Biology subjects

Keating, J.

Publications and source records attributed to Keating, J..

5 recordsLinked to original sources

bioRxiv2026

Oxytocin Modulation of Spinal Circuits Drives Therapeutic Benefits of Massage

Across social species, social touch enhances well-being and reduces pain -- two seemingly distinct benefits that enhance survival. Yet where and how the nervous system integrates these functions, and whether a single mechanism could serve both, remains unknown. Here we show that massage triggers oxytocin release, which shapes both pain and touch reward at the earliest stage of central processing -- the spinal cord -- through a single, state-dependent circuit mechanism. We report that in humans, massage enhances well-being, effects that correlate with endogenous oxytocin release. In mice, gentle touch activates hypothalamic oxytocin neurons that project directly to the spinal dorsal horn. Genetic manipulation of spinal oxytocin circuits alters behavioral responses to both gentle touch and noxious stimuli. Spinal calcium imaging and slice electrophysiology reveal that oxytocin acts on both excitatory and inhibitory spinal neurons to sculpt the relative activity of spinal ascending systems that convey both social touch and pain to the brain. Extending these findings to humans, we show that oxytocin receptors are also expressed on spinal excitatory and inhibitory neurons, and that endogenous oxytocin during massage correlates with altered spinal touch processing. Thus, spinal oxytocin signaling provides an evolutionarily conserved mechanism for the therapeutic benefits of massage.

neuroscience↗

bioRxiv2025

Sensorimotor beta burst dynamics and interhemispheric connectivity in children with developmental coordination disorder

Activity in the beta frequency band appears to play a critical role in sensorimotor processing, with transient bursts exhibiting distinct waveform motifs that may reflect different neural computations. However, how these dynamics relate to motor development and neurodevelopmental conditions remains unclear. Here, we used EEG to investigate sensorimotor beta bursts in children with and without developmental coordination disorder (DCD). We characterized beta bursts during action execution and observation of gross and fine motor actions. Conventional spectral features and overall burst rates did not differ between groups. In contrast, children with DCD showed altered rate modulation of specific burst waveform motifs, including atypical hemispheric lateralization and disrupted interhemispheric connectivity. Critically, motif-specific burst rates were systematically related to motor performance across individuals, with similar relations observed across groups. These findings indicate that waveform-specific beta burst dynamics track graded variation in motor performance, rather than mapping selectively onto diagnostic status. Beta burst variability may therefore reflect the functional expression of motor performance, rather than a disorder-specific neural mechanism underlying DCD. This work highlights the importance of beta burst waveform diversity for understanding variability in sensorimotor function across development.

neuroscience↗

bioRxiv2020

ACIS, A Novel KepTide™, Binds to ACE-2 Receptor and Inhibits the Infection of SARS-CoV2 Virus in vitro in Primate Kidney Cells: Therapeutic Implications for COVID-19

Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) caused by a virus known as SARS-Coronavirus 2 (SARS-CoV2). Without a targeted-medicine, this disease has been causing a massive humanitarian crisis not only in terms of mortality, but also imposing a lasting damage to social life and economic progress of humankind. Therefore, an immediate therapeutic strategy needs to be intervened to mitigate this global crisis. Here, we report a novel KepTide (Knock-End Peptide) therapy that nullifies SARS-CoV2 infection. SARS-CoV2 employs its surface glycoprotein "spike" (S-glycoprotein) to interact with angiotensin converting enzyme-2 (ACE-2) receptor for its infection in host cells. Based on our in-silico-based homology modeling study validated with a recent X-ray crystallographic structure (PDB ID:6M0J), we have identified that a conserved motif of S-glycoprotein that intimately engages multiple hydrogen-bond (H-bond) interactions with ACE-2 enzyme. Accordingly, we designed a peptide, termed as ACIS (ACE-2 Inhibitory motif of Spike), that displayed significant affinity towards ACE-2 enzyme as confirmed by biochemical assays such as BLItz and fluorescence polarization assays. Interestingly, more than one biochemical modifications were adopted in ACIS in order to enhance the inhibitory action of ACIS and hence called as KEpTide. Consequently, a monolayer invasion assay, plaque assay and dual immunofluorescence analysis further revealed that KEpTide efficiently mitigated the infection of SARS-CoV2 in vitro in VERO E6 cells. Finally, evaluating the relative abundance of ACIS in lungs and the potential side-effects in vivo in mice, our current study discovers a novel KepTide therapy that is safe, stable, and robust to attenuate the infection of SARS-CoV2 virus if administered intranasally.

biochemistry↗

bioRxiv2020

Lymph Node Morphology in Stage II Colorectal Cancer

BackgroundColorectal cancer is one of the leading causes of cancer-associated morbidity and mortality worldwide. The local anti-tumour immune response is particularly important for patients with stage II where the tumour-draining lymph nodes have not yet succumbed to tumour spread. The lymph nodes allow for the expansion and release of B cell compartments such as primary follicles and germinal centres. A variation in this anti-tumour immune response may influence the observed clinical heterogeneity in stage II patients. AimThe aim of this study was to explore tumour-draining lymph node histomorphological changes and tumour pathological risk factors including the immunomodulatory microRNA-21 (miR-21) in a small cohort of stage II CRC. MethodsA total of 23 stage II colorectal cancer patients were included. Tumour and normal mucosa samples were analysed for miR-21 expression levels and B-cell compartments were quantified from Haematoxylin and Eosin slides of lymph nodes. These measures were compared to clinicopathological risk factors such as perforation, bowel obstruction, T4 stage and high-grade. ResultsWe observed greater follicle density in patients with a lower tumour T stage and higher germinal centre density in patients with higher pre-operative carcinoembryonic antigen levels. Trends were also detected between tumours with deficiency in mismatch repair proteins, lymphatic invasion and both the density and size of B-cell compartments. Lastly, elevated tumour miR-21 was associated with decreased follicle and germinal centre size. ConclusionVariation in B-cell compartments of tumour-draining lymph nodes is associated with clinicopathological risk factors in stage II CRC patients. What does this paper add to the literature?This study demonstrates the variability of tumour draining lymph node morphological features in stage II CRC patients. This provides new scope for biomarker discovery in stage II CRC patients which is a research priority for this patient group.

cancer biology↗

bioRxiv2018

Crowdsourced study of children with autism and their typically developing siblings identifies differences in taxonomic and predicted function for stool-associated microbes using exact sequence variant analysis.

BackgroundThe existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations efforts to identify microbial biomarkers have been limited due to problems stratifying participants within the broad phenotype of ASD and a lack of appropriately matched controls. To overcome these limitations and investigate the relationship between ASD and the gut microbiome, we ran a crowdsourced study of families 2-7 year old sibling pairs, where one child of the pair had a diagnosis of ASD and the other child did not.\n\nMethodsParents of age-matched sibling pairs electronically consented and completed study procedures via a secure web portal (microbiome.stanford.edu). Parents collected stool samples from each child, responded to behavioral questionnaires about the ASD childs typical behavior, and whenever possible provided a home video of their ASD childs natural social behavior. We performed DNA extraction and 16S rRNA amplicon sequencing on 117 stool samples (60 ASD and 57 NT) that met all study design eligibility criteria. Using DADA2, Exact Sequence Variants (ESVs) were identified as taxonomic units, and three statistical tests were performed on ESV abundance counts: (1) permutation test to determine differences between sibling pairs, (2) differential abundance test using a zero-inflated gaussian mixture model to account for the sparse abundance matrix, and (3) differential abundance test after modeling under a negative binomial distribution. The potential functional gene abundance for each sample was also inferred from the 16S rRNA data, providing KEGG Ortholog (KO), which were analyzed for differential abundance.\n\nResultsIn total, 21 ESVs had significantly differentially proportions in stool of children with ASD and their neurotypical siblings. Of these 21 ESVs, 11 were enriched in neurotypical children and ten were enriched in children with ASD. ESVs enriched in the ASD cohort were predominantly associated with Ruminococcaceae and Bacteroidaceae; while those enriched in controls were more diverse including taxa associated with Bifidobacterium, Porphyromonas, Slackia, Desulfovibrio, Acinetobacter johnsonii, and Lachnospiraceae. Exact Variant Analysis suggested that Lachnospiraceae was specific to the control cohort, while Ruminococcaceae, Tissierellaceae and Bacteroidaceae were significantly enriched in children with ASD. Metabolic gene predictions determined that while both cohorts harbor the butyrogenic pathway, the ASD cohort was more likely to use the 4-aminobutanoate (4Ab) pathway, while the control cohort was more likely to use the pyruvate pathway. The 4Ab pathway releases harmful by-products like ammonia and can shunt glutamate, affecting its availability as an excitatory neurotransmitter. Finally, we observed differences in the carbohydrate uptake capabilities of various ESVs identified between the two cohorts.

microbiology↗