Biology subjects

Drake, L.

Publications and source records attributed to Drake, L..

5 recordsLinked to original sources

bioRxiv2026

Mechanosensitive Piezo Channels Contribute to Airway Changes in Chronic Obstructive Pulmonary Disease

As an intrinsically mechanosensitive organ, the lung experiences a range of mechanical forces. Chronic obstructive pulmonary disease (COPD) involves abnormal macroscopic cellular and extracellular matrix (ECM) changes that impact mechanical properties of the lung. Mechanosensitive Piezo1/2 channels are expressed in the lung including on airway smooth muscle cells (ASM) that mediate cellular responses to stretch and ECM biomechanics. The expression and roles of Piezos in COPD lung ASM are not known. We hypothesized that Piezo expression and activation are altered in COPD lung ASM influencing ECM regulation. Distribution of Piezo proteins in ASM and epithelium of small airways of COPD stage II and IV vs. non-COPD controls was assessed using immunohistochemistry and ImageJ (n=10-17/group). Isolated ASM cells from control (n=6) vs. COPD stage II and IV patients (n=3 each stage) were exposed to stretch or the Piezo1 agonist Yoda1 followed by measurement of ECM gene and protein expression. Less Piezo2 staining was observed in COPD IV patients compared to controls, with lesser area and intensity of staining in the epithelial layer, and lower intensity of staining in ASM and small airways as a whole. Fura-2-based imaging of ASM Ca2+ showed lower influx after Yoda1 exposure in COPD II compared to control and COPD IV. Gene expression of Piezo1 increased upon stretching in controls but not in COPD ASM, while Piezo2 protein expression decreased with stretching in all groups. Yoda1 treatment resulted in decreased collagen1, fibulin1 and periostin gene and collagen 1 and periostin protein expression in ASM. Overall, these results support a role for Piezo activation in abnormal ECM-ASM cell crosstalk in COPD.

physiology↗

bioRxiv2026

Molecular methods reveal responses of bacterial communities, including indicator species, to ballast water management

Ballast water (BW) is an important vector for the global translocation of bacterial taxa, including pathogens. Legal frameworks establishing limits on the discharge of live organisms into recipient environments have been designed to reduce risks of microbial invasions, and understanding the impacts of BW management on bacterial communities is critical for assessing the effectiveness of these practices. Here we evaluate changes in bacterial communities associated with both BW treatment (BWT) and a combined management approach of BWT plus BW exchange (BWT+E). Samples were collected on two experimental voyages designed specifically to compare BW-associated biota before and after management. Microbial community structure and inferred function were assessed based on high throughput sequencing of 16S rRNA amplicons, and bacterial indicator taxa E. coli and enterococci were analyzed using targeted qPCR. As expected, both BWT alone and BWT+E dramatically changed bacterial communities, with the latter resulting in the largest overall decreases in bacterial diversity. Increases in Gammaproteobacteria, especially in the genus Pseudomonas, were particularly notable, with concomitant decreases in Alphaproteobacteria and Bacteroidia. Shifts in predicted bacterial function associated with BWT were similar for both voyages, despite significant differences in community structure, and may represent selection for r-strategists capable of active regrowth after BWT. qPCR estimates of indicator taxa were similar to those obtained through standard culture methods but may offer increased sensitivity for detecting changes associated with management. Our results indicate that BW management is effective at reducing bacterial communities but suggest that further research is needed to understand risks associated with taxa that may survive BWT.

ecology↗

bioRxiv2026

Granule cells reorient cortical manifolds to separate contexts but preserve their geometry

To learn effectively, animals must generalize across yet distinguish between related contexts. Generalization relies on low-dimensional neural manifolds found throughout the neocortex1,2, which accelerate learning by constraining neural activity to task-relevant axes3. Conversely, context separation is attributed to neural expansion layers that can project information into high-dimensional feature spaces4,5, most famously cerebellar granule cells (GrCs)6-8. To investigate the generalization-separation tradeoff, we simultaneously imaged key nodes in the universal cortico-cerebellar pathway9--premotor layer 5 pyramidal tract (L5PT) and GrCs--during parallel learning of two distinct skills with shared temporal structure. Rather than expanding the cortical representations, GrCs retained their low-rank encoding of each task. Across contexts, despite stable cortico-cerebellar coupling, L5PT activity patterns generalized while GrC patterns temporally remapped. But rather than independently scrambling, GrC populations remapped coherently: their low-dimensional trajectories "rotated" apart between tasks, separating the contexts while preserving the cortical geometry of each. Moreover, GrC trajectories diverged most strongly in expert animals. This suggests a fundamental architectural division of labor: the cortex provides invariant dynamic primitives for smooth generalization, while cerebellar activity reconfigures them to drive context-specific output.

neuroscience↗

bioRxiv2026

Cerebellar circuits anticipate dopamine rewards

Learning motivated behaviors requires both anticipating rewards and reinforcing actions that yield them. Although cerebellar activity encodes natural rewards like water and food, it also coordinates physical movements like eating and drinking. To disentangle reward from consummatory movements, we trained mice to push for delayed dopamine rewards delivered directly into the brain. Here we show that cerebellar input streams use both predictive and instructive codes for dopamine reward. Two-photon imaging revealed that many cerebellar granule cells (GrCs) predictively encoded dopamine rewards with sustained activity that "stretched" to match 1- or 2-s delay intervals before terminating upon reward receipt. By contrast, most cerebellar climbing fibers (CFs) spiked just after dopamine delivery. In mice also trained with water rewards, encoding strength for dopamine matched or exceeded that for water. Both cell types contributed causally: chronic GrC inhibition disrupted self- stimulation learning, and CF self-stimulation "rewards" drove moderate operant learning in naive animals. Thus, cerebellar encoding of dopamine reward helps drive motivated behavior, suggesting deeper cerebellar integration in brain reward prediction networks.

neuroscience↗

bioRxiv2021

Succinate Dehydrogenase (SDH)-subunit C regulates muscle oxygen consumption and fatigability in an animal model of pulmonary emphysema.

Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force-generation capacity which partially depends on fibers oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of succinate dehydrogenase (SDH) subunit C in association with lower oxygen consumption and fatigue-tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema and we found that SDHC is required to support respiration in cultured muscle cells. Moreover, in-vivo gain of SDH function in emphysema animals muscles resulted in better oxygen consumption rate (OCR) and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers, and a reduced amount of 2B fibers. Our data suggests that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful to develop strategies aimed at attenuating this comorbidity.

physiology↗