Biology subjects

George, T.

Publications and source records attributed to George, T..

6 recordsLinked to original sources

bioRxiv2025

Mapping brain function underlying naturalistic motor observation and imitation using high-density diffuse optical tomography

BackgroundAutism spectrum disorder (ASD), a condition defined by deficits in social communication, restricted interests, and repetitive behaviors, is associated with early impairments in motor imitation that persist through childhood and into adulthood. Alterations in the mirror neuron system (MNS), crucial for interpreting and imitating actions, may underlie these ASD-associated differences in motor imitation. High-density diffuse optical tomography (HD-DOT) overcomes logistical challenges of functional magnetic resonance imaging to enable identification of neural substrates of naturalistic motor imitation. ObjectiveWe aim to investigate brain function underlying motor observation and imitation in autistic and non-autistic adults. We hypothesize that HD-DOT will reveal greater activation in regions associated with the MNS during motor imitation than motor observation, and that MNS activity will negatively correlate with autistic traits and motor fidelity. MethodsWe imaged brain function using HD-DOT in N = 100 participants as they engaged in observing or imitating a sequence of arm movements. Additionally, during imitation, participant movements were simultaneously recorded with 3D cameras for computer-vision-based assessment of motor imitation (CAMI). Cortical responses were estimated using general linear models, and multiple regression was used to test for associations with autistic traits, assessed via the Social Responsiveness Scale-2 (SRS), and imitation fidelity, assessed via CAMI. ResultsBoth observing and imitating motor movements elicited significant activations in higher-order visual and MNS regions, including the inferior parietal lobule, superior temporal gyrus, and inferior frontal gyrus. Imitation additionally exhibited greater activation in the superior parietal lobule, primary motor cortex, and supplementary motor area. Notably, the right temporal-parietal junction exhibited activation during observation but not during imitation. Higher autistic traits were associated with increased activation during motor observation in the right superior parietal lobule. No significant correlation between brain activation and CAMI scores was observed. ConclusionsOur findings provide robust evidence of shared and task-specific cortical responses underlying motor observation and imitation, emphasizing the differential engagement of MNS regions during motor observation and imitation.

neuroscience↗

bioRxiv2024

Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism

Carbohydrate Response Element-Binding Protein (ChREBP) is a transcription factor that activates key genes involved in glucose, fructose, and lipid metabolism in response to carbohydrate feeding, but its other potential roles in metabolic homeostasis have not been as well studied. We used liver-selective GalNAc-siRNA technology to suppress expression of ChREBP in rats fed a high fat/high sucrose diet and characterized hepatic and systemic responses by integrating transcriptomic and metabolomic analyses. GalNAc-siChREBP-treated rats had lower levels of multiple short-chain acyl CoA metabolites compared to rats treated with GalNAc-siCtrl containing a non-targeting siRNA sequence. These changes were related to a sharp decrease in free CoA levels in GalNAc-siChREBP treated-rats, accompanied by lower expression of transcripts encoding enzymes and transporters involved in CoA biosynthesis. These activities of ChREBP likely contribute to its complex effects on hepatic lipid and energy metabolism. While core enzymes of fatty acid (FA) oxidation are induced by ChREBP knockdown, accumulation of liver acylcarnitines and circulating ketones indicate diversion of acetyl CoA to ketone production rather than complete oxidation in the TCA cycle. Despite strong suppression of pyruvate kinase and activation of pyruvate dehydrogenase, pyruvate levels were maintained, likely via increased expression of pyruvate transporters, and decreased expression of lactate dehydrogenase and alanine transaminase. GalNAc-siChREBP treatment increased hepatic citrate and isocitrate levels while decreasing levels of distal TCA cycle intermediates. The drop in free CoA levels, needed for the 2-ketoglutarate dehydrogenase reaction, as well as a decrease in transcripts encoding the anaplerotic enzymes pyruvate carboxylase, glutamate dehydrogenase, and aspartate transaminase likely contributed to these effects. GalNAc-siChREBP treatment caused striking increases in PRPP and ZMP/AICAR levels, and decreases in GMP, IMP, AMP, NaNM, NAD(P), and NAD(P)H levels, accompanied by reduced expression of enzymes that catalyze late steps in purine and NAD synthesis. ChREBP suppression also increased expression of a set of plasma membrane amino acid transporters, possibly as an attempt to replenish TCA cycle intermediates. In sum, combining transcriptomic and metabolomic analyses has revealed regulatory functions of ChREBP that go well beyond its canonical roles in control of carbohydrate and lipid metabolism to now include mitochondrial metabolism and cellular energy balance.

physiology↗

bioRxiv2024

Replay of procedural experience is independent of the hippocampus

Sleep is critical for consolidating all forms of memory1-3, from episodic experience to the development of motor skills4-6. A core feature of the consolidation process is offline replay of neuronal firing patterns that occur during experience7,8. This replay is thought to originate in the hippocampus and trigger the reactivation of ensembles of cortical and subcortical neurons1,3,9-18. However, non-declarative memories do not require the hippocampus for learning or for sleep-dependent consolidation19-26 meaning what drives their consolidation is unknown. Here we show, using an unsupervised method, that replay occurs in the dorsal striatum of mice during offline consolidation of a non-declarative, procedural, memory and that this replay is generated independently of the hippocampus. Replay occurred at both real-world and time-compressed speeds and was also prioritised both at the level of the individual neurons and the type of neural sequence. Complete bilateral lesions of the hippocampus had no effect on any feature of this replay. Our results demonstrate that procedural replay during consolidation of a non-declarative memory is independent of the hippocampus. These results support the view that replay drives active consolidation of all types of memory during sleep but challenges the idea that the hippocampus is the source of this replay.

neuroscience↗

bioRxiv2022

Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

Precision medicine is critically dependent on better methods for diagnosing and staging disease and predicting drug response. Histopathology using Hematoxylin and Eosin (H&E) stained tissue - not genomics - remains the primary diagnostic method in cancer. Recently developed highly-multiplexed tissue imaging methods promise to enhance research studies and clinical practice with precise, spatially-resolved, single-cell data. Here we describe the "Orion" platform for collecting and analyzing H&E and high-plex immunofluorescence (IF) images from the same cells in a whole-slide format suitable for diagnosis. Using a retrospective cohort of 74 colorectal cancer resections, we show that IF and H&E images provide human experts and machine learning algorithms with complementary information that can be used to generate interpretable, multiplexed image-based models predictive of progression-free survival. Combining models of immune infiltration and tumor-intrinsic features achieves a hazard ratio of [~]0.05, demonstrating the ability of multi-modal Orion imaging to generate high-performance biomarkers.

cancer biology↗

bioRxiv2018

Genome wide association study of body weight, body mass index, adiposity, and fasting glucose in 3,173 outbred rats

Objective Obesity is influenced by genetic and environmental factors. Despite success of human genome wide association studies (GWAS), the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify genetic loci underlying obesity and related morphometric and metabolic traits.Methods We measured obesity-relevant traits including body weight, body length, body mass index, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat GWAS to date. Genetic loci were identified using a linear mixed model that accounted for the complex family relationships of the HS and covariate to account for differences among the three phenotyping centers.Results We identified 32 independent loci, several of which contained only a single gene (e.g. Epha5, Nrg1 and Klhl14) or obvious candidate genes (Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and extensive pleiotropy at individual loci.Conclusions These studies demonstrate utility of HS rats for investigating the genetics of obesity related traits across institutions and identify several candidate genes for future functional testing.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genetics↗

bioRxiv2018

Ameliorative potential of curcumin on cigarette smoke extract induced cognitive impairment in zebrafish

Curcumin is a major phyto-constituent of Curcuma longa. It has been reported that it that it showed various pharmacological actions via anti-oxidant, anti-inflammatory, and immunomodulatory actions. The present study undergoes the therapeutic evaluation of curcumin in cigarette smoke extract (CSE) exposure induced cognitive impairment in zebrafish. Methods: The cognitive impairment was induced by exposure to 25 ml of 200 % CSE; 10 minutes/day, for 7 consecutive days. The pre-treatment of curcumin (10 and 20 mg/kg) and montelukast(20 mg/kg) were exposed in 25 ml drug solution (10 minutes/day for 10 consecutive days). The changes of CSE induced cognitive dysfunction were evaluated by using different test methods such as colour recognition test; partition preference test; horizontal compartment test; and T-Maze tests. Further, the CSE exposure induced changes of biochemical parameters i.e., acetylcholinesterase activity; lipid peroxidation; reduced glutathione; and total protein levels were estimated in the brain of zebrafish. The pre-exposure of curcumin shown to produce the ameliorative effect against CSE induced neurocognitive impairments along with alteration of biochemical changes. Theseresults were comparable to reference control i.e., montelukast pre-treated group. Therefore, the curcumin can be served as newer medicines for immunological reaction associated neurocognitive disorders like Alzheimer and multiple sclerosis due to its potential anti-oxidative; anti-inflammatory; immunomodulatory; and acetylcholinesterase inhibitory actions.\n\nSUMMARYLoss of memory is a major problem in old age population. Curcumin used to treats the various neurological disorders. Curcumin possess the ameliorative potential in toxin induced neurocognitive function.

animal behavior and cognition↗