bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do fungi look like macroparasites? Quantifying the patterns and mechanisms of aggregation for host-fungal parasite relationships
Authors: Schrock Sarah A.R. , Walsman Jason C. , DeMarchi Joseph , LeSage Emily H. , Ohmer Michel E.B. , Rollins-Smith Louise A. , Briggs Cheryl J. , Richards-Zawacki Corinne L. , Woodhams Douglas C. , Knapp Roland A. , Smith Thomas C. , Haddad Célio F.B. , Guilherme Becker C. , Johnson Pieter T.J. , Wilber Mark Q. 
Published: August 2024

AbstractMost hosts contain few parasites, whereas few hosts contain many. This pattern, known as aggregation, is well-documented in macroparasites where parasite intensity distribution among hosts affects host-parasite dynamics. Infection intensity also drives fungal disease dynamics, but we lack a basic understanding of host-fungal aggregation patterns, how they compare to macroparasites, and if they reflect biological processes. To address these gaps, we characterized aggregation of the fungal pathogenBatrachochytrium dendrobatidis(Bd) in amphibian hosts. Utilizing the slope of Taylor’s Power Law, we found Bd intensity distributions were more aggregated than macroparasites, conforming closely to lognormal distributions. We observed that Bd aggregation patterns are strongly correlated with known biological processes operating in amphibian populations, such as epizoological phase—invasion, post-invasion, and enzootic—and intensity-dependent disease mortality. Using intensity-dependent mathematical models, we found evidence of evolution of host resistance based on aggregation shifts in systems persisting with Bd following disease-induced declines. Our results show that Bd aggregation is highly conserved across disparate systems and is distinct from aggregation patterns in macroparasites, and contains signatures of potential biological processes of amphibian-Bd systems. Our work lays a foundation to unite host-fungal dynamics under a common theoretical framework and inform future modeling approaches that may elucidate host-fungus interactions.
The Balanced Mind and its Intrinsic Neural Timescales in Advanced Meditators
Authors: Malipeddi Saketh , Sasidharan Arun , Venugopal Rahul , Ventura Bianca , Bauer Clemens Christian , P.N. Ravindra , Mehrotra Seema , John John P , Kutty Bindu M , Northoff Georg 
Published: August 2024

AbstractA balanced mind, or equanimity, cultivated through meditation and other spiritual practices, is considered one of the highest mental states. Its core features include deidentification and non-duality. Despite its significance, its neural correlates remain unknown. To address this, we acquired 128-channel EEG data (n = 103) from advanced and novice meditators (from the Isha Yoga tradition) and controls during an internal attention (breath-watching) and an external attention task (visual-oddball paradigm). We calculated the auto-correlation window (ACW), a measure of brain’s intrinsic neural timescales (INTs) and assessed equanimity through self-report questionnaires. Advanced meditators showed higher levels of equanimity and shorter duration of INTs (shorter ACW) during breath-watching, indicating deidentification with mental contents. Furthermore, they demonstrated no significant differences in INTs between tasks, indicating non-dual awareness. Finally, shorter duration of INTs correlated with the participants’ subjective perceptions of equanimity. In conclusion, we show that the shorter duration of brain’s INT may serve as a neural marker of equanimity.
Transport of herbicides by PIN-FORMED auxin transporters
Authors: Schulz Lukas , Ung Kien Lam , Koutnik-Abele Sarah , Stokes David L , Pedersen Bjørn Panyella , Hammes Ulrich Z. 
Published: August 2024

SUMMARYAuxins are a group of phytohormones that control plant growth and development1. Their crucial role in plant physiology has inspired development of potent synthetic auxins that can be used as herbicides2. Phenoxyacetic acid derivatives are a widely used group of auxin herbicides in agriculture and research. Despite their prevalence, the identity of the transporters required for distribution of these herbicides in plants is both poorly understood and the subject of controversial debate3,4. Here we show that PIN-FORMED auxin transporters transport a range of phenoxyacetic acid herbicides across the membrane and we characterize the molecular determinants of this process using a variety of different substrates as well as protein mutagenesis to control substrate specificity. Finally, we present Cryo-EM structures ofArabidopsis thalianaPIN8 with 2,4-dichlorophenoxyacetic acid (2,4-D) or 4-chlorophenoxyacetic acid (4-CPA) bound. These structures represent five key states from the transport cycle, allowing us to describe conformational changes associated with substrate binding and transport across the membrane. Overall, our results reveal that phenoxyacetic acid herbicides use the same export machinery as endogenous auxins and exemplify how transporter binding sites undergo transformations that dictate substrate specificity. These results enable development of novel synthetic auxins and for guiding precision breeding of herbicide resistant crop plants.
Genome-wide A→G and C→T Mutations Induced by Functional TadA Variants inEscherichia coli
Authors: Wang Hao , Dong Zhengxin , Shi Jingyi , Chen Lei , Sun Tao , Zhang Weiwen 
Published: August 2024

AbstractThe fusion expression of DNA replication-related proteins with nucleotide deaminase enzymes promotes random mutations in bacterial genomes, thereby increasing genetic diversity among population. Most previous studies have focused on cytosine deaminase, which produces only C→T mutations, significantly limiting the variety of mutation types. In this study, we developed a fusion expression system by combining DnaG (RNA primase) with adenine deaminase TadA-8e (DnaG-TadA) inEscherichia coli, which is capable of rapidly introducing A→G mutations into theE. coligenome, resulting in a 664-fold increase in terms of mutation rate. Additionally, we engineered a dual-functional TadA variant, TadAD, and then fused it with DnaG. This construct introduced both C→T and A→G mutations into theE. coligenome, with the mutation rate further increased by 370-fold upon co-expression with an uracil glycosylase inhibitor (DnaG-TadAD-UGI). We applied DnaG-TadA and DnaG-TadAD-UGI systems to the adaptive laboratory evolution for Cd2+and kanamycin resistance, achieving an 8.0 mM Cd2+and 200 μg/mL kanamycin tolerance within just 17 days and 132 hours, respectively. Compared to conventional evolution methods, the final tolerance levels were increased by 320% and 266%, respectively. Our work offers a novel strategy for random mutagenesis inE. coliand potentially other prokaryotic species.Abstract FigureFor TOC only
HEAD AND SHOULDERS - THE IMPACT OF AN EXTENDED HEAD MODEL ON THE SIMULATION AND OPTIMIZATION OF TRANSCRANIAL ELECTRIC STIMULATION
Authors: Van Hoornweder Sybren , Cappozzo Vittoria , De Herde Laura , Puonti Oula , Siebner Hartwig R. , Meesen Raf L.J. , Thielscher Axel 
Published: August 2024

AbstractElectric field calculations are increasingly used for dose characterization of transcranial electrical stimulation (tES), but existing open-source head models are inaccurate for extracephalic montages that include electrodes placed on the neck or shoulder. We introduce the “Ernie Extended” model, an MRI- and CT-derived open-source head model extending to the upper shoulder region. Simulations of extracephalic tES targeting the cerebellum and supplementary motor area show significant differences in electric fields when using Ernie Extended compared to the non-extended Ernie model. Additionally, we propose an electrode layout that complements the electroencephalography 10– 20 system with extracephalic electrode positions. We demonstrate the use of this layout for optimizing multi-electrode tES montages for cerebellar stimulation, enhancing focality and reducing off-target stimulation, particularly of the spinal cord. Our results highlight the practical value of the Ernie Extended model for accurately characterizing doses produced by extracephalic tES montages and when targeting more caudal brain regions.
A Systematic Analysis of Read-Across Adaptations in Testing Proposal Evaluations by the European Chemicals Agency
Authors: Roe Hannah M. , Tsai Han-Hsuan D. , Ball Nicholas , Wright Fred A. , Chiu Weihsueh A. , Rusyn Ivan 
Published: August 2024

AbstractAn important element of the European Union’s “Registration, Evaluation, Authorisation and Restriction of Chemicals” (REACH) regulation is the evaluation by the European Chemicals Agency (ECHA) of testing proposals submitted by the registrants to address data gaps in standard REACH information requirements. The registrants may propose adaptations, and ECHA evaluates the reasoning and issues a written decision. Read-across is a common adaptation type, yet it is widely assumed that ECHA often does not agree that the justifications are adequate to waive standard testing requirements. From 2008 to August 2023, a total of 2,630 Testing Proposals were submitted to ECHA; of these, 1,538 had published decisions that were systematically evaluated in this study. Each document was manually reviewed, and information extracted for further analyses. Read-across hypotheses were standardized into 17 assessment elements (AEs); each submission was classified as to the AEs relied upon by the registrants and by ECHA. Data was analyzed for patterns and associations. Testing Proposal Evaluations (TPEs) with adaptations comprised 23% (353) of the total; analogue (168) or group (136) read-across adaptations were most common. Of 304 read-across-containing TPEs, 49% were accepted; the odds of acceptance were significantly greater for group read-across submissions. The data was analyzed by Annex (i.e., tonnage), test guideline study, read-across hypothesis AEs, as well as target and source substance types and their structural similarity. While most ECHA decisions with both positive and negative decisions on whether the proposed read-across was adequate were context-specific, a number of significant associations were identified that influence the odds of acceptance. Overall, this analysis provides an unbiased overview of 15 years of experience with testing proposal-specific read-across adaptations by both registrants and ECHA. These data will inform future submissions as they identify most critical AEs to increase the odds of read-across acceptance.
Extensive transmission and variation in a functional receptor for praziquantel resistance in endemicSchistosoma mansoni
Authors: Berger Duncan J. , Park Sang-Kyu , Crellen Thomas , Vianney Tushabe John , Kabatereine Narcis B. , Cotton James A. , Sanya Richard , Elliot Alison , Tukahebwa Edridah M. , Adriko Moses , Standley Claire J. , Gouvras Anouk , Kinung’hi Safari , Haas Helmut , Rabone Muriel , Emery Aidan , Lamberton Poppy H. L. , Webster Bonnie L. , Allan Fiona , Buddenborg Sarah , Berriman Matthew , Marchant Jonathan S. , Doyle Stephen R. , Webster Joanne P. 
Published: August 2024

AbstractMass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570Schistosoma mansonisamples (and the closely related outgroup species,S. rodhaini)from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQvariants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles.One Sentence SummaryPopulation genomics and functional genetics of praziquantel resistance inSchistosoma mansoni
Multiyear Improvement In Batting Skills Following Targeted Perceptual Cognitive Training In Softball
Authors: Muraskin Jordan , Sherwin Jason 
Published: August 2024

AbstractBackgroundMaking quick, accurate decisions is crucial in competitive sports like softball, where perceptual-cognitive skills can significantly impact on-field performance. This study evaluates the long-term effectiveness of a targeted perceptual-cognitive training program, delivered through the uHIT platform, on improving batting performance in collegiate softball players.MethodsA longitudinal analysis was conducted on data collected from both NCAA and NAIA softball teams over multiple seasons. The study used Bayesian statistical methods to assess the impact of cognitive training on on-base plus slugging percentage (OPS). The analysis incorporated weighted models to account for variability in games played and differences between teams, and the influence of team and year-division effects was considered. Key metrics, including Decision AUC and Response Time, were tracked to evaluate perceptual-cognitive improvements.ResultsThe results demonstrated significant improvements in OPS for teams that participated in the cognitive training intervention, with the weighted models indicating a substantial effect of the training on performance. Notably, the intervention was most effective in teams with higher training intensity, as evidenced by the permutation test results. The Bayesian analysis also revealed that the intervention led to statistically significant improvements in decision-making and response times, translating into enhanced on-field performance.ConclusionThe findings support the effectiveness of perceptual-cognitive training in improving real-world athletic performance in softball. The uHIT platform, as an ecologically valid training tool, has demonstrated its potential to serve as a critical component of athletic development programs. Future research should explore the long-term retention of these cognitive gains and their application across different sports and competitive levels.
Muscle Type-Specific Modulation of Autophagy Signaling in Obesity: Effects of Caloric Restriction and Exercise
Authors: Ji Fujue , Kim Jong-Hee 
Published: August 2024

BackgroundObesity causes metabolic dysregulation and contributes to various diseases, with autophagy playing a pivotal role in this process. Autophagy, a cellular recycling mechanism, is influenced by factors beyond obesity, like caloric restriction (CR) and CR combined with exercise (CR+Ex), which modulate autophagy in obesity management. However, the regulation of autophagy in skeletal muscle under conditions of obesity, CR, and CR+Ex remains poorly understood.MethodMice were divided into six groups: normal diet, normal diet CR, normal diet CR+Ex, high-fat diet, high-fat diet CR, and high-fat diet CR+Ex. All mice were fed ad libitum with either a normal or high-fat diet for the first four months, followed by the respective interventions for the subsequent four months. Body composition, motor function, and skeletal muscle autophagy signaling were assessed.ResultsObesity resulted in increased total mass, lean mass, fat mass, and fat percentage in tissue; decreased grip strength and endurance capacity. Notably, CR+Ex reduced total mass, lean mass, and fat mass in obese mice. In both normal and obese conditions, the expression of autophagy markers p62, LC3B-I, and LC3B-II is significantly higher in red muscle. Obesity leads to a reduction in cathepsin L expression, while CR further increased LC3B-I expression in red muscle.ConclusionCR+Ex proves to be an effective strategy for counteracting the adverse changes in body composition associated with obesity. Unlike red muscle, white muscle exhibits lower baseline autophagic levels and may necessitate elevated expression of autophagy-related proteins, such as cathepsin L, to mitigate the negative effects of obesity.
Multi-omics analysis of virus-permissive versus hostile cellular states reveals protein networks controlling virus infection
Authors: Chen Honglin , Charles Philip D , Gu Quan , Liberatori Sabrina , Robertson David L , Palmarini Massimo , Wilson Sam J , Mohammed Shabaz , Castello Alfredo 
Published: August 2024

SUMMARYThe capacity of host cells to sustain or restrict virus infection is influenced by their proteome. Understanding the compendium of proteins defining cellular permissiveness is key to many questions in fundamental virology. Here, we apply a multiomic approach to determine the proteins that are associated with highly permissive, intermediate, and hostile cellular states. We observed two groups of differentially regulated genes: i) with robust changes in mRNA and protein levels, and ii) with protein/RNA discordances. Many of the latter are classified as interferon stimulated genes (ISGs) but have no reported antiviral activity. This suggests that IFN-dependent changes in mRNA levels do not imply antiviral function. Phosphoproteomics revealed an additional regulatory layer involving non-signalling proteins with altered phosphorylation. Indeed, we confirmed that several permissiveness-associated proteins with changes in abundance or phosphorylation regulate infection fitness. Altogether, our study provides a comprehensive and systematic map of the cellular alterations driving virus susceptibility.
The Impact of Brain-Derived Neurotrophic Factor rs6265 (Val66Met) Polymorphism on Therapeutic Electrical Stimulation for Peripheral Nerve Regeneration: A Preclinical Study of Therapy-Genotype Interactions
Authors: Walters Jordan , Quezada Maria J. , He Suning , Steece-Collier Kathy , Collier Timothy J. , Sortwell Caryl E. , Franz Colin K. 
Published: August 2024

AbstractThe Impact of Brain-Derived Neurotrophic Factor rs6265 (Val66Met) Polymorphism on Therapeutic Electrical Stimulation for Peripheral Nerve Regeneration: A Preclinical Study of Therapy-Genotype InteractionsIntroductionPeripheral nerve injuries (PNIs) significantly impact patient quality of life. Therapeutic electrical stimulation (TES) shows promise in enhancing nerve regeneration, but outcomes vary widely. This study investigates the impact of the rs6265 single nucleotide polymorphism (SNP) on TES efficacy in a preclinical rat model and human stem cell-derived motor neurons.MethodsWild-type (WT) and rs6265 variant rats underwent sciatic nerve transection and received either TES or sham treatment. Muscle reinnervation was assessed through compound muscle action potentials and muscle fiber cross-sectional area. Isogenic human iPSC-derived motor neurons were used to study activity-dependent BDNF secretion.ResultsTES improved muscle reinnervation and fiber size in WT but not rs6265 allele carriers. rs6265 allele carriers exhibited impaired activity-dependent BDNF secretion in vitro.DiscussionThe rs6265 polymorphism influences TES efficacy, highlighting the need for personalized approaches in PNI treatment. These findings suggest that genetic screening could optimize therapeutic outcomes.Clinical RelevanceUnderstanding genetic factors affecting TES response can enhance treatment strategies for PNI, potentially improving patient recovery and reducing outcome variability.
qBiCo: A method to assess global DNA conversion performance in epigenetics via single-copy genes and repetitive elements
Authors: Karkala Faidra , Simons Roy B. , Claessens Floor , Kalamara Vivian , Kayser Manfred , Vidaki Athina 
Published: August 2024

AbstractHuman DNA methylation profiling offers great promises in various biomedical applications, including ageing, cancer and even forensics. So far, most DNA methylation techniques are based on a chemical process called sodium bisulfite conversion, which specifically converts non-methylated cytosines into uracils. However, despite the popularity of this approach, it is known to cause DNA fragmentation and loss affecting standardization, while incomplete conversion may result in potential misinterpretation of methylation-based outcomes. To offer the community a solution, we developed qBiCo - a novel quality-control method to address the quantity and quality of bisulfite-converted DNA. qBiCo is a 5-plex, TaqMan®probe-based, quantitative (q)PCR assay that amplifies single- and multi-copy DNA fragments of converted and non-converted nature. It estimates four parameters: converted DNA concentration, fragmentation, global conversion efficiency, and potential PCR inhibition. We optimized qBiCo using synthetic DNA standards and assessed it using standard developmental validation criteria, showcasing that qBiCo is reliable, robust and sensitive down to picogram level. We also evaluated its performance by testing decreasing DNA amounts using several commercial bisulfite conversion kits. Depending on the starting DNA quantity, bisulfite-converted DNA recoveries ranged from 8.5 – 100 %, conversion efficiencies from 78 - 99.9 %, while certain kits highly fragment DNA, demonstrating large variability in their performance. Towards building a prototype tool, we further optimized key functionalities, for example, by replacing the poorest performing single-plex assay and creating a more representative DNA standard. Aiming to scale-up and move towards implementation, we successfully transferred and validated our novel method in six different qPCR platforms from different major manufacturers. Overall, with the present study, we offer researchers in the epigenetic field a novel long-awaited QC tool that for the first time allows them to measure key quality and quantity parameters of the most popular DNA conversion process. The tool also enables standardization to prevent inconsistent data and false outcomes in the future, regardless of the downstream experimental analysis of DNA methylation-based research and applications across different fields of biology and biomedicine.