bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration
Authors: Danos Joseph A. , Addemir Merve , McGettigan Lily , Summers Daniel W. 
Published: January 2025

ABSTRACTNeurotrophic factors are critical for establishing functional connectivity in the nervous system and sustaining neuronal survival through adulthood. As the first neurotrophic factor purified, nerve growth factor (NGF) is extensively studied for its prolific role in axon outgrowth, pruning, and survival. Applying NGF to diseased neuronal tissue is an exciting therapeutic option and understanding how NGF regulates local axon susceptibility to pathological degeneration is critical for exploiting its full potential. Our study identifies surprising connections between NGF signaling and proteostasis of axon maintenance factors. NGF deprivation increases Nmnat2 and Stmn2 protein levels in axon segments with a corresponding delay in Wallerian degeneration. Conversely, acute NGF stimulation reduces local abundance of these axon maintenance factors and accelerates Wallerian degeneration. Pharmacological studies implicate phospholipase C as the key effector in TrkA activation, which drives degradation of palmitoylated Stmn2. While seemingly opposed to neuroprotective activities well-documented for NGF, downregulating Nmnat2 and Stmn2 favors axonal outgrowth over transient hyper-susceptibility to Sarm1-dependent degeneration. This new facet of NGF biology has important implications for axonal remodeling during development and sustained integrity through adulthood.
Predictive routing emerges from self-supervised stochastic neural plasticity
Authors: Nejat Hamed , Sherfey Jason , Bastos André M. 
Published: January 2025

AbstractNeurophysiology studies propose that predictive coding is implemented via alpha/beta (8-30 Hz) rhythms preparing specific pathways to process predicted inputs. This leads to a state of relative inhibition, reducing feedforward gamma (40-90 Hz) rhythms and spiking for predictable inputs. This is called predictive routing model. It is unclear which circuit mechanisms implement this push-pull interaction between alpha/beta and gamma rhythms. To explore how predictive routing is implemented, we developed a self-supervised learning algorithm we call generalized Stochastic Delta Rule (gSDR). Development of this algorithm was necessary because manual tuning of parameters (frequently used in computational modeling) is inefficient to search through a non-linear parameter space that leads to emergence of neuronal rhythms. We used gSDR to train biophysical neural circuits and validated the algorithm on simple objectives. Then we applied gSDR to model observed neurophysiology. We asked the model to reproduce a shift from baseline oscillatory dynamics (∼<20Hz) to stimulus induced gamma (∼40-90Hz) dynamics recorded in the macaque visual cortex. This gamma oscillation during stimulation emerged by self-modulation of synaptic weights via gSDR. We further showed that the gamma-beta push-pull interactions implied by predictive routing could emerge via stochastic modulation of the local circuitry as well as top-down modulatory inputs to a network. To summarize, gSDR succeeded in training biophysical neural circuits to satisfy a series of neuronal objectives. This revealed the inhibitory neuron mechanisms underlying the gamma-beta push-pull dynamics that are observed during predictive processing tasks in systems and cognitive neuroscience.Significant StatementThis study contributes to the advancement of self-supervised learning for modeling the behavior of complex neural circuits and specifically, biophysical modeling. We performed simulations in order to examine basic mechanisms in predictive routing framework. Since generalized stochastic delta rule (gSDR) is in the family of evolutionary algorithms and does not rely on specific model-based assumptions, it could improve computational neuroscience studies by adding autonomous approaches in neural network research with emphasis on neurobiology. In addition, it is allows to expand bio-plausibility by defining multiple objectives, making it capable of expanding its neurobiological constraints.
Nurr1 orchestrates claustrum development and functionality
Authors: Yan Kuo , Newman Andrew , Lange Pauline , Mueller Susanne , Foddis Marco , Mantwill Maron , Finke Carsten , Koch Stefan Paul , Boehm-Sturm Philipp , Deng Penghui , Long Melissa , Tarabykin Victor 
Published: January 2025

AbstractClaustrum is the part of the forebrain known to be most widely interconnected tissue with almost all global regions. It is believed to be involved in coordinating multiple cognitive behaviors including consciousness formation. However, little is known about the molecular mechanisms underlying its development and involvement in behavioral control. Here we show that Nurr1 (Nr4a2) is the key transcription factor orchestrating claustral morphogenesis, functional connectivity and thus behaviors. Nurr1 deficient claustral cells aberrantly migrate into insular cortex, shaping claustrum into an abnormal wing-like structure, and ectopically turn on insular corticex genetic program. Accordingly, functional connectivity of the claustrum is not properly formed and relevant behaviors are dysregulated in Nurr1 deficient mice. We show that Nurr1 regulates claustral neuron positioning by suppressing G-protein signaling.
Detection of HTTex1p by western blot and immunostaining of HD human and mouse brain using neo-epitope antibody P90 highlights impact of CAG repeat expansion on its size, solubility, and response to MSH3 silencing
Authors: Sapp Ellen , Boudi Adel , Iwanowicz Andrew , Belgrad Jillian , Miller Rachael , O’Reilly Daniel , Yamada Ken , Deng Yunping , Joni Marion , Li Xueyi , Kegel-Gleason Kimberly , Khvorova Anastasia , Reiner Anton , Aronin Neil , DiFiglia Marian 
Published: January 2025

AbstractHTT1ahas been identified in human and mouse HD brain as the pathogenic exon 1 mRNA generated from aberrant splicing between exon 1 and 2 that contributes to aggregate formation and neuronal dysfunction (Sathasivam et al., 2013). Detection of the HTT exon 1 protein (HTTex1p) has been accomplished with surrogate antibodies in fluorescence-based reporter assays (MSD, HTRF), and immunoprecipitation assays, in HD postmortem cerebellum and knock-in mice but direct detection by SDS-PAGE and western blot assay has been lacking. Here proteins in subcellular fractions prepared from human and mouse HD brain were separated by SDS-PAGE and probed by western blot with neo-epitope monoclonal antibodies (P90-1B12 and 11G2) directed to the C-terminal 8 residues of HTTex1p. In human HD putamen and cortex, HTTex1p migrated at 56-60 kD and at higher molecular masses (HMM) consistent with the presence of CAG repeat expansion inHTT1a. HTTex1p in control brain was low or undetectable. Immunofluorescence labeling of human HD cortex using P90-11G2 revealed small aggregates that sparsely populated the neuropil in layers 3 and 5. In caudate putamen of 6 month old HD knock-in mice (Q50, Q80, Q111, Q140 and Q175) HTTex1p migration was inversely correlated with CAG repeat length and appeared as a SDS soluble high molecular mass (HMM) smear in HD Q111, Q140 and Q175 mice but not in Q50 and Q80 mice indicating a CAG repeat size threshold for detecting HTTex1p aggregation. Migration of HTTex1p and HMM smear changed with age in caudate putamen of Q111, Q175 and YAC128 mice. Treating HD Q111 mice with siRNA to MSH3, a modifier of CAG repeat expansion, significantly reduced levels of the HMM smear indicating that the effects of curbing CAG repeat expansion was quantifiable. These results show that P90 antibodies can be used in western blot assays and immunostaining to track and quantify HTTex1p levels, subcellular localization, and solubility.
Cortical responses to conflicting binocular stimuli in mouse primary visual cortex
Authors: Montgomery D. P. , Bowen D. A. , Wu J. , Bear M. F. , Gaier E. D. 
Published: January 2025

AbstractBinocular vision requires that the brain integrate information coming from each eye. These images are combined (fused) to generate a meaningful composite image. Differences between images, within a range, provide useful information about depth (stereopsis). Interocular disparities that are not effectively combined result in diplopia and rivalry. The neural mechanisms underlying these binocular interactions remain poorly understood. Using a combination of visually evoked potential (VEP) recordings, unit recordings, and 2-photon calcium imaging in the binocular region of mouse primary visual cortex (bV1), we probed the neural mechanisms underlying the processing of two distinct forms of disparate binocular signals. Using a dichoptic display, introduction of a spatial interocular phase disparity in grating stimuli reduced VEP magnitude through decreased neuronal firing in the early phase of the response (40-80 ms after stimulus onset, corresponding to the VEP negativity). Introduction of an interocular orientation disparity also decreased VEP magnitude, but this difference was driven by an increase in firing in the late portion of the visual response (100-200 ms after stimulus onset, corresponding to the VEP positivity). This increase in activity was observed for both regular-spiking (putative excitatory) and fast-spiking (putative parvalbumin-positive inhibitory) units. By contrast, visually evoked calcium responses of somatostatin-positive interneurons decreased with introduction of the interocular orientation disparity. Based on these results, we propose that interocular phase differences largely suppress bV1 responses via feedforward thalamocortical interactions, whereas interocular orientation differences prolong visually evoked activity in bV1 through somatostatin-positive interneuron-mediated disinhibition.
Rotationally Stable Dynamics Over Long Timescales Emerge in Neuronal Development
Authors: Burrows Dominic R.W. , Rosch Richard E. 
Published: January 2025

AbstractNeuronal networks must balance the need for stable yet flexible dynamics. This is evident during brain development, when synaptic plasticity during critical windows enables adaptability to changing environments whilst ensuring the stability of population dynamics. The emergence of population dynamics that balance stability and flexibility during development is poorly understood. Here, we investigated developmental brain dynamics in larval zebrafish, usingin vivo2-photon imaging to record single-cell activity across major brain regions from 3-8 days post-fertilisation, a highly plastic period in which hunting behaviours are established. Our findings revealed region-specific trajectories in the development of such dynamic regimes: the telencephalon exhibited increased neuronal excitability and long-range correlations, alongside the emergence of scale invariant avalanche dynamics indicative of enhanced flexibility. Conversely, while other regions showed increased state transitions over development, the telencephalon demonstrated a surprising rise in state stability, characterized by slightly longer dwell times and drastically reduced angular velocity in state space. Remarkably, such rotationally stable dynamics persisted up to 5 seconds into the future, indicating the emergence of strong attractors supporting stability over long timescales. Notably, we observed that telencephalon dynamics were maintained near to but not at a phase transition, thus allowing for robust responses while remaining adaptable to novel inputs. Our results highlight regionally-specific trajectories in the relationship between flexibility and stability, illustrating how developing neuronal populations can self-organize to balance these competing demands.Significance StatementBrain networks must balance the flexibility to adapt to new stimuli with the need for stability. This trade-off is particularly important during periods of high plasticity in brain development. Our study investigates this balance by recording single-cell activity across the entire brain of developing larval zebrafish. We discovered that brain dynamics become increasingly diverse, characterized by both short and long bursts of activity, reflecting increased flexibility. Simultaneously, we observed the emergence of stable dynamics, linked to consistent activity patterns over time. Using a modelling approach, we showed that this stability was driven by the formation of stable attractors that shape the dynamic trajectories. These findings highlight how population mechanisms can shape the dynamic interplay between flexibility and stability in regional networks in the developing brain.
Impact of Segmentation Errors in Analysis of Spatial Transcriptomics Data
Authors: Mitchel Jonathan , Gao Teng , Cole Eli , Petukhov Viktor , Kharchenko Peter V. 
Published: January 2025

AbstractSpatial transcriptomics aims to elucidate cell coordination within biological tissues by linking the state of the cell with its local tissue microenvironment. Imaging-based assays are particularly promising for exploring such interdependencies, as they can resolve molecular and cellular features with subcellular resolution in three dimensions. Quantification and analysis of cellular state in such data, however, ultimately depends on the ability to recognize which molecules belong to each cell. Despite computational and experimental progress, this cell segmentation task remains challenging. Here we re-analyze data from multiple tissues and platforms and find that segmentation errors currently confound most downstream analysis of cellular state, including analysis of differential expression, inference of neighboring cell influence, and ligand-receptor interactions. The extent to which mis-segmented molecules impact the results can be striking, often dominating the set of top hits. We show that factorization of molecular neighborhoods can be effective at isolating such molecular admixtures and minimizing their impact on downstream analysis, analogous to doublet filtering of scRNA-seq data. As applications of spatial transcriptomics assays become more widespread, we expect corrections for the confounding effect of segmentation errors to become increasingly important for being able to resolve molecular mechanisms of tissue biology.
Changes in blowfly (Diptera: Calliphoridae) wing morphology during succession in rat carcasses across forest and grassland habitats in South Brazil
Authors: Colares Lucas Ferreira , Herdina Anita da Silva , Bender Mariana , Dambros Cristian de Sales 
Published: January 2025

AbstractSuccession is one of the most extensively studied ecological phenomena, yet debates persist about the importance of dispersal and external factors in driving this process. We aimed to quantify the influence of these factors by investigating how wing‐related traits evolve across succession of blowfly (Diptera: Calliphoridae) communities in South Brazil. Rat carrion was placed in both forest and grassland habitats, and the associated blowfly communities were documented throughout the decomposition process. Using morphometric analysis, we measured wing and thorax traits and assessed trait changes over succession through mixed models. Our findings revealed that carrion succession follows distinct trajectories in forest and grassland environments. Specifically, we observed that Calliphora lopesi predominantly visited carcasses during the final phase of decomposition, resulting in significant differences in species composition and wing size between habitats. In forests, wing size increased toward the later stages of succession, whereas an opposite trend was observed in grasslands. Notably, these trait patterns were only evident at the species level, indicating that intraspecific trait variation is irrelevant. Stronger dispersers tend to arrive during the later stages of succession, suggesting that dispersal has a negligible role in shaping successional dynamics. Instead, environmental differences between habitats drive trait patterns throughout succession. Our results suggest that community composition in ephemeral resources is governed by deterministic processes and that successional stages can be predicted based on blowfly wing traits. Specifically, the presence of the large‐winged C. lopesi indicates late decay, while the small‐winged Chrysomia albiceps and Lucilia eximia are indicative of early decay.
Identifying ENO1 as a protein target of chlorogenic acid to inhibit cellular senescence and prevent skin photoaging in mice
Authors: He Xueling , Wang Chen , Zhang Qianyu , Yang Tong , Guo Qiuyan , Wang Yaxu , Guo Jiayue , Wang Pengjie , Zhang Junzhe , Tang Huan , Zhu Yinhua , Wang Jigang 
Published: January 2025

AbstractCellular senescence plays a critical role in repeated ultraviolet (UV) exposure‐induced skin photoaging. Currently, from the perspective of regulating senescent cells, potent compounds or reliable protein targets that could effectively prevent skin photoaging have not yet been reported. Herein, we demonstrated that chlorogenic acid (CGA) significantly inhibited UVA‐induced senescence of human dermis skin fibroblasts (HDF) cells by screening the natural product library. The activity‐based protein profiling (ABPP) result revealed that Enolase 1 (ENO1) is one of the direct targets of CGA in HDF cells. Further mechanism research indicated that CGA covalently binds to ENO1, and prevented UVA‐induced cellular senescence by suppressing the activity of ENO1 protein to block the glycolytic pathway. Importantly, we found that CGA dose‐dependently reduced the skin wrinkle score, alleviated skin pathological features and inhibited senescent characteristics in a photoaging mouse model. The proteomic analysis revealed that CGA treatment effectively inhibited senescence‐associated secretory phenotype (SASP) secretion and glycolysis in skin samples of mice. Collectively, our study not only demonstrated that inhibiting cell senescence is an effective anti‐skin photoaging strategy, but also revealed that ENO1 is a promising protein target to prevent photoaging.
Efficiency of dung beetles (Coleoptera: Scarabaeidae) in improving soil and forage grasses by incorporating nutrients through the removal of cattle dung
Authors: Niero Mariana Mrotskoski , Loss Arcângelo , Brunetto Gustavo , Hernández Malva Isabel Medina 
Published: January 2025

AbstractCoprophagous dung beetles provide important ecosystem services in improving soil quality and plant development in agricultural environments due to the availability of nutrients from dung removal. The study aimed to compare the effect of dung removal performed by two functional groups, among themselves and with mineral fertiliser, on improving soil and forage grass characteristics. An experiment in mesocosms was conducted in Southern Brazil during the summer/autumn of 2021, sowing Urochloa brizantha in the treatments: (1) telecoprid species (Canthon rutilans cyanescens), (2) paracoprid species (Dichotomius sericeus), (3) both species together, (4) mineral fertiliser and control with cattle dung. Dung removal was quantified weekly. At the end of the experiment, the soil's physical, chemical and microbiological characteristics, dry biomass and macronutrients (N, P and K) of the leaves and roots, and photosynthetic pigments of grasses were analysed. The dung beetle species studied increased total nitrogen and organic matter contents and their particulate fractions of C and N. Paracoprids decreased the soil bulk density and improved its soil aggregation, influencing the pH and Mg contents, with a reduction in Al levels. They were as efficient as mineral fertiliser in incorporating K into the soil. Treatments with beetles had values similar to mineral fertiliser in the foliar concentrations of P, and paracoprids promoted increases in the K concentration in the leaves and roots of the grass. This functional group was also more efficient in removing cattle dung, which was positively related to the amounts of N, organic matter and its particulate fractions, P, macroaggregates and the cation exchange capacity (CECpH7.0) of the soil. Thus, dung removal was associated with improvement in the soil, mainly paracoprids, reinforcing the importance of the ecosystem functions performed by these organisms in agricultural environments, where they can contribute to the increase in nutrient cycling with a consequent decrease in the use of mineral fertilisers.
Gender Under Scrutiny – Whose Gender?
Authors: Mackay Finn 
Published: January 2025

AbstractThis article will argue that there is no war on gender, in the context of the so‐called ‘gender wars’. The dominant binary model of gender as male, masculine, heterosexual or female, feminine, heterosexual is not under scrutiny. There is an old and ongoing attempt to control sex, gender and sexuality and constrain and construct what these mean for the benefit of the patriarchal status quo. Rather than a war on gender, there is a war on identities, relationships and families that are the ‘wrong’ gender, other to the heterosexual nuclear family.
New Insights on Continuous Renal Replacement Therapy for Acute Respiratory Distress Syndrome: A Systematic Review and Meta‐Analysis
Authors: Zeng Siyao , Cui Shanpeng , Li Yue , Yao Zhipeng , Li Yunlong , Cao Yang , Wen Lianghe , Li Ming , Zheng Junbo , Wang Hongliang 
Published: January 2025

ABSTRACTBackgroundIn recent times, the applications of continuous renal replacement therapy (CRRT) beyond kidney‐related conditions have been progressively increasing, and its implementation in randomized controlled trials (RCTs) specifically for acute respiratory distress syndrome (ARDS) has been documented. This meta‐analysis compiles all existing RCTs to assess whether CRRT benefits ARDS.MethodsWe searched 12 databases in English and Chinese and two clinical trial centers up to November 28, 2023. The main outcome indicator is the mortality rate. Secondary outcome indicators include incidence of ventilator‐associated pneumonia (VAP), ICU length of stay, mechanical ventilation time, oxygenation index (OI) at 24 h (h), OI at 48 h, OI at 72 h, OI at 7 days (d), partial pressure of oxygen (PaO2) at 72 h, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24 h, APACHE II score at 48 h, APACHE II score at 72 h, APACHE II score at 7 d, extravascular lung water indexes (EVLWI) at 72 h, TNF‐α at 24 h, TNF‐α at 7 d, IL‐6 at 24 h, IL‐6 at 48 h, IL‐6 at 72 h, and IL‐6 at 7 d. Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95% confidence intervals (95% CI).ResultsWe summarized 36 studies, including 2123 patients. It was found that for ARDS, using CRRT in addition to conventional therapy can reduce the mortality rate (I2 = 0%; RR: 0.40; 95% CI: 0.30–0.53; p < 0.01), the incidence of VAP (I2 = 0%; RR: 0.44; 95% CI: 0.33–0.59; p < 0.01), ICU length of stay, mechanical ventilation time, and EVLWI at 72 h, as well as APACHE II score, TNF‐α, and IL‐6 at various time points. Additionally, it can increase OI during different time intervals and PaO2 at 72 h.ConclusionsLow‐quality evidence suggests that compared with conventional therapy alone, the use of CRRT may be associated with a lower mortality rate, the incidence of VAP, ICU length of stay, mechanical ventilation time, EVLWI, APACHE II score, TNF‐α, and IL‐6 and may be related to better respiratory function. CRRT may be beneficial for ARDS patients. Future multicenter, well‐designed, high‐quality RCTs are needed to substantiate these findings.