bluuebunny/crossref_metadata_2025_split huggingface dataset:
R183Q GNAQ Sturge–Weber Syndrome Leptomeningeal and Cerebrovascular Developmental Mouse Model
Authors: Solomon Chase , McCann Meghan , Singh Pratibha , Nemeth Christina , Comi Anne 
Published: September 2024

Objective(s):
Sturge–Weber syndrome (SWS), a rare neurovascular malformation disorder, is usually caused by the R183Q GNAQ somatic mosaic mutation enriched in brain endothelial cells. A developmental mouse model of SWS brain involvement is needed to investigate mutation impact upon brain vascular development and to facilitate preclinical drug studies.

Methods:
A new Tet-ON R183Q GNAQ transgenic mouse line was paired with rtTA tet transactivator mice under the Tie2 promoter to generate mice expressing endothelial R183Q GNAQ in the presence of doxycycline. Litters were perfused at P14-17; half received a subseizure dose (1.5 mg/kg; intraperitoneal) of kainate an hour before perfusion. A subset was perfused with Evans blue. Fixed mouse brains were stained with X-gal, DAPI, and antibodies for Gαq, Tie2, phosphorylated-S6, and claudin-5. Images were scored for vessel staining intensity.

Results:
X-gal staining was seen only in mutant mice; leptomeningeal endothelial X-gal staining was more frequent in kainate-treated mice (P < 0.001). When perfused with Evans blue, only mutant brains showed severe staining (P = 0.028). Median phosphorylated-S6 vessel scores were significantly higher in the leptomeninges of mutant mice (P = 0.035). Mutant cortical microvessels demonstrated discontinuous claudin-5 and phosphorylated-S6 staining as well as increased vessel length in kainate-treated mice (P = 0.024).

Conclusions:
The new R183Q GNAQ Tet-ON developmental mouse brain model of SWS demonstrates endothelial expression of mutant Gαq associated with blood–brain barrier breakdown, altered vascular mammalian target of rapamycin activity, and abnormal cortical microvessel structure. This new translational model can be used to develop new drug targets and treatments for SWS.
Clinical Features, Management, and Recurrence of Acute Ischemic Stroke Occurring in Patients on Oral Anticoagulant Treatment for Nonvalvular Atrial Fibrillation
Authors: Grifoni Elisa , Pagni Beatrice , Sansone Teresa , Baldini Mariella , Bertini Elisabetta , Giannoni Sara , Di Donato Ilaria , Sivieri Irene , Iandoli Gina , Mannini Marianna , Giglio Elisa , Vescera Vincenzo , Brai Eleonora , Signorini Ira , Cosentino Eleonora , Micheletti Irene , Cioni Elisa , Pelagalli Giulia , Dei Alessandro , Giordano Antonio , Dainelli Francesca , Romagnoli Mario , Mattaliano Chiara , Schipani Elena , Murgida Giuseppe Salvatore , Di Martino Stefania , Francolini Valentina , Masotti Luca 
Published: September 2024

Objectives:
The optimal management of acute ischemic stroke (AIS) in patients with oral anticoagulation (OA) is challenging. Our study aimed to analyze the clinical characteristics and outcome of AIS in patients with OA for nonvalvular atrial fibrillation (NVAF).

Methods:
We retrospectively analyzed data on NVAF patients with AIS on direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) admitted to our Stroke Unit from 2017 to 2022. Ninety-day modified Rankin Scale (mRS), 90-day, and 12-month stroke recurrences were recorded.

Results:
A total of 169 patients (53.2% female, mean age 82.8±6.7 y), 117 (69.2%) on DOAC, and 52 on VKA (30.8%), were enrolled. Mean age, in-hospital mortality, and 90-day mRS ≥4 were significantly higher in VKA patients. 63.4% of VKA patients had subtherapeutic INR, whereas 47.1% of DOAC patients were on low-dose (14.2% off-label). Large vessel occlusion and embolic etiology were more frequent in VKA patients (34.6% vs. 26.4%, P=0.358; 92.3% vs. 74.3%, P=0.007, respectively), whereas lacunar strokes were more frequent in DOAC patients (19.8% vs. 12.2%, P=0.366). Among patients on VKA before AIS 86.4% were switched to DOAC, whereas a DOAC-to-VKA and a DOAC-to-DOAC switch were done in 25.4% and 11.7%, respectively. Stroke recurrence occurred in 6.4% of patients at 90 days and 10.7% at 12 months. Anticoagulant switching was not associated with stroke recurrences.

Conclusions:
In our study, nonembolic etiology was more frequent in DOAC patients and anticoagulant switching did not reduce the risk of stroke recurrence. Prospective multicentric studies are warranted.
The effects of extracorporeal shock wave therapy on cutaneous radiation injury in a mouse model
Authors: Park Sang Woo , Shin Jaebong , Jeong Bae Kwon , Byun Sangjun , Lee Kyung Suk , Choi Jaehoon 
Published: September 2024

Background:
Although radiation-induced skin injuries are a concern in patients receiving radiation therapy, there are few effective treatments. The aim of this study was to evaluate the protective effects of extracorporeal shock wave therapy (ESWT) on irradiated fibroblasts and mouse skin.

Methods:
In the in vitro study of human dermal fibroblasts, the experimental group was subjected to ESWT following irradiation (20 Gy). The control groups were only irradiated or only subjected to ESWT. At 24 or 48 h post-ESWT, cell viability, cell migration, and mRNA and protein expression were measured. In the in vivo study, the experimental group (7 mice) was treated with ESWT following irradiation (45 Gy). The control group (7 mice) was only irradiated. At 8 weeks post-irradiation, dorsal skin was harvested for histopathologic examination and protein isolation.

Results:
In dermal fibroblasts, treatment with ESWT increased viability of irradiated cells compared with irradiated-only and untreated cells (p = 0.005). ESWT increased cell migration 24 h post-irradiation (p = 0.002), and decreased TGF-β1 protein expression 48 h post-irradiation (p = 0.024). In mice, ESWT decreased the level of radiation-related skin injury (p = 0.006). Treatment of irradiated skin with ESWT decreased TGF-β1 (p = 0.009) and phospho-Smad3 (p = 0.009) protein expression, as well as decreasing myofibroblasts (p = 0.047) and increasing vessel density (p < 0.001).

Conclusions:
Our study demonstrated that ESWT alleviated radiation-induced fibrosis by downregulating TGF-β1 expression. It suggests the potential of ESWT for the treatment of radiation-induced fibrosis.
Psilocybin prevents habituation to familiar stimuli and preserves sensitivity to sound following repeated stimulation in mouse primary auditory cortex
Authors: Lane Conor P. , Tarka Veronica M. , Valentin Olivier , Lehmann Alexandre , Hamel Edith , de Villers-Sidani Etienne 
Published: September 2024

AbstractPsilocybin, a psychoactive substance derived from fungi, has been utilized historically by diverse cultures for both medicinal and non-medicinal purposes, owing to its ability to elicit profound sensory and cognitive alterations and sustain long-term changes in mood and cognition. Promising results from recent clinical studies have generated a wave of interest in employing psilocybin to treat neuropsychiatric and neuro-degenerative conditions. How psychedelics cause acute perceptual effects, and how these relate to long-lasting alterations is still debated. Whereas it is thought that perceptual disturbances may be caused by disrupted flow of information between sensory and higher order areas,in vivostudies have focused mostly on the latter. In particular, there has been little study of how psilocybin affects sensory representations in primary auditory cortex (A1). We used two-photon microscopy and wide field calcium imaging to examine how psilocybin affects A1 neuron response properties in the mouse. Administration of 1 mg/kg psilocybin prevented habituation of sound-evoked responses to repeated stimuli, maintaining overall responsiveness, bandwidth, and sound-level response thresholds after repeated stimulation. This was in contrast to marked habituation of responses and narrowing of tuning in controls. We observed no effect on overall distribution of best frequencies at the cortical level, suggesting psilocybin in A1 disrupts normal sensory gating, rather than tonotopic organization. This supports models of psychedelic action in which perceptual disturbances are driven by disrupted hierarchical sensory gating. With further research, influences of psychedelics on sensory representations could be harnessed to target maladaptive sensory processing in conditions such as tinnitus.Significance StatementDespite its role in altering auditory sensory perception, the impact of psilocybin on modulating neuronal activity in the auditory cortex remains understudied. This study is the first to identify an inhibition of normal auditory habituation to repeated stimuli with single-neuron resolution. We identify a role for psilocybin in the targeted, context-dependent modulation of auditory sensory neural tuning properties, which may help to explain how disruption of hierarchical control of sensory representations leads to perceptual disturbances. With further work, this influence on sensory representations could be used to target conditions where maladaptive sensory processing leads to deleterious health outcomes.
Effect of aging andVarroaparasitism on the paracellular and transcellular permeability of the honeybee blood-brain barrier
Authors: Quigley Tyler , Amdam Gro 
Published: September 2024

AbstractHoneybees (Apis mellifera) provide crucial pollination services to agricultural systems globally, however, their healthspan in these contexts is constantly at risk. Agricultural environments impose a variety of sublethal stressors onto honeybees, including parasites, pathogens, pesticides, and poor nutrition. Synergies between age, age-associated tasks, and these stressors are believed to underlie colony failure trends of the past decade. Identifying the mechanisms by which age and stressors impact honeybee physiology is an important priority in protecting honeybee and other pollinator populations. An underexplored physiological structure in honeybees is the blood-brain barrier, a protective layer of cells that surround the brain. Here, we assess a key dimensions of blood-brain barrier function, paracellular and transcellular permeability to molecules in the hemolymph. We assess these modes of permeability in multiple age groups and after exposure to varying levels of infestation by the parasitic miteVarroa destructorduring development. Our results demonstrate that the paracellular permeability of the honeybee blood-brain barrier is stable across their lifespan and uponVarroaexposure. In contrast, we found that transcellular permeability is increased in honeybees exposed to a highVarroaload. These results demonstrate how age and stress variably impact a primary protective structure of the honeybee central nervous system, which may lead to targeted interventions for protecting honeybee healthspan. The assay developed here may be easily applied to different aging- and stress contexts, further enabling studies focused on understanding maintenance and decline of the honeybee blood-brain barrier.
The Virtual Plant Laboratory: a modern plant modeling framework in Julia
Authors: Morales Alejandro , Kottelenberg David B. , Ernst Ana , Vezy Rémi , Evers Jochem B. 
Published: September 2024

AbstractThe Virtual Plant Laboratory (VPL) is a novel software for building, simulating, and visualizing functional- structural plant (FSP) models. FSP models focus on the interactions between plant structure, internal physiological processes, and the biotic and abiotic environment. VPL is built in the Julia programming language and is designed to be a flexible and extensible platform for FSP modeling. Using Julia brings the advantage that only one programming language is required for the whole modeling cycle as Julia is as fast as compiled languages but also dynamic as interpreted languages. VPL provides a graph rewriting system for building dynamic models of plant growth and development, an interactive 3D visualization system and a Monte Carlo ray tracer for simulating radiation interception by plant canopies. In this paper, we introduce VPL, highlighting the main components, modeling paradigms, and design decisions behind it, as well as a future roadmap for further development. We also present a short case study of a model for intercropping of legumes and cereals that was built fully with VPL, as an example of what can be built with this software. VPL is fully open source and available in all common computing platforms for anyone to use. Full documentation and tutorials are available athttps://virtualplantlab.com.
MPCD Index for Hepatocellular Carcinoma Patients Based on Mitochondrial Function and Cell Death Patterns
Authors: Wang Long-Xing , Zhao Zhi-Ming , Shu Kun-Xian , Ma Ming-Yue 
Published: September 2024

AbstractHepatocellular carcinoma (HCC) is a highly heterogeneous cancer with a poor prognosis. During the development of cancer cells, mitochondria influence various cell death patterns by regulating metabolic pathways such as oxidative phosphorylation. However, the relationship between mitochondrial function and cell death patterns in HCC remains unclear. In this study, we used a comprehensive machine learning framework to construct a mitochondrial functional activity-associated programmed cell death index (MPCDI) based on scRNA-seq and RNA-seq data from TCGA, GEO, and ICGC datasets. The index signature was used to classify HCC patients, and studied the multi-omics features, immune microenvironment, and drug sensitivity of the subtypes. Finally, we constructed the MPCDI signature consisting of four genes (S100A9,FYN,LGALS3, andHMOX1), which was one of the independent risk factors for the prognosis of HCC patients. The HCC patients were divided into high- and low-MPCDI groups, and the immune status was different between the two groups. Patients with high MPCDI had higher TIDE scores and poorer responses to immunotherapy, suggesting that high-MPCDI patients might not be suitable for immunotherapy. By analyzing the drug sensitivity data of CTRP, GDSC, and PRISM databases, it was found that staurosporine has potential therapeutic significance for patients with high MPCDI. In summary, based on the characteristics of mitochondria function and PCD patterns, we used single-cell and transcriptome data to identify four genes and construct the MPCDI signature, which provided new perspectives and directions for the clinical diagnosis and personalized treatment of HCC patients.
ACOUSTIC PARAMETER COMBINATIONS UNDERLYING MAPPING OF AUDITORY PSEUDOWORD SOUNDS TO MULTIPLE DOMAINS OF MEANING: A MACHINE LEARNING APPROACH
Authors: Kumar G. Vinodh , Lacey Simon , Dorsi Josh , Nygaard Lynne C. , Sathian K. 
Published: September 2024

ABSTRACTSound symbolism, referring to the resemblance between the sound structure of words and their meaning, is commonly studied using auditory pseudowords. Companion studies across seven meaning domains demonstrated systematic relationships, varying by domain, between the perceptual ratings, phonetic features, and acoustic parameters of a set of 537 pseudowords (Lacey et al. 2024a, 2024b). Here we employed a k-nearest-neighbor (KNN) machine-learning algorithm to compare 4094 combinations of twelve acoustic parameters (3 spectro-temporal and 9 characterizing vocal quality) and identify the parameter combination that best predicted perceptual ratings in each domain. Using multiple regression, we then examined the relative contributions of the parameters comprising the best performing acoustic model for each domain. Finally, we used the KNN approach to generate sound-symbolic ratings, in the shape domain, for 160 real words and compared these predicted ratings with corresponding perceptual ratings. We found that sound-symbolic mappings rely on domain-specific combinations and weights of acoustic parameters. One spectro-temporal parameter, the fast Fourier transform, and one vocal parameter, the fraction of unvoiced frames, were both present in the best performing model for each meaning domain studied, indicating the general importance of these two parameters for sound-symbolic judgments. The predicted and perceptual ratings of the real words were strongly correlated, indicating the value of this approach to measure the degree of sound-symbolic mapping in natural languages, unconfounded by semantic bias. Our findings support the proposed relevance of sound symbolism to language.
LC8 enhances 53BP1 foci through heterogeneous bridging of 53BP1 oligomers
Authors: Howe Jesse , Walker Douglas , Tengler Kyle , Sonpatki Maya , Reardon Patrick , Leung Justin W.C. , Barbar Elisar J. 
Published: September 2024

Abstract53BP1 is a key player in DNA repair and together with BRCA1 regulate selection of DNA double strand break repair mechanisms. Localization of DNA repair factors to sites of DNA damage by 53BP1 is controlled by its oligomerization domain (OD) and binding to LC8, a hub protein that functions to dimerize >100 clients. Here we show that 53BP1 OD is a trimer, an unusual finding for LC8 clients which are all dimers or tetramers. As a trimer, 53BP1 forms a heterogeneous mixture of complexes when bound to dimeric LC8 with the largest mass corresponding to a dimer-of-trimers bridged by 3 LC8 dimers. Analytical ultracentrifugation and isothermal titration calorimetry demonstrate that only the second of the three LC8 recognition motifs is necessary for a stable bridged complex. The stability of the bridged complex is tuned by multivalency, binding specificity of the second LC8 site, and the length of the linker separating the LC8 binding domain and OD. 53BP1 mutants deficient in bridged species fail to impact 53BP1 focus formation in human cell culture studies, suggesting that the primary role of LC8 is to bridge 53BP1 trimers which in turn promotes recruitment of 53BP1 at sites of DNA damage. We propose that the formation of higher-order oligomers of 53BP1 explains how LC8 elicits an improvement in 53BP1 foci and affects the structure and functions of 53BP1.
The Interplay of Perceived Mental Health and Suicidal Ideation among Aboriginal Peoples in Canada: A Secondary Analysis of Aboriginal Peoples Survey
Authors: Adebayo Olasehinde Ben 
Published: September 2024

AbstractThe disproportionately high suicide rates among Aboriginal populations in Canada, linked to historical trauma and systemic inequities, necessitate targeted mental health interventions. This study investigated the relationship between perceived mental health and suicidal ideation among the Aboriginal population in Canada, First Nations, Inuit, and Métis, using data from the 2012 Aboriginal Peoples Survey (APS) (n=4,725). The analysis employed chi-square tests and bivariate logistic regression to examine the association between self-perceived mental health, suicidal ideation, and socio-demographic factors. Results revealed significant associations between suicidal ideation, age group (p<.001), and sex (p<.001), with younger individuals (18-24 years) and females reporting a higher prevalence of suicidal thoughts. Also, bivariate logistic regression showed that being between the ages of 25 and 34 was a strong predictor of suicidal thoughts (OR = 1.954, p =.000), while being female (OR =.648, p =.000) and having a higher socioeconomic status (OR =.678, p =.000) were weaker predictors. Although Aboriginal identity was not significantly associated with suicidal ideation, self-perceived mental health was. These results made it clear that focused and targeted mental health interventions and culturally appropriate suicide prevention strategies are needed right away in Aboriginal communities in Canada. These strategies need to meet the needs of vulnerable groups, like younger people and women.
Single-cell proteomics of pre-implantation mouse embryos uncovers distinct asymmetry of certain proteins among early blastomeres
Authors: Yuan Yuan , Hu Mo , Zheng Yinghui , Zhang Yutong , Pang Yuxuan , Xie Xiaoliang Sunney 
Published: September 2024

AbstractDuring pre-implantation mouse embryonic development, blastomeres undergo division and differentiation, reaching a distinctive level of heterogeneity, hence the completion of the first cell fate determination. However, when the initial asymmetry emerges and how this heterogeneity amplifies, particularly at the protein level, remain elusive. Here, by mass spectrometry-based single-blastomere proteomics, we identified proteins exhibiting significant heterogeneity in abundance among mouse blastomeres as early as the 2-cell stage. Differential gene expression among blastomeres, as indicated by intra-embryo variation in RNA abundance detected through single-cell RNA sequencing, was insufficient to fully explain the corresponding disparities in protein abundance. Instead, the asymmetric distribution of protein molecules during cell division was observed, serving as another mechanism contributing to protein heterogeneity, independent of RNA expression.
Genetic dissection of MutL complexes in Arabidopsis meiosis
Authors: Kbiri Nadia , Fernández-Jiménez Nadia , Dziegielewski Wojciech , Sáez-Zárate Esperanza , Pelé Alexandre , Mata-Villanueva Ana , Santos Juan L. , Pradillo Mónica , Ziolkowski Piotr A. 
Published: September 2024

ABSTRACTDuring meiosis, homologous chromosomes exchange genetic material through crossing-over. The main crossover pathway relies on ZMM proteins, including ZIP4 and HEI10, and is typically resolved by the MLH1/MLH3 heterodimer, MutLγ. Our analysis of plant fertility and bivalent formation revealed that the MUS81 endonuclease can partially compensate for the MutLγ loss. Comparing genome-wide crossover maps of themlh1mutant with ZMM-deficient mutants and lines with varying HEI10 levels reveals that while crossover interference persists inmlh1, it is weakened. Additionally,mlh1show reduced crossover assurance, leading to a higher incidence of aneuploidy in offspring. This is likely due to MUS81 resolving intermediates without the crossover bias seen in MutLγ. Comparingmlh1 mlh3 mus81andzip4 mus81mutants suggests that additional crossover pathways emerge in the absence of both MutLγ and MUS81. The loss of MutLγ can also be suppressed by eliminating the FANCM helicase. Elevated expression ofMLH1orMLH3increases crossover frequency, while their overexpression significantly reduces crossover numbers and plant fertility, highlighting the importance for tight control of MLH1/MLH3 levels. By contrast, PMS1, a component of the MutLα endonuclease, appears not to be involved in crossing-over. Together, these findings demonstrate the unique role of MutLγ in ZMM-dependent crossover regulation.