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Morris, P. J.

Publications and source records attributed to Morris, P. J..

2 recordsLinked to original sources

Population fragmentation leads to morpho-functional variation in British red squirrels (Sciurus vulgaris)

It is well-known that population fragmentation and isolation can lead to rapid morphological and functional divergence, with the effect being particularly well-documented in rodents. Here, we investigated whether such a phenomenon could be identified in the Eurasian red squirrel (Sciurus vulgaris), which was once widespread across the majority of Great Britain, but suffered a severe population decline across the 20th century, leaving a highly fragmented distribution. The aim was to test for morphological and biomechanical variation of the mandible between the remaining British red squirrel populations. Linear and geometric morphometric methods were used to analyse shape in a sample of over 250 squirrel mandibles from across the UK and Germany. Canonical variates analysis identified significant shape differences between most British red squirrel populations, but particularly between squirrels from Formby and those from other populations. Linear measurements showed that Formby red squirrels have a significantly lower mechanical advantage of the temporalis muscle, indicating that they are less efficient at gnawing. We suggest that this difference may be related to past supplemental feeding of Formby squirrels with peanuts, which are less mechanically resistant than food items that occur naturally in the diet of British red squirrels.

evolutionary biology↗

Targeting neuronal activity-regulated neuroligin-3 dependency for high-grade glioma therapy

Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. We demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma, diffuse intrinsic pontine glioma and adult glioblastoma fail to grow in Nlgn3 knockout mice. Glioma exposure to Nlgn3 results in numerous signaling consequences, including early focal adhesion kinase activation upstream of PI3K-mTOR. Nlgn3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. Administration of ADAM10 inhibitors robustly blocks HGG xenograft growth. This work defines the therapeutic potential of and a promising strategy for targeting Nlgn3 secretion in the glioma microenvironment, which could prove transformative for treatment of HGG.

neuroscience↗