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Pace, S.

Publications and source records attributed to Pace, S..

2 recordsLinked to original sources
bioRxiv2023

Cortical-brainstem circuitry attenuates stress reactivity

Exposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. Thus, a vmPFC-RVLM connection could represent a circuit mechanism linking stress appraisal and physiological reactivity. The current study investigated a direct vmPFC-RVLM circuit utilizing genetically-encoded anterograde and retrograde tract tracers. Together, these studies found that stress-reactive vmPFC neurons project to catecholaminergic neurons throughout the ventrolateral medulla in male and female rats. Next, we utilized optogenetic terminal stimulation to evoke vmPFC synaptic glutamate release in the RVLM. Photostimulating the vmPFC-RVLM circuit during restraint stress suppressed glycemic stress responses in males, without altering the female response. However, circuit stimulation decreased corticosterone responses to stress in both sexes. Circuit stimulation did not modulate affective behavior in either sex. Further analysis indicated that circuit stimulation preferentially activated non-catecholaminergic medullary neurons in both sexes. Additionally, vmPFC terminals targeted medullary inhibitory neurons. Thus, both male and female rats have a direct vmPFC projection to the RVLM that reduces endocrine stress responses, likely through the recruitment of local RVLM inhibitory neurons. Ultimately, the excitatory/inhibitory balance of vmPFC synapses in the RVLM may regulate stress reactivity as well as stress-related health outcomes. First author profileSebastian Pace is a Ph.D. candidate in the laboratory of Brent Myers at Colorado State University. Before beginning his Ph.D., Sebastian completed his B.S. and M.S. at the University of Texas-El Paso. While completing his M.S. he worked in the Karine Fenelon Lab. Sebastians current research project focuses on understanding how corticolimbic inputs to the medullary brainstem regulate sympathetic and neuroendocrine stress responses. Key points summaryO_LIGlutamatergic efferents from the ventromedial prefrontal cortex target catecholaminergic neurons throughout the ventrolateral medulla. C_LIO_LIPartially segregated, stress-responsive ventromedial prefrontal cortex populations innervate the rostral and caudal ventrolateral medulla. C_LIO_LIStimulating ventromedial prefrontal cortex synapses in the rostral ventrolateral medulla decreases stress-induced glucocorticoid release in males and females. C_LIO_LIStimulating ventromedial prefrontal cortex terminals in the rostral ventrolateral medulla preferentially activates non-catecholaminergic neurons. C_LIO_LIVentromedial prefrontal cortex terminals target medullary inhibitory neurons. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/549781v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@c362acorg.highwire.dtl.DTLVardef@1830ca5org.highwire.dtl.DTLVardef@b3411borg.highwire.dtl.DTLVardef@779392_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2020

Techno-economic assessment of animal cell-based meat

Interest in animal cell-based meat (ACBM) or laboratory grown meat has been increasing, however the economic viability of these potential products has not been thoroughly vetted. Recent studies suggest monoclonal antibody production technology can be adapted for the industrialization of ACBM production. This study provides a scenario-based assessment of the projected cost per kilogram of ACBM based on cellular metabolic requirements and process/chemical engineering conventions. A sensitivity analysis of the model identified the nine most influential cost factors for ACBM production out of 67 initial parameters. The results indicate that technological performance will need to approach technical limits for ACBM to achieve profitably as a commodity. However, the model also suggests that low-volume high-value specialty products could be viable based on current technology. One Sentence SummaryA model based upon cellular metabolism and engineering conventions was created to examine the economic viability of animal cell-based meat. Significance statementAnimal cell-based meat (ACBM) has received a significant amount of media attention (as well as corporate investment) in recent years based on its perceived potential to displace traditional meat production, whether beef, poultry, or fish. However, a robust techno-economic assessment (TEA) of these potential products is not publicly available. Our study examined the capital and operating expenditures for potential ACBM products based upon fundamental cellular attributes, the use of proposed near-term/existing technology, and process engineering conventions. Our findings suggest that the current production pathways are far from producing cost-competitive ACBM products, as well as highlight the technical metrics that must be achieved for an ACBM product to become economically viable.

bioengineering↗