Browsing by Subject "Animal sciences"

Wound healing is a vastly complicated process. While this can be said about many biological functions in the body, wounds present a particularly difficult problem due to their inherent irregularity or uniqueness. Because different wounds behave and heal differently, or not at all, different therapies must be developed to treat them effectively. The research presented here details several approaches to progress not only the entire field of wound healing research, but also focuses on hydrogel technology improvements. Using titanium 3D printing, cap-able splints were constructed to not only ease the surgical process but also enable efficient daily wound access for treatment administration or wound tracking over time without the need to completely undress and redress the wound. The titanium splints did prove effective for daily monitoring but did still require some surgical prowess. To remove the need for surgical skills, an adhesive wound splint was developed by incorporating ethoxylated polyethyleneimine (EO-PEI) into the traditional polydimethylsiloxane (PDMS) polymer recipe resulting in adhesive PDMS (aPDMS). The aPDMS splints drastically reduced surgery time per animal without compromising wound splinting performance. Traditional bulk hydrogels have been used in wound healing research but have yet to be clinically implemented in a widespread manner due in part to their resistance to cellular infiltration or integration with the host. Using hyaluronidase (HAase) on a hyaluronic acid (HA) based hydrogels to partially degrade the surface of bulk gels yielded a looser nano-scale mesh size that enhanced cellular infiltration into the gel and granted better access to nanoparticle therapy loaded within. Finally, a biologically active viscous salve loaded with heavy chains (HC) of the serum protein Inter-α Inhibitor (IαI) was designed to leverage HC’s ability to mitigate the inflammatory response such that normal wound healing regeneration could ensue.

Making decisions is fundamental to everything we do, yet it can be impaired in various disorders and conditions. While research into the neural basis of decision-making has flourished in recent years, many questions remain about how decisions are instantiated in the brain. Here we explored how primates make abstract decisions and decisions in social contexts, as well as one way to non-invasively modulate the brain circuits underlying decision-making. We used rhesus macaques as our model organism. First we probed numerical decision-making, a form of abstract decision-making. We demonstrated that monkeys are able to compare discrete ratios, choosing an array with a greater ratio of positive to negative stimuli, even when this array does not have a greater absolute number of positive stimuli. Monkeys’ performance in this task adhered to Weber’s law, indicating that monkeys—like humans—treat proportions as analog magnitudes. Next we showed that monkeys’ ordinal decisions are influenced by spatial associations; when trained to select the fourth stimulus from the bottom in a vertical array, they subsequently selected the fourth stimulus from the left—and not from the right—in a horizontal array. In other words, they begin enumerating from one side of space and not the other, mirroring the human tendency to associate numbers with space. These and other studies confirmed that monkeys’ numerical decision-making follows similar patterns to that of humans, making them a good model for investigations of the neurobiological basis of numerical decision-making.

We sought to develop a system for exploring the neuronal basis of the cognitive and behavioral effects observed following transcranial magnetic stimulation, a relatively new, non-invasive method of brain stimulation that may be used to treat clinical disorders. We completed a set of pilot studies applying offline low-frequency repetitive transcranial magnetic stimulation to the macaque posterior parietal cortex, which has been implicated in numerical processing, while subjects performed a numerical comparison and control color comparison task, and while electrophysiological activity was recorded from the stimulated region of cortex. We found tentative evidence in one paradigm that stimulation did selectively impair performance in the number task, causally implicating the posterior parietal cortex in numerical decisions. In another paradigm, however, we manipulated the subject’s reaching behavior but not her number or color comparison performance. We also found that stimulation produced variable changes in neuronal firing and local field potentials. Together these findings lay the groundwork for detailed investigations into how different parameters of transcranial magnetic stimulation can interact with cortical architecture to produce various cognitive and behavioral changes.

Finally, we explored how monkeys decide how to behave in competitive social interactions. In a zero-sum computer game in which two monkeys played as a shooter or a goalie during a hockey-like “penalty shot” scenario, we found that shooters developed complex movement trajectories so as to conceal their intentions from the goalies. Additionally, we found that neurons in the dorsolateral and dorsomedial prefrontal cortex played a role in generating this “deceptive” behavior. We conclude that these regions of prefrontal cortex form part of a circuit that guides decisions to make an individual less predictable to an opponent.

Primates are an order of mammals that lack claws. Therefore, arboreal primates must apply opposing pressures with their digits to grasp supports and move through their habitats. This requirement may affect the mechanics of specific aspects of arboreal travel, such as descent, in the locomotion of primates compared to clawed non-primates, and may have influenced the evolutionary selective pressures that primates experienced over time. It has been hypothesized that larger primates are less likely to descend supports headfirst than smaller primates and clawed non-primates, however, this phenomenon has never been considered in a comparative context. Knowing how body size, anatomical proportions, and environment interact to affect locomotor behaviors is central to linking morphology with behavior, such as when evaluating hypotheses of primate origins.

This thesis analyzed descending locomotion in nine species of strepsirrhine primates that occupy four locomotor categories: large arboreal generalists, representing above branch quadrupeds weighting over 1 kg; small arboreal generalists, representing above branch quadrupeds under 1 kg; slow climbers; and vertical clingers and leapers. Primates were video recorded moving on supports ranging from horizontal to vertical in 15° increments. I tested specific hypotheses about gait and kinematic changes in response to declines that have been observed in primates moving down supports as steep as approximately 30° to see if these patterns would be replicated in primates moving on steeper support orientations.

I found that primates under 1 kg always used headfirst descent on all supports. For primates above 1 kg, body size appeared to be an important factor in determining behavior, but it also appeared that anatomical differences might have enabled one of the largest species in the sample, Varecia variegata, to perform vertical headfirst descent, while relatively smaller species like Lemur catta were not observed to use this behavior on supports greater than 45°. Within these large arboreal generalists, increases to individual age also seemed to drive behaviors away from headfirst descent in favor of tail first descent. Frequencies of headfirst descent were compared to other mechanisms of descent, such as tail first descent, were scored for a total of 3139 observed descents. These observations were incorporated into a Bayesian multilevel model that included information on the support condition (including orientation and diameter), morphological information for each species (average intermembral index and foot proportions), as well as individual mass and age. The model was then used to predict the probability of headfirst descent on various supports in simulated ancestral primates that exemplified different hypotheses of primate origins. It was found that features including body mass, support orientation, and foot and limb proportions greatly affected the predicted probabilities of headfirst descent. Large primates with lower intermembral indices and smaller feet were least likely to use headfirst, especially as supports became more steeply angled. Species that were smaller, with relatively longer arms or larger feet tend to use headfirst descent most frequently, even on vertical supports. The model predicted less headfirst descent in the very smallest primates on near horizontal supports, driven by observations of leaping in the smallest species in this sample.

Headfirst descents were analyzed for footfall patterns to evaluate temporal aspects of gait, and to test the hypothesis that limb phase should decrease as supports become steeper and that contact period with the support should increase, and relatively more so for the forelimbs than hind limbs. It was found that limb phase did significantly decrease across the sample as support orientation became steeper, and that both forelimb and hind limb contact times increased as proportion of the total stride period, although the forelimb did not increase relatively more than the hind limb in many species.

Headfirst descents were then analyzed for changes to kinematic aspects of gait including effective limb length, joint angles at key points during the stride, limb excursions, and velocity. I found that as supports became steeper primates across the sample reduced trunk inclination bringing the body parallel to the support and reducing the distance of the center of mass from the support, consistent with pitch-avoidance strategies. The forelimb remained compliant and highly protracted with increasing support orientation; the hind limb did not remain complaint and instead became significantly retracted in primates travelling on supports of 60° and steeper. Speed was generally reduced as support orientation increased.

Overall this study demonstrated that strepsirrhine primates capable of headfirst descent span a range of body masses up to approximately 4 kg in this sample. Across this range of body masses common strategies for traveling headfirst on supports included adopting slow trotting gaits with extended periods of hind limb retraction and forelimb protraction. Species that did not perform headfirst descent may have been limited in their ability to perform this behavior by aspects of their anatomy, such as having relatively short arms or less developed muscles for pedal grasping compared to species that were more adept at headfirst descent.

Placing these results into an evolutionary context, a small primate ancestor would be least impacted in its ability to navigate using headfirst descent on supports of all angles, whereas a larger ancestral primate might have been limited in the arboreal supports it could have navigated headfirst. Leaping may have been an alternative to grasping mediated headfirst descent in very small early primates, while alternatives to headfirst descent, such as tail first decent, that were only observed in larger species might have emerged later as various primate lineages increased in body mass but retained the characters of primate origins, grasping feet and nails.

Vertebrate animals undergo a constellation of physiological responses when they experience submersion. These responses, collectively known as the dive response, include apnea (breath-hold), bradycardia (a reduction in heart rate), and peripheral vasoconstriction (the restriction of oxygenated blood to organs critical to life). Cetaceans, the order of mammals that includes whales, dolphins, and porpoise, are obligate air-breathing mammals and one of the few mammalian taxa to become fully aquatic. Given this evolutionary trajectory, cetaceans are an excellent model for investigating the physiological extremity of the dive response.

One limiting factor in dive response research involving cetaceans is the relative lack of non-invasive physio-logging devices that can be attached in free-swimming animal contexts. To address this gap, my collaborators and I invented a new multi-sensor, suction cup-attached device called the FaunaTag. The FaunaTag was custom-built to enable non-invasive collection of cardiovascular physiological data in cetacean species. Equipped with a novel contact sensor column that interfaces with the body surface of the tagged animal, the FaunaTag's near-infrared spatially-resolved diffuse reflectance bio-optical sensor and its accelerometer and gyroscope sensors were used to investigate aspects of the dive response in bottlenose dolphins (Tursiops truncatus), the most accessible and well-studied member of the cetacean order.

In the first set of experimental trials, I used the FaunaTag and a new methodological approach to investigate the extent to which dolphin cardiac heart rate changes during alternating bouts of stationary surface free-breathing and submerged apnea. In these trials, the FaunaTag and its unique contact sensor measured the vibrations associated with the cardiac cycle at the dolphin's chest wall. These vibrations were used to compute instantaneous heart rate and instantaneous kinetic energy associated with cardiac contractility. During these trials, we also tested the efficacy of the FaunaTag's near-infrared bio-optical sensor to measure dolphin heart rate before, during, and after apnea, with the FaunaTag placed at a variety of body locations, and the extent to which optically-computed heart rate estimates matched the cardiac frequency estimates calculated from cardiac vibrations.

I found that instantaneous heart rate estimates measured in this study were consistent with the heart rates computed using electrocardiography in previous studies involving these same animals. I also observed expected patterns of bradycardia during extended apneas, respiratory sinus arrhythmias following respiration events, and a return to a baseline heart rate shortly after respiration. I also found that instantaneous kinetic energy of cardiac contraction varies between free-breathing and breath-holding trial phases, with a decline to a stable apneic baseline during submerged breath-holds, followed by a steep rise following cessation of apnea and an eventual return to a variable but reduced post-apnea baseline. The FaunaTag's near-infrared spectroscopy performed poorly at dorsal body locations, detected 60% of the matched heartbeats while attached to the cardiac window of the bottlenose dolphin, and achieved a match rate exceeding 90% in the best trial. Future efforts involving the FaunaTag will feature an improved bio-optical sensing module which may resolve poor optical cardiography at the dorsal surfaces of the dolphin body and other cetacean species.

The deleterious effects of inbreeding have been well-documented in both captive and wild populations. Mechanisms of inbreeding avoidance such as mate choice and sex-biased dispersal have also been documented across a variety of taxa. However, studies of inbreeding avoidance via mate choice are surprisingly scarce, and those that explicitly compare maternal and paternal kin are entirely absent in mammals. Here, we provide the first study to assess how behavioral inbreeding avoidance varies across kin classes in a population of wild baboons. We first examine the series of isolating barriers that prevent inbreeding, including death, dispersal, and mate choice, and we next use pedigree data to assess how behavioral inbreeding avoidance varies across kin classes. We found that while the demographic barriers of death and male-biased dispersal are extremely effective in limiting inbreeding in this population, we still found strong evidence for inbreeding avoidance via mate choice. In particular, while most kin classes exhibited inbreeding avoidance, maternal kin (mother-son pairs, maternal siblings) were more avoidant than paternal kin (father-daughter pairs, paternal siblings) despite having identical coefficients of relatedness. Finally, by taking advantage of a natural experiment in our study population, we also found that social groups with reduced sex-biased dispersal and reduced inbreeding avoidance via mate choice produced ten times as many inbred offspring.

Homo sapiens’ capacity for cooperative communication enables us adapt to new environments more rapidly than any other species via the process of cumulative cultural evolution, but the evolutionary processes which led to this capacity remain an open question (Boyd & Richerson, 1995; Henrich & McElreath, 2003; Hill et al., 2009; Mesoudi & Thornton, 2018; Tomasello, 1999). One proposed explanation for this capacity is the human self-domestication hypothesis (SDH), which posits that cooperative communication was altered via shifts in development as a by-product of self-selecting against aggression and for prosociality (Hare, 2017; Hare et al., 2012). Dogs have been hypothesized to have undergone the same process during their domestication, resulting in human-like cooperative communicative abilities (Hare, 2017). If so, this convergence could make dogs a critical model for human self-domestication. The present dissertation evaluates this hypothesis by testing three resulting predictions: 1) that dogs’ understanding of communicative intentions is actually “human-like” (i.e. spontaneous and flexible), which we tested through a series of gesture reading tasks with adult dogs; 2) that these qualities are a result of domestication, and therefore expressed more strongly and at an earlier age in dogs compared to wolves, which we tested by running dog and wolf puppies through a cross-sectional battery of cognitive and temperament tasks; and 3) that dogs show early emerging and expanded windows of social development relative to other non-social cognitive abilities, indicating a similar developmental pattern as is observed in humans, which we tested by running puppies through a longitudinal battery containing nine cognitive tasks during the period of rapid brain development. Strong support was found for predictions 1 and 2, and some support was found for prediction 3, with more work being needed to draw stronger conclusions. We conclude that dogs’ cooperative communicative abilities are convergent with those of humans at the levels of behavior, cognition, and potentially development as well.