Biology subjects

Farmer, S.

Publications and source records attributed to Farmer, S..

9 recordsLinked to original sources

bioRxiv2025

Wearable MEG data recorded during human stepping

Non-invasive spatiotemporal imaging of brain activity during large-scale, whole body movement is a significant methodological challenge for the field of movement neuroscience. Here, we present a dataset recorded using a new imaging modality - optically-pumped magnetoencephalography (OP-MEG) - to record brain activity during human stepping. Participants (n=3) performed a visually guided stepping task requiring precise foot placement while dual-axis and triaxial OP-MEG and leg muscle activity (electromyography, EMG) were recorded. The dataset also includes a structural MRI for each participant and foot kinematics. We validate the fidelity of the OPM data by showing movement-related beta band desynchronization source localised to the primary motor cortex. This multimodal dataset offers a resource for methodological development and testing for OPM data (e.g., movement-related interference rejection), within-subject analyses, and exploratory analyses to generate hypotheses for further work on the neural control of human stepping.

neuroscience↗

bioRxiv2024

A three-country analysis of the gut microbiome indicates taxon associations with diet vary by location and strain

Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. While significant efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research lacks representation from low- and middle-income countries such as Mexico. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,291 individuals across three countries, we examine two bacterial genera prevalent in the human gut, Prevotella and Faecalibacterium, which have gained significant attention due to their potential roles in human health. We find that they show significant associations with many aspects of diet, but that these associations vary in scale and direction, depending on the level of metagenomic resolution and the contextual population. These results highlight the growing importance of assembling metagenomic datasets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.

microbiology↗

bioRxiv2024

Large-Scale Motor Dynamics Associated with Reaching are Altered in Essential Tremor

Essential Tremor (ET) is a very common neurological disorder characterised by involuntary rhythmic movements attributable to pathological synchronization within corticothalamic circuits. Previous work has focused on tremor in isolation, overlooking broader disturbances to motor control during naturalistic movements such as reaching. We hypothesised that ET disrupts the sequential engagement of large-scale rhythmic brain networks, leading to both tremor and deficits in motor planning and execution. To test this, we performed whole-head neuroimaging during an upper-limb reaching task using high-density electroencephalography in ET patients and healthy controls, alongside optically pumped magnetoencephalography in a smaller cohort. Key motor regions--including the supplementary motor area, premotor cortex, posterior parietal cortex, and motor cerebellum--were synchronized to tremor rhythms. Patients exhibited a 15% increase in low beta (14-21 Hz) desynchronization over the supplementary motor area during movement, which strongly correlating with tremor severity (R2 = 0.85). A novel dimensionality reduction technique revealed four distinct networks accounting for 97% of the variance in motor-related brain-wide oscillations, with ET altering their sequential engagement. Consistent with our hypothesis, the frontoparietal beta network- normally involved in motor planning-exhibited additional desynchronization during movement execution in ET patients. This altered engagement correlated with slower movement velocities, suggesting an adaptation towards feedback-driven motor control. These findings reveal fundamental disruptions in distributed motor control networks in ET and identify novel biomarkers as targets for next-generation brain stimulation therapies.

neuroscience↗

bioRxiv2022

Effects of Variation in Urine Sample Storage Conditions on 16S Urogenital Microbiome Analyses

Replicability is a well-established challenge in microbiome research with a variety of contributing factors at all stages, from sample collection to code execution. Here, we focus on voided urine sample storage conditions for urogenital microbiome analysis. Using urine samples collected from 10 healthy adult women, we investigated the microbiome preservation efficacy of AssayAssure(R) Genelock (as opposed to no preservative) under different temperature conditions. We varied temperature over 48 hours in order to examine the impact of conditions samples may experience with home voided urine collection and shipping to a central biorepository. The following common lab and shipping conditions were investigated: -20C, ambient temperature, 4C, a freeze-thaw cycle, and a heat cycle. At 48 hours, all samples were stored at -80C until processing. After generating 16S rRNA gene amplicon sequencing data using the highly sensitive KatharoSeq protocol, we observed individual variation in both alpha and beta diversity metrics below interhuman differences, corroborating reports of individual microbiome variability in other specimen types. While there was no significant difference in beta diversity when comparing AssayAssure(R) Genelock vs. no preservative, we did observe a higher concordance with AssayAssure samples shipped at colder temperatures (-20C and 4C) when compared to the samples shipped at -20C without preservative. Our results indicate that AssayAssure does not introduce a significant amount of microbial bias when used on a range of temperatures but is most effective at colder temperatures. ImportanceThe urogenital microbiome is an understudied yet important human microbiome niche. Research has been stimulated by the relatively recent discovery that urine is not sterile: urinary tract microbes have been linked to health problems including urinary infections, incontinence, and cancer. The quality of life and economic impact of UTIs and urgency incontinence alone are enormous, with $3.5 billion and $82.6 billion respectively spent in the U.S. annually. Given the low biomass of urine, novelty of the field, and well-established replicability bias in microbiome studies, it is critical to study storage conditions on urine samples to minimize microbial biases. Efficient and reliable preservation methods permit home self-sample collection and shipping, increasing the accessibility of larger-scale studies. Here, we examined both buffer and temperature variation effects on 16S rRNA gene amplicon sequencing results from urogenital samples, providing data on the consequences of common storage methods on urogenital microbiome results.

microbiology↗

bioRxiv2022

VMHdm/cSF-1 Neuronal Circuits Regulate Skeletal Muscle PGC1-α via the Sympathoadrenal Drive

ObjectiveTo adapt to metabolically challenging environments, the central nervous system (CNS) orchestrates metabolism of peripheral organs including skeletal muscle. The organ-communication between the CNS and skeletal muscle has been investigated, yet our understanding of the neuronal pathway from the CNS to skeletal muscle is still limited. Neurons in the dorsomedial and central parts of the ventromedial hypothalamic nucleus (VMHdm/c) expressing steroidogenic factor-1 (VMHdm/cSF-1 neurons) are key for metabolic adaptations to exercise, including increased basal metabolic rate and skeletal muscle mass in mice. However, the mechanisms by which VMHdm/cSF-1 neurons regulate skeletal muscle function remain unclear. Here, we show that VMHdm/cSF-1 neurons increase the sympathoadrenal activity and regulate skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1) in mice via multiple downstream nodes. MethodsOptogenetics was used to specifically manipulate VMHdm/cSF-1 neurons combined with genetically-engineered mice and surgical manipulation of the sympathoadrenal activity. ResultsOptogenetic activation of VMHdm/cSF-1 neurons dramatically elevates mRNA levels of skeletal muscle Pgc-1, which regulates a spectrum of skeletal muscle function including protein synthesis and metabolism. Mechanistically, the sympathoadrenal drive coupled with {beta}2 adrenergic receptor ({beta}2AdR) is essential for VMHdm/cSF-1 neurons-mediated increases in skeletal muscle PGC1-. Specifically, both adrenalectomy and {beta}2AdR knockout block augmented skeletal muscle PGC1- by VMHdm/cSF-1 neuronal activation. Optogenetic functional mapping reveals that downstream nodes of VMHdm/cSF-1 neurons are functionally redundant to increase circulating epinephrine and skeletal muscle PGC1-. ConclusionsCollectively, we propose that VMHdm/cSF-1 neurons-skeletal muscle pathway, VMHdm/cSF-1 neurons[->]multiple downstream nodes[->]the adrenal gland[->]skeletal muscle {beta}2AdR, underlies augmented skeletal muscle function for metabolic adaptations.

neuroscience↗

bioRxiv2022

Bacterial metatranscriptomes in wastewater can differentiate virally infected human populations

Monitoring wastewater samples at building-level resolution screens large populations for SARS-CoV-2, prioritizing testing and isolation efforts. Here we perform untargeted metatranscriptomics on virally-enriched wastewater samples from 10 locations on the UC San Diego campus, demonstrating that resulting bacterial taxonomic and functional profiles discriminate SARS-CoV-2 status even without direct detection of viral transcripts. Our proof-of-principle reveals emergent threats through changes in the human microbiome, suggesting new approaches for untargeted wastewater-based epidemiology.

microbiology↗

bioRxiv2019

Triphenyl phosphate is a selective PPARγ modulator that does not induce brite adipogenesis in vitro and in vivo

Triphenyl phosphate (TPhP) is an environmental PPAR{gamma} ligand, and growing evidence suggests that it is a metabolic disruptor. We have shown previously that the structurally similar ligand, tributyltin, does not induce brite adipocyte gene expression. Here, using in vivo and in vitro models, we tested the hypothesis that TPhP is a selective PPAR{gamma} ligand, which fails to induce brite adipogenesis. C57BL/6J male mice were fed either a low or very high fat diet for 13 weeks. From weeks 7-13, mice were injected intraperitoneally, daily, with vehicle, rosiglitazone (Rosi), or TPhP (10 mg/kg). Compared to Rosi, TPhP did not induce expression of browning-related genes (e.g. Elovl3, Cidea, Acaa2, CoxIV) in mature adipocytes isolated from inguinal adipose. To determine if this resulted from an effect directly on the adipocytes, 3T3-L1 cells and primary human preadipocytes were differentiated into adipocytes in the presence of Rosi or TPhP. Rosi, but not TPhP, induced expression of brite adipocyte genes, mitochondrial biogenesis and cellular respiration. Further, Rosi and TPhP induced distinct proteomes and phosphoproteomes; Rosi enriched more regulatory pathways related to fatty acid oxidation and mitochondrial proteins. We assessed the role of phosphorylation of PPAR{gamma} in these differences in 3T3-L1 cells. Only Rosi protected PPAR{gamma} from phosphorylation at Ser273. TPhP gained the ability to stimulate brite adipocyte gene expression in the presence of the CDK5 inhibitor and in 3T3-L1 cells expressing alanine at position 273. We conclude that TPhP is a selective PPAR{gamma} modulator that fails to protect PPAR{gamma} from phosphorylation at ser273.

pharmacology and toxicology↗

bioRxiv2018

Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival During Cancer Cachexia Syndrome

Cancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that Toll-like receptor 4 (TLR4) mediates AT remodeling, in particular, AT browning and inflammatory response in mice bearing Lewis lung carcinoma (LLC). LLC tumor-bearing (TB) TLR4-/- mice were spared from AT remodeling due to a reduced macrophage infiltration and adipocyte atrophy. TLR4-/- mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 reproduced the main protective effect against AT remodeling found in TLR4-/- TB mice. Moreover, the treatment was effective in prolonging the survival and attenuating tumor mass growth when compared to non-treated-TB animals. Further, tumor-induced elevation of circulating pro-inflammatory cytokines was similarly abolished in both genetic ablation and pharmacological inhibition of TLR4. These data suggest that TLR4 is a critical mediator and a promising therapeutic target for cancer-induced AT remodeling.\n\nHIGHLIGHTSO_LIGenetic ablation and pharmacological inhibition of TLR4 attenuate adipose tissue remodeling during cancer-associated cachexia;\nC_LIO_LITLR4 suppression play an essential role in the browning phenotype induced by cachexia;\nC_LIO_LIAdministration of TLR4 drug inhibitor increase survival and reduces tumor mass growth in tumor bearing mice;\nC_LIO_LITLR4 pathway is a promising target for cancer-cachexia therapeutic intervention.\nC_LI

cancer biology↗

bioRxiv2018

Temporal ordering of input modulates connectivity formation in a developmental neuronal network model of the cortex

Preterm infant brain activity is discontinuous; bursts of activity recorded using EEG (electroencephalography), thought to be driven by subcortical regions, display scale free properties and exhibit a complex temporal ordering known as long-range temporal correlations (LRTCs). During brain development, activity-dependent mechanisms are essential for synaptic connectivity formation, and abolishing burst activity in animal models leads to weak disorganised synaptic connectivity. Moreover, synaptic pruning shares similar mechanisms to spike-timing dependent plasticity (STDP), suggesting that the timing of activity may play a critical role in connectivity formation. We investigated, in a computational model of leaky integrate-and-fire neurones, whether the temporal ordering of burst activity within an external driving input could modulate connectivity formation in the network. Connectivity evolved across the course of simulations using an approach analogous to STDP, from networks with initial random connectivity. Small-world connectivity and hub neurones emerged in the network structure - characteristic properties of mature brain networks. Notably, driving the network with an external input which exhibited LRTCs in the temporal ordering of burst activity facilitated the emergence of these network properties, increasing the speed with which they emerged compared with when the network was driven by the same input with the bursts randomly ordered in time. Moreover, the emergence of small-world properties was dependent on the strength of the LRTCs. These results suggest that the temporal ordering of burst activity could play an important role in synaptic connectivity formation and the emergence of small-world topology in the developing brain.

neuroscience↗