Biology subjects

McNally, J.

Publications and source records attributed to McNally, J..

4 recordsLinked to original sources

bioRxiv2026

A critical role for the murine anterior insula in male social avoidance after early life maltreatment.

Maltreatment in children and adolescents poses a major public health crisis as a primary factor for the development of adult psychiatric disorders. However effective treatments for symptoms resulting from early life maltreatment are lacking, in part due to a lack of understanding of how neural circuits are disrupted in adulthood after childhood and adolescent abuse. We used a novel model of developmental maltreatment (early adolescent chronic social defeat stress, eaCSDS) in C57/B6J mice to examine behavioral and circuit-level effects in the adult anterior insula (AI). We combined chemogenetics, whole brain c-fos imaging and multi-site LFP to investigate the role of the AI and related circuitry in adult behavioral dysfunction after early life maltreatment. Behavioral analysis in adult animals reveals that males, but not females, show robust generalized social avoidance after social defeat in early adolescence. Chemogenetic silencing of AI neurons in males, but not females, reduces social avoidance in adulthood after eaCSDS. In males, whole brain c-fos imaging and multi-site LFP recordings further reveal circuit-level disruptions in connectivity to AI, implicating AI dysregulation as a driver of adult male social avoidance after adolescent maltreatment. Together these findings reveal AI as a novel circuits-level target whose activity normalization may reduce fear-based symptoms of adolescent maltreatment in adulthood specifically in males.

neuroscience↗

bioRxiv2024

Turgor pressure affects transverse stiffness and resonant frequencies of buzz-pollinated poricidal anther

Several agriculturally valuable plants store their pollen in tube-like poricidal anthers, which release pollen through buzz pollination. In this process, bees rapidly vibrate the anther using their indirect flight muscles. The stiffness and resonant frequency of the anther are crucial for effective pollen release, yet the impact of turgor pressure on these properties is not well understood. Here, we perform three-point flexure tests and experimental modal analysis to determine anther transverse stiffness and resonant frequency, respectively. Dynamic nanoindentation is used to identify the anthers storage modulus as a function of excitation frequency. We subsequently develop mathematical models to estimate how turgor pressure changes after the anther is removed from a flower, thereby emulating zero water availability. We find that 30 minutes post-ablation, anther stiffness decreases 60%. Anther resonant frequency decreases 20% 60 minutes post-ablation. Models indicate turgor pressure in the fresh anther is about 0.2 - 0.3 MPa. Our findings suggest that natural fluctuations in turgor pressure due to environmental factors like temperature and light intensity may require bees to adjust their foraging behaviors. Interestingly, anther storage modulus increased with excitation frequency, underscoring the need for more sophisticated mechanical models that consider viscous fluid transport through plant tissue moving forward.

biophysics↗

bioRxiv2022

3D-surface reconstruction of cellular cryo-soft X-ray microscopy tomograms using semi-supervised deep learning

Cryo-soft X-ray tomography (cryo-SXT) is a powerful method to investigate the ultrastructure of cells, offering resolution in the tens of nm range and strong contrast for membranous structures without requirement for labeling or chemical fixation. The short acquisition time and the relatively large volumes acquired allow for fast acquisition of large amounts of tomographic image data. Segmentation of these data into accessible features is a necessary step in gaining biologically relevant information from cryo-soft X-ray tomograms. However, manual image segmentation still requires several orders of magnitude more time than data acquisition. To address this challenge, we have here developed an end-to-end automated 3D-segmentation pipeline based on semi-supervised deep learning. Our approach is suitable for high-throughput analysis of large amounts of tomographic data, while being robust when faced with limited manual annotations and variations in the tomographic conditions. We validate our approach by extracting three-dimensional information on cellular ultrastructure and by quantifying nanoscopic morphological parameters of filopodia in mammalian cells.

bioinformatics↗

bioRxiv2018

Analysis of cholesterol export from endo-lysosomes by Niemann Pick C2 protein using combined fluorescence and X-ray microscopy

The Niemann-Pick C2 protein (NPC2) is a sterol transfer protein in late endosomes and lysosomes (LE/LYSs). How its capacity to transport cholesterol between membranes is linked to endo-lysosomal membrane trafficking is not known. Using quantitative fluorescence imaging combined with soft X-ray tomography (SXT); we show that NPC2 mediated sterol efflux is accompanied by large changes in distribution, size and ultrastructure of endocytic organelles. We observed clearance of intra-luminal lipid deposits, a decrease in number of autophagosomes, formation of membrane contact sites (MCSs) to the endoplasmic reticulum and extensive tubulation of LE/LYSs in three-dimensional SXT reconstructions of NPC2 treated human fibroblasts. The cells could recycle the cholesterol analog dehydroergosterol (DHE) from LE/LYSs slowly also in the absence of NPC2 protein but internalized NPC2 synchronized and accelerated this process significantly. Most fluorescent NPC2 was retained in LE/LYSs while DHE was selectively removed from these organelles, at least partially by non-vesicular exchange with other membranes. During sterol efflux LE/LYSs were reallocated to the cell periphery, where they could fuse with newly formed endosomes. Surface shedding of micro-vesicles was found, suggesting a pathway for cellular sterol release. We conclude that NPC2 mediated sterol efflux from LE/LYSs controls membrane traffic through the endo-lysosomal pathway.

cell biology↗