Tag: Oral Session 4 S

Rationalizing the Ratio Difference: Analysis of Molecular Factors Related to Primate Skeletal Muscle Fiber Type

Presenter(s): Frankie Lewis

Faculty Mentor(s): Kirstin Sterner

Oral Session 4 S

Bipedalism is a defining human characteristic, and many distinctive human traits increase efficiency when walking or running. While most research has focused on the skeleton, fewer people have investigated the role of muscular changes on human bipedal evolution. In muscle, slow-twitch fibers produce energy more efficiently and are better for endurance activities, whereas fast-twitch fibers consume more energy and are advantageous for activities requiring short bursts of power. In general, quadrupeds have more fast-twitch fibers and bipeds have more slow-twitch fibers, but it is still unclear how evolution shaped these patterns. My research addressed this gap in knowledge by characterizing a set of candidate genes that encode proteins that play a role in fiber type. First, I compared the protein-coding sequences of five candidate genes in 23 primates to test if differences at the DNA level are associated with differences in locomotion. Second, I tested if these genes are expressed differently in the muscle tissue of quadrupeds vs. bipeds. The structure of each muscle fiber is generally conserved between species, whereas the abundance ratio is not. Therefore, I predicted that differential expression, not sequence variation, is the main source of the fiber-type ratio variation. Preliminary data suggests these genes are highly conserved and there are a number of differentially expressed genes in primate muscle tissue. Reconstructing the evolutionary history of this trait is important for understanding the evolution of human bipedalism and identifying genes involved in fiber type may also inform our understanding of muscular diseases.

Exercise-induced Elevations in Skeletal Muscle Histamine Contributes to Increased Post- exercise Capillary Permeability

Exercise-induced Elevations in Skeletal Muscle Histamine Contributes to Increased Post- exercise Capillary Permeability

Chaucie Edwards

Faculty Mentor(s): John Halliwill & Matthew Ely

Oral Session 4 S

Histamine, an endogenously released molecule in immune and inflammatory responses increases local vasodilation, blood flow, and capillary permeability. During exercise, histamine is produced within exercising muscle and contributes to an elevated post-exercise blood flow. The histamine-induced post-exercise vasodilation is contained within previously exercised muscle as histamine concentrations are not elevated in non-exercised muscle (i.e. arms during leg exercise). It is unknown if intramuscular histamine also contributes to elevate capillary permeability following exercise. PURPOSE: To compare capillary permeability of the leg before and after prolonged unilateral knee-extension exercise under normal conditions and when histaminergic signaling is blocked. It was hypothesized that H1/H2 receptor antihistamines would decrease capillary permeability following exercise in an exercised leg but not in a resting leg. METHODS: Six (2F) volunteers performed 60 min of unilateral knee-extension exercise at 60% of peak power after consuming either Placebo or histamine (H1/H2) receptor antagonists (Blockade). A capillary filtration coefficient (CFC) reflecting the rate of change in limb girth per rise in venous pressure was calculated using venous occlusion plethysmography. A CFC was calculated prior to (PRE) and following (POST) exercise in both the exercised leg (EL) and the resting leg (RL). Data were analyzed with a 3-way RM ANOVA and presented as Means±SEM. RESULTS: On average, CFC increased 161±90% (PRE: 2.5±1.0 to POST: 6.6±2.3 μg·100g-1·min- 1·mmHg-1) in the EL and 38±31% (PRE: 4.8 to POST: 6.5 μg·100g-1·min-1·mmHg-1) in the RL during Placebo. Blockade attenuated the exercise-induced rise in CFC in the EL to 13±41% (PRE = 4.3±1.3 to POST = 4.9±1.8 μg·100g-1·min-1·mmHg-1) and in the RL 2±45% (PRE: 3.8±1.4 to POST: 3.8±1.7 μg·100g-1·min-1·mmHg-1). Due to the high variability in the measures there was a trend for CFC to increase with exercise (P=0.161), for Blockade to attenuate the rise in CFC (P=0.363), and for a leg by drug interaction (P=0.289). CONCLUSION: These initial data suggest that exercise-induced histamine production contributes to the elevated CFC within exercised limbs.

Intestinal Phenotypes of Zebrafish Enteric Nervous System Double Mutants

Presenter(s): Lilly Carroll

Faculty Mentor(s): Judith Eisen & Kristi Hamilton

Oral Session 4 S

The enteric nervous system (ENS) innervates the intestine and regulates the dynamic intestinal environment. ENS reduction causes Hirschsprung disease (HSCR), a genetically complex disease that results in intestinal dysmotility and, in many patients, intestinal inflammation. The zebrafish is an excellent model in which to study the relationship between inflammation and genes linked to HSCR. Zebrafish with a mutation in one HSCR gene, sox10, have fewer enteric neurons and develop microbiota-dependent intestinal inflammation. Zebrafish with a mutation in another HSCR gene, ret, also have fewer ENS neurons but do not exhibit increased intestinal inflammation. To investigate the opposing intestinal phenotypes of sox10 and ret mutants, I analyzed intestinal phenotypes of sox10;ret double mutants. Because sox10 acts in neural crest cells that form the ENS and ret acts later, within ENS cells, I hypothesized that intestinal inflammatory phenotypes of sox10;ret double mutants would resemble those of sox10 mutants. To test this hypothesis, I quantified intestinal inflammation in sox10;ret double mutants by counting intestinal neutrophils. Surprisingly, I observed a wild-type (WT) neutrophil abundance phenotype in sox10;ret mutants. This result led me to investigate intestinal enterochromaffin cells, which produce serotonin and express ret but not sox10. I hypothesized that sox10;ret double mutants would exhibit the same decreased enterochromaffin cell phenotype as ret mutants. However, sox10;ret mutants had more enterochromaffin cells that ret mutants and were similar to WT. This result prompts further exploration of the potential interactions of the mutated genes for insights into the role of the ENS in maintenance of intestinal health.