostatically regulated, as sleep pressure builds up during wakefulness and diminishes during deep sleep. Previous evidence from this phenomenon, however, mainly stems from experimental studies which may not generalize to an ecologically valid setting. In the current study, we used a dataset of 246 individuals sleeping for at least seven nights each with a mobile EEG headband according to their ordinary daily schedule to investigate the effect of time spent in wakefulness on sleep characteristics. Increased time in wakefulness prior to sleep was associated with decreased sleep onset latency, increased sleep efficiency, a larger percentage of N3 sleep, and higher delta activity. Moreover, increased sleep pressure resulted in an increase in both the slope and the intercept of the sleep EEG spectrum. As predicted, PSD effects were most prominent in the earliest hours of sleep. Our results demonstrate that experimental findings showing increased sleep depth after extended wakefulness generalize to ecologically valid settings, and that time spent awake is an important determinant of sleep characteristics on the subsequent night. Our findings are evidence for the efficacy of sleep restriction, a behavioral technique already widely used in clinical settings, as a simple but powerful method to improve the objective quality of sleep in those with sleep problems.
Gene expression asymmetry in Parkinson’s Disease; variation ofCCTandBEXgene expression levels are correlated with hemisphere specific severity
Authors: Pierce Steven E. , van der Schans Edwin J.C. , Ensink Elizabeth , Coetzee Gerhard A. 
Published: July 2024

AbstractParkinson’s Disease (PD) develops unilaterally, which may be related to brain hemispheric differences in gene expression. Here we measured bulk RNA-seq levels in neuronal nuclei obtained from prefrontal cortex postmortem brain samples from males and females with PD and from healthy controls. Left and right hemispheres from each brain were related the side of symptom onset and compared. We employed twoa prioriapproaches; first we identified genes differentially expressed between PD and controls and between left vs right PD brain hemispheres. Second, we examined the presence of, and correlates to, variable asymmetry seen in candidate PD differentially expressed genes. We found large variation among individuals with PD, and PD stratification by gene expression similarity was required for patterns of genetic asymmetry to emerge. For a subset of PD brains, hemispherical variation ofCCTandBEXgene levels correlated with the side of PD symptom onset.
Response of photosynthetic efficiency to short-term fluctuating light and cold in tomato
Authors: Rayaprolu Laavanya , Jayasankar Keshav , Aarts Mark G. M. , Harbinson Jeremy 
Published: July 2024

AbstractClimate-resilient crops are crucial for meeting global food demand and increasing crop productivity. Photosynthesis, a crucial process, is impacted by environmental changes such as temperature and irradiance. Photosynthesis and stomatal opening often lag behind these changes, resulting in a loss in Light Use Efficiency (LUE). Temperature variations also affect photosynthesis, with a decrease below the optimal threshold resulting in a decrease in photosynthetic efficiency. To enhance photosynthetic LUE, understanding plant responses to environmental changes is essential. This study examines the short-term responses of four tomato genotypes to irradiance fluctuations using chlorophyll fluorescence and the effects of transient cold stress. The results show genotype-to-genotype variation in the maximum quantum efficiency of PSII, the kinetics of the quantum efficiency of PSII’s response to step changes in irradiance, and steady-state values of ΦPSII, which is used as a stand-in for photosynthetic efficiency. The control conditions were measured at 24°C and the cold stress conditions at 14°C. The fact that ΦPSII responds dynamically to step decrease and increase in irradiance and how cold impacts these responses illustrates the way tomato genotypes are impacted by cold stress. It also reveals how the genotypes adapt to cold exposure and recover once the cold stress is reversed.HighlightThis study investigates the adaptation and recovery of four tomato genotypes to irradiance fluctuations and transient cold stress, highlighting the importance of climate-resilient crops for food demand.
Microglia mediate the early-life programming of adult glucose control
Authors: Valdearcos M , McGrath ER , Brown Mayfield SM , Folick A , Cheang RT , Li L , Bachor TP , Lippert RN , Xu AW , Koliwad SK 
Published: July 2024

AbstractMammalian glucose homeostasis is, in part, nutritionally programmed during early neonatal life, a critical window for the formation of synapses between hypothalamic glucoregulatory centers. Although microglia are known to prune synapses throughout the brain, their specific role in refining hypothalamic glucoregulatory circuits remains unknown. Here, we show that microglia in the mediobasal hypothalamus (MBH) of mice actively engage in synaptic pruning during early life. Microglial phagocytic activity is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In particular, we show that microglia refine perineuronal nets (PNNs) within the neonatal MBH. Indeed, transiently depleting microglia before weaning (P6-16), but not afterward (P21-31), remarkably increased PNN abundance in the MBH. Furthermore, mice lacking microglia only from P6-16 had glucose intolerance due to impaired glucose-responsive pancreatic insulin secretion in adulthood, a phenotype not seen if microglial depletion occurred after weaning. Viral retrograde tracing revealed that this impairment is linked to a reduction in the number of neurons in specific hypothalamic glucoregulatory centers that synaptically connect to the pancreatic β-cell compartment. These findings show that microglia facilitate synaptic plasticity in the MBH during early life through a process that includes PNN refinement, to establish hypothalamic circuits that regulate adult glucose homeostasis.
Benchmarking for genotyping and imputation using degraded DNA for forensic applications across diverse populations
Authors: Zavala Elena I. , Rohlfs Rori V. , Moorjani Priya 
Published: July 2024

AbstractAdvancements in sequencing and laboratory technologies have enabled forensic genetic analysis on increasingly low quality and degraded DNA samples. However, existing computational methods applied to genotyping and imputation for generating DNA profiles from degraded DNA have not been tested for forensic applications. Here we simulated sequencing data of varying qualities– coverage, fragment lengths, and deamination patterns–from forty individuals of diverse genetic ancestries. We used this dataset to test the performance of commonly used genotype and imputation methods (SAMtools, GATK, ATLAS, Beagle, and GLIMPSE) on five different SNP panels (MPS- plex, FORCE, two extended kinship panels, and the Human Origins array) that are used for forensic and population genetics applications. For genome mapping and variant calling with degraded DNA, we find use of parameters and methods (such as ATLAS) developed for ancient DNA analysis provides a marked improvement over conventional standards used for next generation sequencing analysis. We find that ATLAS outperforms GATK and SAMtools, achieving over 90% genotyping accuracy for the four largest SNP panels with coverages greater than 10X. For lower coverages, decreased concordance rates are correlated with increased rates of heterozygosity. Genotype refinement and imputation improve the accuracy at lower coverages by leveraging population reference data. For all five SNP panels, we find that using a population reference panel representative of worldwide populations (e.g., the 1000 Genomes Project) results in increased genotype accuracies across genetic ancestries, compared to ancestry-matched population reference panels. Importantly, we find that the low SNP density of commonly used forensics SNP panels can impact the reliability and performance of genotype refinement and imputation. This highlights a critical trade-off between enhancing privacy by using panels with fewer SNPs and maintaining the effectiveness of genomic tools. We provide benchmarks and recommendations for analyzing degraded DNA from diverse populations with widely used genomic methods in forensic casework.HighlightsBiallelic SNP panels: >92% genotyping accuracy for 10X data with ATLASDegraded DNA impacts accuracy under sequencing depth of 10X coverageHigher accuracies across genetic ancestries achieved with a diverse reference panelLeveraging population reference data is not applicable for small SNP panelsTrade-off between genotype accuracy and privacy when considering SNP panel size
Machine learning-based forecasting of daily acute ischemic stroke admissions using weather data
Authors: Santhanam Nandhini , Kim Hee E. , Rügamer David , Bender Andreas , Muthers Stefan , Cho Chang Gyu , Alonso Angelika , Szabo Kristina , Centner Franz-Simon , Wenz Holger , Ganslandt Thomas , Platten Michael , Groden Christoph , Neumaier Michael , Siegel Fabian , Maros Máté E. 
Published: July 2024

AbstractBackgroundIn the midst of the emerging climate crisis, healthcare providers lack locally validated, disease-specific surveillance models. Stroke, a significant contributor to the global disease burden, has been linked to climate change. Therefore, we developed and benchmarked machine learning (ML) models based on locoregional weather systems to forecast the number of daily acute ischemic stroke (AIS) admissions.MethodsAIS patients diagnosed between 2015 and 2021 at the tertiary University Medical Center (UMC) Mannheim, Germany were extracted from the local data integration center and geospatially matched to weather data from the German Weather Service (DWD) based on the clinic’s, patients’ home and closest tower’s locations at the time of admission. Statistical- (Poisson), boosted generalized additive model (GAM), support vector machines (SVR), and tree-based models including random forest (RF) and extreme gradient boosting (XGB) were evaluated in regression settings within time-stratified nested cross-validation setup (training-validation: 2015-2020, test set: 2021) to predict the number of daily AIS admissions.FindingsThe cohort included 7,914 AIS patients (4,244 male, 53·6%). XGB showed the best test performance with lowest mean absolute error (MAE) of 1·21 cases/day. Maximum air pressure was identified as the top predictive variable. Shapley additive explanations analyses revealed that temperature extremes of extended cold-(lag-3 minimum temperature <-2 °C; minimum perceived temperature <-1·4 °C) and hot stressors (lag-7 minimum temperature >15 °C), as well as stormy conditions (lag-1 and lag-2 maximum wind gust >14 m/s and speed >10·4 m/s), increased stroke incidences substantially with distinct seasonal associations.InterpretationML models can sufficiently forecast AIS admissions based on weather patterns allowing for improved resource allocation and preparedness.
Costs of typhoid vaccination for international travelers from the United States
Authors: Joo Heesoo , Maskery Brian A. , Francois Watkins Louise K. , Park Joohyun , Angelo Kristina M. , Halsey Eric S. 
Published: July 2024

AbstractIn the United States, typhoid vaccination is recommended for international travelers to areas with a recognized risk of typhoid exposure. Using MarketScan® Commercial Database from 2016 through 2022, we estimated typhoid vaccination costs by route (injectable vs. oral) and provider setting (clinic vs. pharmacy). Of 165,930 vaccinated individuals, 99,471 received injectable and 66,459 received oral typhoid vaccines, with 88% and 17% respectively administered at clinics. Average costs for injectable vaccination were $132.91 per person [95% confidence interval (CI): $132.68–$133.13], with clinic and pharmacy costs at $136.38 [95% CI: $136.14–$136.63], and $107.45 [95% CI: $107.13–$107.77] respectively. Oral vaccination costs averaged $81.23 per person [95% CI: $81.14–$81.33], encompassing $86.61 [95% CI: $86.13– $87.10] at clinics and $80.14 [95% CI: $80.09–$80.19] at pharmacies. Out-of-pocket costs comprised 21% and 33% of total costs for injectable and oral vaccinations. These findings may inform clinical decision-making to protect international travelers’ health.
Biallelic variants inCOX18cause a mitochondrial disorder primarily manifesting as peripheral neuropathy
Authors: Armirola-Ricaurte Camila , Morant Laura , Adant Isabelle , Hamed Sherifa Ahmed , Pipis Menelaos , Efthymiou Stephanie , Amor-Barris Silvia , Atkinson Derek , Van de Vondel Liedewei , Tomic Aleksandra , de Vriendt Els , Zuchner Stephan , Ghesquiere Bart , Hanna Michael , Houlden Henry , Lunn Michael P , Reilly Mary M , Rasic Vedrana Milic , Jordanova Albena 
Published: July 2024

AbstractDefects in mitochondrial dynamics are a common cause of Charcot-Marie-Tooth disease (CMT), while primary deficiencies in the mitochondrial respiratory chain (MRC) are rare and atypical for this etiology. This study aims to reportCOX18as a novel CMT-causing gene. This gene encodes an assembly factor of mitochondrial Complex IV (CIV) that translocates the C-terminal tail of MTCO2 across the mitochondrial inner membrane.Exome sequencing was performed in four affected individuals. The patients and available family members underwent thorough neurological and electrophysiological assessment. The impact of one of the identified variants on splicing, protein levels, and mitochondrial bioenergetics was investigated in patient-derived lymphoblasts. The functionality of the mutant protein was assessed using a Proteinase K protection assay and immunoblotting. Neuronal relevance of COX18 was assessed in aDrosophila melanogasterknockdown model.Exome sequencing coupled with homozygosity mapping revealed a homozygous splice variant c.435-6A>G inCOX18in two siblings with early-onset progressive axonal sensory-motor peripheral neuropathy. By querying external databases, we identified two additional families with rare deleterious biallelic variants inCOX18. All affected individuals presented with axonal CMT and some patients also exhibited central nervous system symptoms, such as dystonia and spasticity. Functional characterization of the c.435-6A>G variant demonstrated that it leads to the expression of an alternative transcript that lacks exon 2, resulting in a stable but defective COX18 isoform. The mutant protein impairs CIV assembly and activity, leading to a reduction in mitochondrial membrane potential. Downregulation of theCOX18homolog inDrosophila melanogasterdisplayed signs of neurodegeneration, including locomotor deficit and progressive axonal degeneration of sensory neurons.Our study presents genetic and functional evidence that supportsCOX18as a newly identified gene candidate for autosomal recessive axonal CMT with or without central nervous system involvement. These findings emphasize the significance of peripheral neuropathy within the spectrum of primary mitochondrial disorders and the role of mitochondrial CIV in the development of CMT. Our research has important implications for the diagnostic workup of CMT patients.
Kidney transcriptomics signature of prospective rapid diabetic kidney disease progression
Authors: Acoba Dianne , Levin Anna , Witasp Anna , Ebefors Kerstin , Mölne Johan , Greasley Peter J. , Nyström Jenny , Wernerson Annika , Reznichenko Anna 
Published: July 2024

ABSTRACTPrevious cross-sectional transcriptomic studies on diabetic kidney disease (DKD) kidney tissue have shown correlations between gene expression and both disease status and kidney function at time of biopsy, but longitudinal data is scarce. We utilized clinical follow-up data up to five years post-biopsy, linking the transcriptomes of diagnostic kidney biopsies to progression rates and outcomes in 19 DKD patients. Patients were stratified into “rapid progressors” and “non-rapid progressors” based on clinical parameters (eGFR slope, CKD stage advancement, degree of albuminuria, composite of kidney failure or 40% eGFR decline). Differential expression and pathway enrichment analyses were performed to identify dysregulated genes and pathways associated with rapid progression. We identified 265 genes in glomeruli and tubulointerstitium that were significantly modulated in rapid vs non-rapid DKD progression. Rapid progression-associated genes showed enrichment for well-established (extracellular matrix organization, inflammation) as well as novel pathways in the context of DKD (circadian rhythm, cytoskeleton reorganization,NOTCHsignaling). This study illuminates kidney gene expression patterns that may be predictive of rapid progression in DKD and are distinct from those associated with cross-sectional kidney function.
Geospatial Analysis of Multilevel Socio-environmental Factors Impacting theCampylobacterBurden Among Infants in Rural Eastern Ethiopia: A One Health Perspective
Authors: Li Xiaolong , Chen Dehao , Liang Song , Hassen Jemal Yousuf , McKune Sarah L. , Havelaar Arie H. , Blackburn Jason K. 
Published: July 2024

AbstractIncreasing attention has focused on health outcomes ofCampylobacterinfections among children under five years in low-resource settings. Recent evidence suggests colonization ofCampylobacterspecies contributes to environmental enteric dysfunction, malnutrition, and growth faltering in young children.Campylobacterspecies are zoonotic, and factors from humans, animals, and the environment are involved in transmission. Few studies have assessed geospatial effects of environmental factors along with human and animal factors onCampylobacterinfections. Here, we leveragedCampylobacterGenomics and Environmental Enteric Dysfunction (CAGED) project data to model multiple socio-environmental factors onCampylobacterburden among infants in Eastern Ethiopia. Stool samples from 106 infants were collected monthly from birth through the first year of life (December 2020 – June 2022). Genus-specific Taqman real-time PCR was performed to detect and quantifyCampylobacterspp. and calculate cumulativeCampylobacterburden for each child as the outcome variable. Thirteen regional environmental covariates describing topography, climate, vegetation, soil, and human population density were combined with household demographics, livelihoods/wealth, livestock ownership, and child-animal interactions as explanatory variables. We dichotomized all continuous outcome and explanatory variables and built logistic regression models for the first and second half of the infant’s first year of life. Infants being female, living in households with cattle, reported to have physical contact with animals, or reported to have mouthed soil or animal feces had increased odds of higher cumulativeCampylobacterburden in Eastern Ethiopia. Future interventions should focus on infant-specific transmission pathways and create adequate separation of domestic animals from humans to prevent potential fecal exposures.
The ERK5 MAP kinase regulates annexin complexes and membrane dynamics in embryonic stem cells
Authors: Brown Helen A. , Guillet Ludivine , Williams Charles A. C. , Shaw Hayley , Zhou Houjiang , Rios-Szwed Diana , Fernandez-Alonso Rosalia , McMulkin Liam , Stavridis Marios P. , Findlay Greg M. 
Published: July 2024

SummaryThe ERK5 MAP kinase signalling pathway controls key processes in mouse Embryonic Stem Cells (mESCs) maintenance, including expression of naïve pluripotency genes and a transcriptional programme for stem cell rejuvenation. However, quantitative proteomics suggests that ERK5 signalling controls levels of proteins implicated in diverse biological processes. Here, we show that Annexin A2 (ANXA2) and its accessory protein S100A10, which are implicated in regulation of membrane dynamics, are major targets of the ERK5 signalling pathway in mESCs. ERK5 activation promotes expression of the ANXA2/S100A10 protein complex via transcriptional induction of the KLF2 pluripotency factor. Furthermore, either ERK5 signalling or ectopic expression of the ANXA2/S100A10 complex promotes formation of membrane protrusions in mESCs. Our data therefore identify a new function for the ERK5 pathway in regulation of an Annexin complex and membrane dynamics, which may have implications for development and disease.