Biology subjects

Kenny, P.

Publications and source records attributed to Kenny, P..

3 recordsLinked to original sources

bioRxiv2026

Sedimentary ancient DNA reveals Late Pleistocene faunal connectivity between Ireland and Eurasia

Late Pleistocene sea-level fluctuations and glacial corridors intermittently connected the island of Ireland to Britain and continental Eurasia, shaping patterns of megafaunal dispersal and occupation. However, the scarcity of genetic data from ancient Irish fauna has limited our understanding of their demographic histories and relationships to continental populations. To address this, we generated sedimentary ancient DNA sequences from Castlepook Cave in southwest Ireland, detecting twelve ancient taxa, including two without zooarchaeological records at the site. We recovered the first mitochondrial sequences from Irish cave hyenas and woolly mammoths, providing new insights into their maternal population history: cave hyenas carried mtDNA haplogroup A1, previously identified in Late Pleistocene European populations, while woolly mammoths belonged to clade III/B2, which was replaced in Europe at approximately the same time. We also identify two mitochondrial clades (1b and 2), consistent with pre-Last Glacial Maximum mitochondrial lineage turnover in Ireland. Together, these results indicate that Irish megafauna formed a biogeographical continuum with their conspecifics in Europe, extend the known geographical range of several mtDNA lineages, and support faunal connectivity at the northwestern edge of Europe prior to the Last Glacial Maximum.

evolutionary biology↗

bioRxiv2021

Melanomagenesis driven by a kinase-dead mutant BRAF lacking codons 600-618

While considerable success has been achieved with treating BRAF-V600E mutant tumors in several organ systems, tumors expressing non-V600E BRAF mutations remain a significant clinical challenge. Such atypical BRAF mutations are classified based on their kinase activity, RAS-dependence and their requirement for dimerization to function. We identified an unusually large in-frame deletion in a melanoma patient, encompassing codons 600-618 in the kinase domain. This patient experienced rapid disease progression when treated with dual BRAF/MEK inhibition. To determine whether and how such a large in-frame BRAF deletion might be activating, we ectopically expressed it in HEK293 cells and monitored BRAF pathway activation and response to BRAF and MEK inhibitors. We demonstrate that this mutation results in a kinase-deficient BRAF mutant which, nevertheless, activates MEK/ERK signaling in a dimerization-dependent manner, placing this mutation among the class III BRAF mutants.

cancer biology↗

bioRxiv2020

Prelimbic-amygdala overexcitability mediates trait vulnerability in a novel mouse model of acute social defeat stress

BACKGROUNDDepression is a debilitating neuropsychiatric disorder with 20% lifetime prevalence in the developed world but only approximately half of afflicted individuals respond to currently available therapies. While there is growing understanding of the neurobiological underpinnings of the depressed brain, much less is known about the preexisting circuitry leading to selective vulnerability versus resilience. Elucidating these networks could lead to novel preventative approaches. METHODSWe developed a model of acute social defeat stress (ASDS) that allows classification of male mice into "susceptible" (socially avoidant) versus "resilient" (expressing control-level social approach) one hour after exposure to six minutes of social stress. Using circuit tracing and high-resolution confocal imaging, we explored differences in activation and dendritic spine density and morphology in the prelimbic to basolateral amygdala (PL[->]BLA) circuit in resilient versus susceptible mice. To test the functional relevance of identified structure/function differences to divergent behavioral responses, we used an intersectional chemogenetic approach to inhibit the PL[->]BLA circuit during or prior to ASDS. RESULTSSusceptible mice had greater PL[->]BLA recruitment during ASDS and activated PL[->]BLA neurons from susceptible mice had more and larger mushroom spines compared to resilient mice. Inhibition of the PL[->]BLA circuit led to a population shift towards resilience. CONCLUSIONPreexisting PL[->]BLA structure/function differences mediate divergent behavioral responses to ASDS in male mice. These results support the PL[->]BLA circuit as a biomarker of trait vulnerability and potential target for prevention of stress-induced psychopathology.

neuroscience↗