The Major Histocompatibility Complex in Song Sparrows: Immunity, Signals, and Mate Choice

In recent years, sexual selection theory has redefined genetic quality to consider not only additive genetic effects on fitness but also non-additive genetic effects, such as heterozygote advantage or disadvantage. In jawed vertebrates, the major histocompatibility complex (MHC) gene family has been shown to exhibit both additive and non-additive genetic effects on fitness. MHC gene products are involved in initiating adaptive immune responses, and MHC genotype determines the range of pathogens to which an individual can respond. Therefore, parasite-mediated selection at MHC may favour locally-adapted, rare, or particular combination of alleles. Because heterozygote advantage at MHC is widespread, sexual selection should favour mechanisms by which individuals assess the MHC genotypes of potential mates, and mate non-randomly. Studies exploring the role of MHC in immunity and sexual selection are widespread amongst mammals and fish, but in birds (especially songbirds) there is relatively scant evidence for MHC-mediated mating and the mechanism by which this might be accomplished remains unknown. First, I assessed differentiation at MHC class I and II that might underlie locally-good gene effects in two populations of song sparrows (Melospiza melodia) previously shown to exhibit higher resistance to sympatric malaria (Plasmodium) strains. I found no population differentiation, suggesting no locally-good gene effects at MHC, but individuals with higher class I diversity were less likely to be infected when experimentally inoculated with Plasmodium. Second, I explored whether song sparrows convey information on MHC class II genotype through chemical (preen oil) or auditory (birdsong) cues. Pairwise similarity at MHC was related to pairwise similarity of preen oil chemical composition, but not to pairwise similarity in song repertoire content. Song repertoire size, a sexually selected trait in this species, was nonlinearly related to MHC diversity, such that males with intermediate MHC diversity sang the most songs. Finally, to investigate MHC-mediated mate choice, I compared MHC similarity of socially mated pairs of free-living song sparrows to random expectations. Contrary to my prediction of MHC-disassortative mating, social pairs were more similar at MHC than expected by chance. This work emphasizes the importance of considering mate choice in the context of fitness effects at MHC

Random subgraphs of finite graphs: I. The scaling window under the triangle condition

We study random subgraphs of an arbitrary finite connected transitive graph $\mathbb G$ obtained by independently deleting edges with probability $1-p$. Let $V$ be the number of vertices in $\mathbb G$, and let $\Omega$ be their degree. We define the critical threshold $p_c=p_c(\mathbb G,\lambda)$ to be the value of $p$ for which the expected cluster size of a fixed vertex attains the value $\lambda V^{1/3}$, where $\lambda$ is fixed and positive. We show that for any such model, there is a phase transition at $p_c$ analogous to the phase transition for the random graph, provided that a quantity called the triangle diagram is sufficiently small at the threshold $p_c$. In particular, we show that the largest cluster inside a scaling window of size |p-p_c|=\Theta(\cn^{-1}V^{-1/3}) is of size $\Theta(V^{2/3})$, while below this scaling window, it is much smaller, of order $O(\epsilon^{-2}\log(V\epsilon^3))$, with \epsilon=\cn(p_c-p). We also obtain an upper bound O(\cn(p-p_c)V) for the expected size of the largest cluster above the window. In addition, we define and analyze the percolation probability above the window and show that it is of order \Theta(\cn(p-p_c)). Among the models for which the triangle diagram is small enough to allow us to draw these conclusions are the random graph, the $n$-cube and certain Hamming cubes, as well as the spread-out $n$-dimensional torus for $n>6$

Hackle spectral characteristics and their role in mate choice in European starlings (Sturnus vulgaris)

ix, 74 leaves : ill. ; 29 cm.Includes abstract.Includes bibliographical references (leaves 66-74).Plumage spectral characteristics are thought to play an essential role in mate choice. Male and female birds may benefit from mating outside of their social-pair bond if they obtain genetic benefits for their offspring by choosing mates with plumage that signals individual high quality. The goal of this thesis was to test the hypothesis that male and female genetic quality is signaled through hackle spectral characteristics and used in mate choice decisions by European starlings (Sturnus vulgaris). Hackle brightness was positively correlated with female body condition and male provisioning effort. Also males with brighter hackles sired proportionally more male offspring than males with duller hackles. Purple hackles were positively correlated with male body condition and female realized reproductive success. This study demonstrates the importance of hackle spectral quality in European starlings and the role it plays in mate choice

Subjective Sleep Quality Deteriorates Before Development of Painful Temporomandibular Disorder

There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the OPPERA prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every three months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n=220) and matched TMD-free controls (n=193). Subjective sleep quality deteriorated progressively, but only in those who subsequently developed TMD. A Cox proportional hazards model showed that risk of TMD was greater among participants whose sleep quality worsened during follow-up (adjusted hazard ratio=1.73, 95% confidence limits: 1.29, 2.32). This association was independent of baseline measures of sleep quality, psychological stress, somatic awareness, comorbid conditions, non-pain facial symptoms and demographics. Poor baseline sleep quality was not significantly associated with baseline pain sensitivity or with subsequent change in pain sensitivity. Furthermore the relationship between sleep quality and TMD incidence was not mediated via baseline pain sensitivity nor change in pain sensitivity

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions: the OPPERA study

The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). However, anatomical criteria overlook etiology, potentially hampering treatment decisions. This study identified clusters of individuals using a comprehensive array of biopsychosocial measures. Data were collected from a case–control study of 1031 chronic TMD cases and 3247 TMD-free controls. Three subgroups were identified using supervised cluster analysis (referred to as the adaptive, pain-sensitive, and global symptoms clusters). Compared with the adaptive cluster, participants in the pain-sensitive cluster showed heightened sensitivity to experimental pain, and participants in the global symptoms cluster showed both greater pain sensitivity and greater psychological distress. Cluster membership was strongly associated with chronic TMD: 91.5% of TMD cases belonged to the pain-sensitive and global symptoms clusters, whereas 41.2% of controls belonged to the adaptive cluster. Temporomandibular disorder cases in the pain-sensitive and global symptoms clusters also showed greater pain intensity, jaw functional limitation, and more comorbid pain conditions. Similar results were obtained when the same methodology was applied to a smaller case–control study consisting of 199 chronic TMD cases and 201 TMD-free controls. During a median 3-year follow-up period of TMD-free individuals, participants in the global symptoms cluster had greater risk of developing first-onset TMD (hazard ratio = 2.8) compared with participants in the other 2 clusters. Cross-cohort predictive modeling was used to demonstrate the reliability of the clusters

Temporal change in headache and its contribution to the risk of developing first-onset temporomandibular disorder in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study

While cross-sectional studies have demonstrated an association between headache and temporomandibular disorder (TMD), whether headache can predict the onset of TMD is unknown. The aims of this study were to evaluate the contribution of headache to the risk of developing TMD and describe patterns of change in headache types over time. An initially TMD-free cohort of 2410 persons with low frequency of headache completed quarterly questionnaires assessing TMD and headache symptoms over a median 3.0-year follow-up period. First-onset TMD was confirmed by clinical examination in 199 participants. Baseline reports of migraine (hazard ratio [HR] = 1.67, 95% confidence interval [CI]: 1.06-2.62) or mixed headache types (HR = 4.11, 95% CI: 1.47-11.46), or headache frequency (HR = 2.13, 95% CI: 1.31-3.48) predicted increased risk of developing TMD. In addition, headache dynamics across the follow-up period before the TMD onset were evaluated in a nested case-control study where 248 incident TMD cases were matched to 191 TMD-free controls. Both headache prevalence and frequency increased across the observation period among those who developed TMD but not among controls. Patients with TMD were more likely to experience worsening in the headache type compared with that by controls, eg, prevalence of definite migraine among TMD cases increased 10-fold. Among all headache types experienced by patients with TMD before the TMD onset, migraine had the highest odds of progression relative to remission (odds ratio = 2.8, 95% CI: 1.6-4.8), whereas for controls this ratio was significant only for the tension-type headache (odds ratio = 2.1, 95% CI: 1.2-3.9). The important clinical implication of these findings is that adequate treatment of migraine may reduce the risk for developing TMD

Modification of COMT-dependent pain sensitivity by psychological stress and sex

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity

OPPERA Study Identifies an Association Between the Use of Hormonal Contraceptives and Orofacial Pain and Headaches

Introduction: • Hormone therapy has been described as a risk factor for chronic pain conditions such as low back pain and temporomandibular disorders (TMD)• Hormonal contraception (HC) may affect pain by altering the function of the endogenous opioid system and augmenting serotonin metabolism • HC has been shown to increase experimental heat and ischemic pain sensitivity in women with TMD and migraine headaches • Women using HC also demonstrate decreased pressure pain and tactile thresholds of the temporalis and masseter muscles compared to healthy women not using HC • An association between the use of HC and painful conditions such as migraine headaches and TMD has been described in previous studies although the nature of this association remains unclear • This analysis sought to determine the relationship between HC use and painful symptoms (particularly headaches and orofacial pain