Biology subjects

Richard, C.

Publications and source records attributed to Richard, C..

9 recordsLinked to original sources

bioRxiv2026

Voluntary wheel running selectively preserves skeletal muscle during pancreatic cancer cachexia despite persistent systemic alterations

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with cancer cachexia, involving alterations across multiple physiological systems. Whether distinct exercise paradigms similarly influence these compartments remains unclear. We compared voluntary wheel running (VWR) and treadmill running (TR) using an integrative physiological approach in a murine model of pancreatic cancer cachexia. Methods Male C57BL/6J mice bearing UN-KC-6141 pancreatic tumor cells were allocated to inactive control (CaCTL), VWR or TR groups and compared with healthy controls. Tumor progression, body composition, skeletal muscle, adipose tissue, hepatic metabolism, systemic inflammation, energy expenditure and behavior were assessed. Analysis of covariance determined whether tissue-mass differences remained evident after adjustment for tumor burden. Results UN-KC-6141 tumors induced a systemic cachectic phenotype involving skeletal muscle and adipose tissue wasting, hepatic metabolic remodeling, systemic inflammation and behavioral alterations. VWR slowed tumor growth, reduced final tumor mass, improved the body-weight trajectory and preserved lean and skeletal muscle mass, whereas TR did not reproduce these adaptations. Greater gastrocnemius mass with VWR remained evident after adjustment for tumor mass, indicating that reduced tumor burden alone was insufficient to account for muscle preservation. In contrast, adipose tissue wasting, hepatic metabolic remodeling and systemic inflammation remained largely unaffected. TR was also associated with a less favorable body-weight trajectory and greater fat mass loss than in inactive tumor-bearing mice. Exploratory metabolic phenotyping revealed distinct feeding, sleep and resting energy expenditure patterns between the two exercise paradigms. Conclusions VWR selectively preserved skeletal muscle within a persistently altered systemic environment, whereas the TR protocol used here did not reproduce these adaptations. These findings reveal tissue-specific exercise responsiveness during pancreatic cancer cachexia and highlight exercise paradigm characteristics as determinants of tumor-host adaptation.

physiology↗

bioRxiv2026

TBPL2-dependent transcription controls RNA stability and cellular organization in growing oocytes

During oocyte growth, the marked increase in cell size is accompanied by robust RNA polymerase II (Pol II) transcription, generating transcripts that are either translated into proteins or stored as part of the maternal transcriptome. While the RNA decay machinery is known to critically regulate the maternal transcriptome during oocyte maturation, its contribution during the growth phase remains poorly understood. We previously identified an oocyte-specific transcription machinery dependent on the TATA-binding protein paralog TBPL2, which is required for oocyte growth. To investigate how the absence of TBPL2-mediated transcription affects the cellular state of the oocyte, we characterized the phenotypic consequences of the Tbpl2-/- mutation in growing oocytes. Our data reveal that both nuclear and cytoplasmic organizations are profoundly disrupted in the absence of TBPL2-mediated transcription. Given that cytoplasmic organization is closely linked to RNA storage capacity, we examined the expression and localization of proteins involved in mRNA regulation, stability and storage. We observed a marked impairment in the redistribution of these key factors in Tbpl2-/- oocytes. To assess the impact of TBPL2 on RNA storage, we analyzed poly(A) tail length and found a global increase in polyadenylation in mutant oocytes. Gene-specific poly(A) tail analyses revealed differential mRNA changes, with shortened tails for a downregulated transcript and elongated tails for an upregulated one, suggesting stabilization of the latter. Collectively, our findings indicate that TBPL2-mediated transcription is essential for maintaining proper cellular organization in growing oocytes, at least in part by ensuring the functional integrity of the RNA decay machinery.

developmental biology↗

bioRxiv2026

Leveraging Pretrained Vision Transformers for classifying Alcohol Use Disorder using Raw Resting-State EEG

Alcohol Use Disorder (AUD) is a prevalent and debilitating neuropsychiatric condition characterized by compulsive alcohol consumption, impaired control, and negative emotional states, affecting about 28 million adults in the United States. Despite its significant public health burden, there are few objective biomarkers and no reliable neurophysiological tools to assist in its clinical diagnosis. In this study, we investigated the potential of deep learning to classify individuals with AUD using raw resting-state electroencephalogram (EEG) data. EEG recordings were obtained from the Collaborative Study on the Genetics of Alcoholism (COGA), a large, longitudinal, multi-site dataset. The initial cohort included a total of 5,402 recordings from 2,710 participants (aged 12-83, mean age 24; 1,338 males and 1,372 females). To reduce confounding factors, we applied demographic matching, and to address class imbalance, we applied undersampling. Minimal preprocessing was applied to preserve the raw EEG features. We utilized EEGViT, a hybrid deep learning architecture that combines convolutional patch embedding with a Vision Transformer (ViT) pretrained on ImageNet, thereby enabling end-to-end learning directly from raw EEG input. The analysis was stratified by sex and age, and all groups were age-matched. To validate the generalization of the model, models were also trained for Cannabis Use Disorder (CUD) and Opioid Use Disorder (OUD). Results for the AUD model showed a classification accuracy of approximately 56% in the overall dataset, 54% for males, and 58% for females. The CUD model showed an accuracy of about 63% with 59% for females and 69% for males. The OUD model showed an accuracy of about 63% with 61% for females and 65% for males. Temporal analysis indicated that the models performance varied across time intervals, with higher accuracy observed in later minutes compared to earlier ones. While modest, these findings underscore the potential of transformer-based models in psychiatric classification using raw EEG data and provide a foundation for future development of EEG-based diagnostic tools for AUD.

neuroscience↗

bioRxiv2025

Neuroanatomical features reveal accelerated brain age in alcohol use disorder

Background/ObjectivesBrain age is a novel measure to characterize the integrity of neurocognitive functioning and brain health in various psychiatric and neurological disorders. Although there is a literature suggesting premature aging of the brain in individuals with alcohol use disorder (AUD), studies directly examining brain age are rare. Therefore, the current study was designed to estimate brain age in AUD individuals using brain morphological features, such as cortical thickness and brain volume. MethodsThe sample included a group of 30 adult males with a history of AUD but maintaining abstinence and a group of 30 male controls without any history of AUD. Brain age was computed using an XGBoost regression model with 187 brain morphological features of cortical thickness and brain volume as predictors. An exploratory correlational analysis between brain age measures and features of neuropsychological performance, impulsivity, and alcohol consumption was also performed. ResultsFindings revealed that AUD individuals showed an increase of 1.70 years in their brain age relative to their chronological age. Further, in the AUD group, higher brain age was significantly associated with poor executive functioning, while a larger gap between brain age and actual age was associated with lower non-planning impulsivity and later age of onset for regular drinking in those with AUD. ConclusionsAUD individuals manifested accelerated brain aging, possibly representing compromised brain health. Brain age measures were found to be associated with some of the measures of neurocognition, impulsivity, and alcohol consumption. These findings may have important implications for the early identification, prevention, and treatment of AUD. However, future studies with larger sample sizes are needed to confirm these preliminary findings.

neuroscience↗

bioRxiv2024

Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features

Brain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.e., higher family history density (FHD) scores). The AUD dataset included a group of 30 adult males (mean age = 41.25 years) with a lifetime diagnosis of AUD and currently abstinent and a group of 30 male controls (mean age = 27.24 years) without any history of AUD. A second dataset of young adults who were categorized based on their FHD scores comprised a group of 40 individuals (20 males) with high FHD of AUD (mean age = 25.33 years) and a group of 31 individuals (18 males) with low FHD (mean age = 25.47 years). Brain age was predicted using 187 brain morphological features of cortical thickness and brain volume in an XGBoost regression model; a bias-correction procedure was applied to the predicted brain age. Results showed that both AUD and high FHD individuals showed an increase of 1.70 and 0.09 years (1.08 months), respectively, in their brain age relative to their chronological age, suggesting accelerated brain aging in AUD and risk for AUD. Increased brain age was associated with poor performance on neurocognitive tests of executive functioning in both AUD and high FHD individuals, indicating that brain age can also serve as a proxy for cognitive functioning and brain health. These findings on brain aging in these groups may have important implications for the prevention and treatment of AUD and ensuing cognitive decline.

neuroscience↗

bioRxiv2023

RNA polymerase II transcription with partially assembled TFIID complexes

The recognition of core promoter sequences by the general transcription factor TFIID is the first step in the process of RNA polymerase II (Pol II) transcription initiation. Metazoan holo-TFIID is composed of the TATA binding protein (TBP) and of 13 TBP associated factors (TAFs). Inducible Taf7 knock out (KO) results in the formation of a Taf7-less TFIID complex, while Taf10 KO leads to serious defects within the TFIID assembly pathway. Either TAF7 or TAF10 depletions correlate with the detected TAF occupancy changes at promoters, and with the distinct phenotype severities observed in mouse embryonic stem cells or mouse embryos. Surprisingly however, under either Taf7 or Taf10 deletion conditions, TBP is still associated to the chromatin, and no major changes are observed in nascent Pol II transcription. Thus, partially assembled TFIID complexes can sustain Pol II transcription initiation, but cannot replace holo-TFIID over several cell divisions and/or development.

molecular biology↗

bioRxiv2023

Ovariectomy-Induced Arterial Stiffening Differs from Vascular Aging and is Reversed by GPER Activation

Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging, and whether activation of the G protein-coupled estrogen receptor (GPER) could reverse stiffness. Female C57Bl/6J mice were ovariectomized (OVX) at 10 weeks of age or aged to 52 weeks, and some mice were treated with GPER agonists. OVX and aging increased pulse wave velocity to a similar extent independent of changes in blood pressure. Aging increased carotid wall thickness, while OVX increased material stiffness without altering vascular geometry. RNA-Seq analysis revealed that OVX downregulated smooth muscle contractile genes. The enantiomerically pure GPER agonist, LNS8801, reversed stiffness in OVX mice to a greater degree than the racemic agonist G-1. In summary, OVX and aging induced arterial stiffening via potentially different mechanisms. Aging was associated with inward remodeling while OVX induced material stiffness independent of geometry and a loss of the contractile phenotype. This study helps to further our understanding of the impact of menopause on vascular health and identifies LNS8801 as a potential therapy to counteract this detrimental process in women.

pharmacology and toxicology↗

bioRxiv2021

Intermittent brain network reconfigurations and the resistance to social media influence

Since their development, social media has grown as a source of information and has a significant impact on opinion formation. Individuals interact with others and content via social media platforms in a variety of ways but it remains unclear how decision making and associated neural processes are impacted by the online sharing of informational content, from factual to fabricated. Here, we use EEG to estimate dynamic reconfigurations of brain networks and probe the neural changes underlying opinion change (or formation) within individuals interacting with a simulated social media platform. Our findings indicate that the individuals who changed their opinions are characterized by less frequent network reconfigurations while those who did not change their opinions tend to have more flexible brain networks with frequent reconfigurations. The nature of these frequent network configurations suggests a fundamentally different thought process between intervals in which individuals are easily influenced by social media and those in which they are not. We also show that these reconfigurations are distinct to the brain dynamics during an in-person discussion with strangers on the same content. Together, these findings suggest that brain network reconfigurations may not only be diagnostic to the informational context but also the underlying opinion formation. Author SummaryDistinctive neural underpinnings of opinion formation and change during in-person and online social interactions are not well understood. Here, we analyze EEG recordings of the participants interacting with a simulated social media platform and during an in-person discussion using a network-based analysis approach. We show that the structure of network reconfigurations during these interactions is diagnostic of the opinion change and the context in which information was received.

neuroscience↗

bioRxiv2017

Alkyl Gallates Display Elicitor Activities In Tobacco Plants

Alkyl gallates showed elicitor activities on tobacco in both whole plants and cell suspensions. Methyl gallate (MG), ethyl gallate (EG) and n-propyl gallate (PG) infiltration into tobacco leaves induced hypersensitive reaction-like lesions and topical production of autofluorescent compounds revealed under UV light. When sprayed on tobacco plants at 5 mM, EG promoted upregulation of defence-related genes such as the antimicrobial PR1, {beta}-1,3-glucanase PR2, chitinase PR3 and osmotin PR5 target genes. Tobacco BY-2 cells challenged with EG underwent cell death in 48 h, significantly reduced in the presence of the protease inhibitor aprotinin. The three alkyl gallates all caused alkalinisation of the BY-2 extracellular medium, whereas gallic acid did not trigger any pH variation. Using EGTA or LaCl3, we showed that Ca2+ mobilisation occurred in BY-2 cells elicited with EG. Overall, our findings are the first evidence of alkyl gallate elicitor properties with early perception events on plasma membrane, potential hypersensitive reactions and PR-related downstream defence responses in tobacco.\n\nHighlights- Alkyl gallates elicited defence reactions in tobacco\n- Alkyl gallates induced local biochemical changes in tobacco leaves\n- Alkyl gallates caused modification of plasma membrane properties\n- Ethyl gallate led to defence transcript accumulation and dose-dependent cell death associated with hypersensitive response\n- Alkyl gallates are novel elicitor agents well-suited to crop protection schemes.

plant biology↗