bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational Chlorpyrifos Exposure Imparts Lasting Alterations to the Rat Somatosensory Cortex
Authors: Koenig Jeffrey A. , Haga Catherine , Cramer Nathan , Keller Asaf 
Published: February 2025

ABSTRACTChlorpyrifos is an organophosphorus pesticide used extensively in agricultural and residential settings for nearly 60 years. Gestational, sub-acute exposure to chlorpyrifos is linked to increased prevalence of neurodevelopmental disorders. Animal studies have modeled these neurobehavioral detriments, however, the functional alterations in the brain induced by this exposure remain largely unknown. To address this, we used a rat model of gestational chlorpyrifos exposure to interrogate the alterations in the developing somatosensory (barrel) cortex. Rat dams were exposed to chlorpyrifos (5 mg/kg) or vehicle on gestational days 18-21 via subcutaneous injection, with no overt acute toxicity. Acetylcholinesterase was modestly inhibited but returned to baseline levels by postnatal day 12. We performed whole-cell patch clamp recordings on postnatal days 12-20 in both male and female progeny of the treated dams. A spike timing dependent plasticity protocol revealed changes to the normal development of use-dependent plasticity, including interference in long-term synaptic depression. Recording inhibitory synaptic activity revealed an increase in the frequency of spontaneous postsynaptic currents and in paired pulse ratios, in conjunction with a significant decrease in miniature postsynaptic currents. These findings suggest a presynaptic mechanism of inhibited GABA release, with potential disinhibition of inhibitory neurons. Evaluation of barrel cortex development displayed disruptions to normal barrel field patterning, with increases in both the septal area and total barrel field. We provide evidence for functional and structural alterations during brain development induced byin uteroexposure to the organophosphorus pesticide chlorpyrifos that may account for the well-established behavioral outcomes.SIGNIFICANCE STATEMENTWe demonstrate persistent alterations to synaptic function and plasticity in the somatosensory cortex following a brief, sub-acute exposure to the organophosphorus pesticide chlorpyrifos in a gestational rat model. These occur in conjunction with structural changes to cellular patterning of this brain region. These previously unknown consequences are potential causal mechanisms to the well-established neurodevelopmental detriments associated with early life exposure to chlorpyrifos. Clarifying these mechanisms could aid in ameliorating or preventing their persistent effects.
Local variations in L/M ratio influence the detection and color naming of small spots
Authors: Greene Maxwell J. , Pandiyan Vimal P. , Sabesan Ramkumar , Tuten William S. 
Published: February 2025

AbstractThe distribution of long-wavelength sensitive (L) and middle-wavelength sensitive (M) cones in the retina determines how different frequencies of incident light are sampled across space, and has been hypothesized to influence spatial and color vision. We asked whether the detection and color naming of small, short-duration increment stimuli depend on the relative numbers of L and M cones illuminated. Stimuli were corrected for optical aberrations by an adaptive optics system, and targeted to locations in the parafovea where cone spectral types were known. We found that sensitivity to 680 nm light, normalized by sensitivity to 543 nm light, grew with the proportion of L cones at the stimulated locus, though intra- and intersubject variability was considerable. A similar trend was derived from a simple model of the achromatic (L+M) pathway, as well as from photoreceptor-level ideal observers, suggesting that small spot detection mainly relies on a non-opponent mechanism. Most stimuli were called achromatic, with red and green responses becoming more common as stimulus intensity and local L/M ratio symmetry increased. Our detection data confirm earlier reports that small spot psychophysics can reveal information about local cone topography, and our color naming findings suggest that chromatic sensitivity may improve when the L/M ratio approaches unity.
Sparse testcrossing for early-stage genomic prediction of general combining ability to increase genetic gain in maize hybrid breeding programs
Authors: González-Diéguez David O. , Atlin Gary N. , Beyene Yoseph , Wegary Dagne , Gemenet Dorcus C. , Werner Christian R. 
Published: February 2025

1ABSTRACTSparse testcrossing is an effective strategy for increasing both short- and long-term genetic gain in hybrid breeding programs. Maize hybrid breeding programs aim to develop new hybrid varieties by crossing genetically distinct parents from different heterotic pools, exploiting heterosis for improved performance. The programs typically consist of two main components: population improvement and product development. The population improvement component aims to enhance the heterotic pools through reciprocal recurrent selection based on general combining ability (GCA). However, especially in the early stages of testing, evaluating large numbers of hybrid combinations to estimate GCA is impractical due to considerable logistical challenges and costs. Therefore, breeders often evaluate the initial population of selection candidates using only a single tester to narrow down the candidate pool before further evaluation. Using a single tester, however, may not adequately represent the heterotic pool, leading to inaccurate GCA estimates and suboptimal selection decisions. To address this, we propose sparse testcrossing for early-stage testing, where subsets of candidate genotypes are testcrossed with different testers, connected through a genomic relationship matrix. We conducted stochastic simulations to compare various sparse testcrossing designs with a conventional testcross strategy using a single tester over 15 cycles of reciprocal recurrent genomic selection. Our results show that using 3-5 testers, sparsely distributed among full-sibs, sparse testcrossing offers breeders a practical balance between simple testcross designs, resource efficiency, and increased prediction accuracy for GCA, ultimately resulting in increased rates of genetic gain.Key messageSparse testcrossing with 3-5 testers enhances genetic gain in hybrid breeding programs, offering a practical balance of simple testcross designs, resource efficiency, and increased prediction accuracy for general combining ability.
Efficient Prospective Electric Field-Informed Localization of Motor Cortical Targets of Transcranial Magnetic Stimulation
Authors: Schultheiss David Luis , Turi Zsolt , Marmavula Srilekha , Reinacher Peter Christoph , Demerath Theo , Straehle Jakob , Boedecker Joschka , Mittner Matthias , Vlachos Andreas 
Published: February 2025

AbstractTranscranial magnetic stimulation (TMS) is a versatile non-invasive tool for brain mapping and neu-romodulation in both healthy individuals and patients. Effective TMS-based causal brain mapping relies on precise localization of cortical targets. Current state-of-the-art approaches use statistical methods to quantify the relationship between TMS-induced electric fields (E-fields) and motor evoked potential (MEP) amplitudes. However, this method typically relies on the random selection of coil configurations, which limits its efficacy. In this study, we present a novel optimization strategy for TMS-based motor mapping by prospectively selecting coil configurations based on their E-field characteristics using an iterative sampling algorithm called farthest point sampling (FPS). Through a combination of theoretical analysis, simulation and experimental validation including 10 healthy individuals, we systematically evaluated the performance of FPS against the random sampling approach. Our results demonstrate that FPS is twice as efficient as random sampling in reducing the number of trials required for estimating the motor map, while also being more robust across participants and less susceptible to noise. These findings highlight the potential of FPS to significantly enhance the efficiency of motor mapping, paving the way for the development of more effective TMS mapping algorithms.
Hypoxia-activated fluorescent probes as markers of oxygen levels in plant cells and tissues
Authors: Perri Monica , Khan M. Shahneawz , Wallabregue Antoine L. D. , Voloboeva Viktoriia , Ridgway Amber M. , Smith Edward N. , Bolland Hannah , Hammond Ester M. , Conway Stuart J. , Weits Daan A. , Flashman Emily 
Published: February 2025

SummaryLow oxygen signalling in plants is important in development and stress responses. Measurement of oxygen levels in plant cells and tissues is hampered by a lack of chemical tools with which to reliably detect and quantify endogenous oxygen availability. We have exploited hypoxia-activated fluorescent probes to visualise low oxygen (hypoxia) in plant cells and tissues.We applied 4-nitrobenzyl (4NB-) resorufin and methyl-indolequinone (MeIQ-) resorufin toArabidopsis thalianawhole cells and seedlings exposed to hypoxia (1% O2) and normoxia (21% O2). Confocal microscopy and fluorescence intensity measurements were used to visualise regions of resorufin fluorescence.Both probes enterA.thalianawhole cells and are activated to fluoresce selectively in hypoxic conditions. Similarly, incubation withA.thalianaseedlings resulted in hypoxia-dependent activation of both probes and observation of fluorescence in hypoxic roots and leaf tissue. MeIQ-Resorufin was used to visualise endogenous hypoxia in lateral root primordia of normoxicA.thalianaseedlings.Oxygen measurement in plants until now has relied on invasive probes or genetic manipulation. Use of these chemical probes to detect applied and endogenous hypoxia has the potential to facilitate a greater understanding of oxygen dynamics in plant cells and tissues, allowing correlation of oxygen concentrations with adaptive and developmental responses to hypoxia.
Mutant IDH impairs chromatin binding by PDGFB to promote chromosome instability
Authors: Curry Rachel N. , McDonald Malcolm F. , He Peihao , Lozzi Brittney , Ko Yeunjung , O’Reilly Isabella , Rosenbaum Anna , Kwon Wookbong , Fahim Leyla , Marcus Joshua , Powell Noah , Wang Su , Ma Jin , Multani Asha , Choi Dong-Joo , Sardar Debo , Mohila Carrie , Lee Jason , Gallo Marco , Harmanci Arif , Harmanci Akdes Serin , Deneen Benjamin , Rao Ganesh 
Published: February 2025

AbstractNon-canonical roles for growth factors in the nucleus have been previously described, but their mechanism of action and biological roles remain enigmatic. Platelet-derived growth factor B (PDGFB) can drive formation of low-grade glioma and here we show that it localizes to the nucleus of human glioma cells where it binds chromatin to preserve genome stability and cell lineage. Failure of PDGFB to localize to the nucleus leads to chromosomal abnormalities, aberrant heterochromatin architecture and accelerated tumorigenesis. Furthermore, nuclear localization of PDGFB is reliant upon the expression levels and mutation status of isocitrate dehydrogenase (IDH). Unexpectedly, we identified macrophages as the predominant source of PDGFB in human, finding that immune-derived PDGFB can localize to the nucleus of glioma cells. Collectively, these studies show that immune derived PDGFB enters the nucleus of glioma cells to maintain genomic stability, while identifying a new mechanism by which IDH mutations promote gliomagenesis.
Heightened non-testing risk mitigation blood donor screening with retrospective transcription-mediated amplification testing during a 2023 local Florida malaria cluster
Authors: Sullivan David J. , Lanteri Marion , Bres Vanessa , Hanhan Measa , Pagan Marlene , Rey Alejandro , Thomas Korena , Sasnett Betsy , Reik Rita A. 
Published: February 2025

AbstractBackgroundTransfusion-transmitted malaria risk in the USA is estimated at less than one per ten million blood donations or about 1 case every 2 years. A total of 18 autochthonous malaria infections have been reported in the USA since 2003: eight cases in 2003 and ten cases in 2023 with fifteen reported from Florida. From May to July 2023 in Sarasota County, Florida, symptomaticP. vivaxmalaria was detected in seven individuals with no recent malaria travel history.Study Design and MethodsIn the absence of an FDA-approved blood donor screening test for malaria at the time, the local blood center responded to this 2023 cluster by implementing a non-testing risk mitigation strategy of escalating blood donor screening measures and pathogen reduction. Potential blood supply safety enhancement by use of additional nucleic acid testing (NAT) on samples from donors in impacted areas was studied retrospectively using the Procleix Plasmodium Assay, a transcription-mediated amplification detecting five humanPlasmodiumspecies 18S ribosomal RNA with a limit of detection ranging from 2-7 infected erythrocytes per mL.ResultsAmong the 435 valid study samples from accepted healthy blood donors, screened with heightened non-testing measures in the 4-6 mile radius of malaria-impacted area, all samples were nucleic acid test non-reactive.DiscussionThe blood center strategy in response to the local 2023 malaria outbreak maintained the blood supply safety with no transfusion-transmitted malaria and no retrospective evidence ofPlasmodiumin the 435 valid samples collected from blood donors residing in impacted areas.
T Cell Dysfunction in Cutaneous Leishmaniasis at Single-Cell Resolution
Authors: Avila Jonathan Peña , Singh Youvika , de Souza Fernanda Mesquita , de Assunção Stella Francy , Damasceno Samara , Guedes Herbert Leonel de Matos , Cunha Thiago M. , Filho Roberto Bueno , da Silva João Santana , Nakaya Helder I. 
Published: February 2025

SummaryBackgroundCutaneous leishmaniasis (CL) is characterized by immune dysregulation that facilitates chronic infection.ObjectiveTo investigate the role of T cells in the immunopathology of CL by characterizing the immune landscape of skin lesions using single-cell RNA sequencing (scRNA-seq).MethodsWe performed scRNA-seq to profile T cells from PBMC and skin lesions of CL patients.ResultsWe analyzed the transcriptional profile of distinct populations of CD4+ and CD8+ migratory T cells in CL lesions. CD8+ resident T cells displayed expression of exhaustion markers and were categorized into progenitor, transitional, and terminal stages, with HAVCR2 (TIM-3) identified as a potential driver of dysfunction. Compared to psoriasis and healthy skin, CL lesions showed a reduced frequency of regulatory T cells (Tregs), potentially linked to oxidative stress, DNA damage, and increased apoptosis. We also detected double-negative (DN) γδ T cells, suggesting their potential role in antigen presentation via MHC class II through TGF-β signaling.ConclusionThis study provides novel insights into immune evasion mechanisms in CL, identifying TIM-3, Treg modulation, and the functional role of DN γδ T cells as distinct potential targets for future immunotherapies.
Association Between Abnormal Sleep and Mortality Risk: A Nationwide Prospective Cohort Study of All-Cause and Cardiovascular disease Mortality
Authors: Ke Li , Li Ying , Zhao Lei , Xing Wenli , Jiang Sili 
Published: February 2025

AbstractBackgroundThe American Heart Association’s Life’s Essential 8 construct of ideal cardiovascular health now includes sleep duration, emphasizing the need to understand the implications of suboptimal sleep patterns. Recent studies have demonstrated that Life’s Essential 8 is correlated with the risk of all-cause mortality and CVD-specific mortality. However, although sleep duration being one of the components of Life’s Essential 8, the relationship between an individual’s sleep patterns and the risk of all-cause and CVD- specific mortality remains unclear.MethodsThe 2005–2018 National Health and Nutrition Examination Survey (NHANES) included 38,006 adults aged ≥20 years. The definitions of normal sleep duration (7–8 hours per night), short sleep duration (< 7 hours), and long sleep duration (> 8 hours) were based on the current literature. To evaluate the association between abnormal sleep patterns and both all-cause mortality and CVD mortality, a multinomial Cox regression analysis was conducted, adjusting for demographic and clinical factors.ResultsThe study utilized three models (Model I–III), first unadjusted and then adjusted for sociodemographic, lifestyle, and chronic disease factors. In the fully adjusted model, both short sleep (OR=1.25, 95% CI: 1.12–1.39, P<0.001) and long sleep (OR=1.30, 95% CI: 1.18–1.44, P<0.001) were found to be associated with an increased risk of all-cause mortality. Regarding CVD mortality, after full adjustment (Model III), only long sleep remained statistically significant (OR=1.28, 95% CI: 1.07–1.52, P=0.006), while the association for short sleep was no longer significant (OR=1.16, 95% CI: 0.94–1.43, P=0.176).ConclusionsAbnormal sleep duration (both short and long) was independently associated with an increased risk of all-cause mortality. Long sleep duration was associated with an increased risk of CVD mortality.
Mapping plant-scale variation in crop physiological traits and water fluxes
Authors: Caine Robert S. , Berry Peter M. , Storer Kate E. , Croft Holly L. 
Published: February 2025

AbstractNitrogen (N) is a vital plant element, affecting plant physiological processes, carbon and water fluxes and ultimately crop yields. However, N uptake by crops can vary over fine spatiotemporal scales, and optimising the application of N-fertiliser to maximise crop performance is challenging. To investigate the potential of spatially mapping the impact of N fertiliser application on crop physiological performance and yield, we leverage both optical and thermal data sampled from drone platforms and ground-level leaf measurements, across a range of different N, Sulphur (S) and sucrose treatments in winter wheat. Using leaf level hyperspectral reflectance data, leaf chlorophyll content was accurately modelled across fertiliser treatments via partial least squares regression (PLSR;R2= 0.93,P< 0.001). Leaf photosynthetic capacity (Vcmax) exhibited a strong linear relationship with leaf chlorophyll (R2= 0.77;P< 0.001). Using drone-acquired MERIS terrestrial chlorophyll index (MTCI) values as a proxy for leaf chlorophyll (R2= 0.76;P< 0.001),Vcmaxwas spatially mapped at the centimetre-scale. Thermal drone and ground measurements demonstrated that N application leads to cooler leaf temperatures, which led to a strong relationship with ground-measured leaf stomatal conductance (R2= 0.6;P< 0.01). Final grain yield was most accurately predicted by optical reflectance (MTCI,R2= 0.94;P< 0.001). Precise retrieval of leaf-level crop performance indicators from drones establishes significant potential for optimising fertiliser application, to reduce environmental costs and improve yields.
Multiple Neural Modules Orchestrate Conflict Processing
Authors: Sabo Melinda , Varlet Manuel , Grootswagers Tijl 
Published: February 2025

AbstractCognitive conflict is a ubiquitous aspect of our daily life, yet its underlying neural mechanisms remain debated. Competing theories propose that conflict processing is governed by either a domain-general system, multiple conflict-specific modules, or both types of systems, as evidenced by hybrid accounts. The aim of the current study was to settle this debate. We analyzed electroencephalogram (EEG) data from 507 participants (ages 20–70) who completed three conflict tasks: a change detection, a Simon, and a Stroop task. A novel decoding approach was adopted to distinguish between conflict and non-conflict trials. While within-task decoding showed robust effects, decoding across tasks yielded chance-level evidence. These findings support the idea that conflict processing relies on multiple conflict specific modules tailored to task-specific demands. By leveraging a large, diverse sample and a data-driven analysis, this study provides compelling evidence for conflict-specific neural mechanisms, offering new insights into the nature of conflict resolution and cognitive control.
Modeling Pyramidal Neurons Using Bidomain BEM and Hierarchical Matrix Approximation
Authors: Hasan Nahian I. , Sabino Vanine , Gomez Luis J. 
Published: February 2025

AbstractElectromagnetic brain stimulation uses electrodes or coils to induce electric fields (E-fields) in the brain and affect its activity. Our understanding of the precise effects of the device-induced E-fields on neural activity is limited. In this work, we present a novel boundary integral equation that enables the modeling of fully coupled E-fields from both neurons and stimulation devices. This boundary element approach is accelerated using fast direct solvers to allow for the analysis of realistic scenarios. We present examples, indicating the ability of our solver to analyze rat L2/3 pyramidal neurons derived from the blue brain project.
Pharmacokinetics of anti-SARS-CoV-2 monoclonal antibody SA55 injection in healthy participants
Authors: Zhou Yibo , Meng Xing , Li Jianhua , Wang Jin , Zeng Gang , Cao Yunlong , Hu Chaoying , Jin Ronghua 
Published: February 2025

AbstractTo explore novel treatment/prevention of COVID-19, a novel broad-spectrum neutralizing antibody injection, anti-SARS-CoV-2 antibody SA55 Injection (SA55 injection) was developed. Pharmacokinetics (PK) characteristics of SA55 injection were evaluated in a randomized, controlled, double-blind phase □ trial based on healthy participants aged 18-65 years. PK parameters (AUC0-∞, AUC0-t, and Cmax) were assessed using one-way ANOVA and the Power model. Results demonstrated that SA55 injection with a Tmaxof 12.6 days and a half-life of 103 days. In conclusion, the SA55 injection demonstrates potential for use in the prevention of COVID-19 infection.
Repetitive magnetic stimulation with iTBS600 induces persistent structural and functional plasticity in mouse organotypic slice cultures
Authors: Lu Han , Garg Shreyash , Lenz Maximilian , Vlachos Andreas 
Published: February 2025

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) is well known for its ability to induce synaptic plasticity, yet its impact on structural and functional remodeling within stimulated networks remains unclear. This study investigates the cellular and network-level mechanisms of rTMS-induced plasticity using a clinically approved 600-pulse intermittent theta burst stimulation (iTBS600) protocol applied to organotypic brain tissue cultures.MethodsWe applied iTBS600 to entorhino-hippocampal organotypic tissue cultures and conducted a 24-hour analysis using c-Fos immunostaining, whole-cell patch-clamp recordings, time-lapse imaging of dendritic spines, and calcium imaging.ResultsWe observed long-term potentiation (LTP) of excitatory synapses in dentate granule cells, characterized by increased mEPSC frequencies and spine remodeling over time. c-Fos expression in the dentate gyrus was transient and exhibited a clear sensitivity to the orientation of the induced electric field, suggesting a direction-dependent induction of plasticity. Structural remodeling of dendritic spines was temporally linked to enhanced synaptic strength, while spontaneous firing rates remained stable during the early phase in the dentate gyrus, indicating the engagement of homeostatic mechanisms. Despite the widespread electric field generated by rTMS, its effects were spatially and temporally precise, driving Hebbian plasticity and region-specific spine dynamics.ConclusionsThese findings provide mechanistic insights into how rTMS-induced LTP promotes targeted plasticity while preserving network stability. Understanding these interactions may help refine stimulation protocols to optimize therapeutic outcomes.