Myasthenia gravis and related disorders: Pathology and molecular pathogenesis.

Disorders affecting the presynaptic, synaptic, and postsynaptic portions of the neuromuscular junction arise from various mechanisms in children and adults, including acquired autoimmune or toxic processes as well as genetic mutations. Disorders include autoimmune myasthenia gravis associated with acetylcholine receptor, muscle specific kinase or Lrp4 antibodies, Lambert-Eaton myasthenic syndrome, nerve terminal hyperexcitability syndromes, Guillain Barré syndrome, botulism, organophosphate poisoning and a number of congenital myasthenic syndromes. This review focuses on the various molecular and pathophysiological mechanisms of these disorders, characterization of which has been crucial to the development of treatment strategies specific for each pathogenic mechanism. In the future, further understanding of the underlying processes may lead to more effective and targeted therapies of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

Acoustic profiling in a complexly social species, the American crow: caws encode information on caller sex, identity, and behavioural context.

Previous research on inter-individual variation in the calls of corvids has largely been restricted to single call types, such as alarm or contact calls, and has rarely considered the effects of age on call structure. This study explores structural variation in a contextually diverse set of "caw" calls of the American crow (Corvus brachyrhynchos), including alarm, foraging recruitment and territorial calls, and searches for structural features that may be associated with behavioural context and caller sex, age, and identity. Automated pitch detection algorithms are used to generate 23 pitch-related and spectral parameters for a collection of caws from 18 wild, marked crows. Using principal component analysis and mixed models, we identify independent axes of acoustic variation associated with behavioural context and with caller sex, respectively. We also have moderate success predicting caller sex and identity from call structure. However, we do not find significant acoustic variation with respect to caller age.

Temperament in rhesus, long-tailed, and pigtailed macaques varies by species and sex.

Temperament differs among individuals both within and between species. Evidence suggests that differences in temperament of group members may parallel differences in social behavior among groups or between species. Here, we compared temperament between three closely related species of monkey-rhesus (Macaca mulatta), long-tailed (M. fascicularis), and pigtailed (M. nemestrina) macaques-using cage-front behavioral observations of individually housed monkeys at a National Primate Research Center. Frequencies of 12 behaviors in 899 subjects were analyzed using a principal components analysis to identify temperament components. The analysis identified four components, which we interpreted as Sociability toward humans, Cautiousness, Aggressiveness, and Fearfulness. Species and sexes differed in their average scores on these components, even after controlling for differences in age and early-life experiences. Our results suggest that rhesus macaques are especially aggressive and unsociable toward humans, long-tailed macaques are more cautious and fearful, and pigtailed macaques are more sociable toward humans and less aggressive than the other species. Pigtailed males were notably more sociable than any other group. The differences observed are consistent with reported variation in these species' social behaviors, as rhesus macaques generally engage in more social aggression and pigtailed macaques engage in more male-male affiliative behaviors. Differences in predation risks are among the socioecological factors that might make these species-typical behaviors adaptive. Our results suggest that adaptive species-level social differences may be encoded in individual-level temperaments, which are manifested even outside of a social context. Am. J. Primatol. 75:303-313, 2013. © 2012 Wiley Periodicals, Inc.

Population genetics of the Washington National Primate Research Center's (WaNPRC) captive pigtailed macaque (Macaca nemestrina) population.

Pigtailed macaques (Macaca nemestrina) provide an important model for biomedical research on human disease and for studying the evolution of primate behavior. The genetic structure of captive populations of pigtailed macaques is not as well described as that of captive rhesus (M. mulatta) or cynomolgus (M. fascicularis) macaques. The Washington National Primate Research Center houses the largest captive colony of pigtailed macaques located in several different housing facilities. Based on genotypes of 18 microsatellite (short tandem repeat [STR]) loci, these pigtailed macaques are more genetically diverse than captive rhesus macaques and exhibit relatively low levels of inbreeding. Colony genetic management facilitates the maintenance of genetic variability without compromising production goals of a breeding facility. The periodic introduction of new founders from specific sources to separate housing facilities at different times influenced the colony's genetic structure over time and space markedly but did not alter its genetic diversity significantly. Changes in genetic structure over time were predominantly due to the inclusion of animals from the Yerkes National Primate Research Center in the original colony and after 2005. Strategies to equalize founder representation in the colony have maximized the representation of the founders' genomes in the extant population. Were exchange of animals among the facilities increased, further differentiation could be avoided. The use of highly differentiated animals may confound interpretations of phenotypic differences due to the inflation of the genetic contribution to phenotypic variance of heritable traits.

Aggression in pigtailed macaque (Macaca nemestrina) breeding groups affects pregnancy outcome.

Past research has shown that aggressive behaviors can affect female reproductive outcome in nonhuman primate captive breeding programs. In this study, aggressive behaviors were recorded in a colony of pigtailed macaque monkeys (Macaca nemestrina) and related to pregnancy outcome. For 22 weeks, behavioral data were collected from nine breeding groups, consisting of zero to one male (some males were removed after a cycle of conceptions for husbandry reasons) and four to eight females. Observations included all occurrences of 11 aggressive behaviors during 15 min observation sessions, 1-3 times a week. Mean weekly aggression levels during the study period were determined for each group as well as for each pregnancy. Aggression data were summarized with Principal Components Analyses. Results indicate that pigtailed macaque aggression falls into five distinctive categories: warn, engage, threaten, pursue, and attack. Breeding groups differed in their levels of aggression, even after controlling for group size, presence of a sire, and group stability. Levels of the five aggression categories were found to affect the probability that a pregnancy ended in either a natural birth of a live infant, a clinical intervention producing a live infant, or a nonviable outcome. The predictive value of aggression was significant when clinical interventions were included as possible reproductive outcomes. Behavioral observation of captive groups could identify "risk" conditions affecting pregnancy outcome and the requirement for clinical intervention.

Floating limb behaviors and self-biting are associated in laboratory monkeys.

Early descriptions of floating limb behaviors in monkeys were associated with isolation rearing, a practice that ended more than two decades ago. The present authors named various forms of behaviors in which a leg is elevated for no apparent reason: "Floating Limb Suite" (FLS). Floating limb behaviors, identified in laboratory monkeys at the Washington National Primate Research Center (WaNPRC), consist of two subcategories distinguished by whether monkeys seem to react to the elevated leg or ignore it. Given the past association of isolation rearing with both self-biting (SB) and floating limb, the investigators predicted that SB and FLS would be associated in monkeys not reared in isolation. The investigators tracked, over a period of 3 years, the presence of FLS and SB in macaques (Macaca nemestrina, M. fascicularis, M. mulatta) and Papio cynocephalus at WaNPRC. SB and both subcategories of FLS occurred in mother-reared and surrogate-peer-nursery-reared monkeys. We analyzed presence of FLS, the two subcategories of FLS, and SB in 1,117 macaques monitored for up to 3 years, and 781 macaques observed for 8 min of structured data collection. The Papio sample size was insufficient for statistical analysis. Both sampling methodologies found FLS and FLS subcategories to be associated with SB. Nearly half the monkeys only engaging in seemingly harmless nonreactive forms of FLS also performed the potentially injurious behavior of self-biting. The positive association between FLS and SB suggests that monkeys exhibiting one of these behaviors are at a heightened risk for developing the other. One impediment to studying floating limb behaviors is lack of consensus on definitions. This study defined seven forms of apparently functionless elevated limb behaviors. Continued research on factors associated with floating limb behaviors across demographic groups and settings may provide insights into the etiology and treatment of self-biting.

Puppy Temperament Assessments Predict Breed and American Kennel Club Group but Not Adult Temperament.

Puppy assessments for companion dogs have shown mixed long-term reliability. Temperament is cited among the reasons for surrendering dogs to shelters. A puppy temperament test that reliably predicts adult behavior is one potential way to lower the number of dogs given to shelters. This study used a longitudinal design to assess temperament in puppies from 8 different breeds at 7 weeks old (n = 52) and 6 years old (n = 34) using modified temperament tests, physiological measures, and a follow-up questionnaire. For 7-week-old puppies, results revealed (a) puppy breed was predictable using 3 variables, (b) 4 American Kennel Club breed groups had some validity based on temperament, (c) temperament was variable within litters of puppies, and (d) certain measures of temperament were related to physiological measures (heart rate). Finally, puppy temperament assessments were reliable in predicting the scores of 2 of the 8 adult dog temperament measures. However, overall, the puppy temperament scores were unreliable in predicting adult temperament.

The effects of visitor density and intensity on the behavior of two captive jaguars (Panthera onca).

Several researchers have reported significant effects of visitor density and intensity on captive animal behavior. This study determined whether this was the case for 2 captive jaguars housed at the Woodland Park Zoo, Seattle, WA. Subjects were monitored for changes in behavior as a function of visitor density and intensity. The jaguars were observed for 8 hr per week for 29 weeks--March 31 until October 11, 1998--for a total of 230 hr. Continuous frequency sampling was used, and visitor density and intensity were recorded every minute. Parametric statistics were used to test for correlations between behavior and density, intensity, or a combination of the two. Both density and intensity were significant for time spent non-visible for both cats, and intensity showed a significant effect on the female's pacing behavior. In addition, the male cat exhibited a trend for increased aggression based on both visitor density and intensity and a trend of intensity affecting his social behavior. In conclusion, both density and intensity had a significant effect on behavior, with intensity showing a larger effect.

The effects of automated scatter feeders on captive grizzly bear activity budgets.

Although captive bears are popular zoo attractions, they are known to exhibit high levels of repetitive behaviors (RBs). These behaviors have also made them particularly popular subjects for welfare research. To date, most research on ursid welfare has focused on various feeding methods that seek to increase time spent searching for, extracting, or consuming food. Prior research indicates an average of a 50% reduction in RBs when attempts are successful and, roughly, a 50% success rate across studies. This research focused on decreasing time spent in an RB while increasing the time spent active by increasing time spent searching for, extracting, and consuming food. The utility of timed, automated scatter feeders was examined for use with captive grizzly bears (Ursis arctos horribilis). Findings include a significant decrease in time spent in RB and a significant increase in time spent active while the feeders were in use. Further, the bears exhibited a wider range of behaviors and a greater use of their enclosure.

Tenure in current captive setting and age predict personality changes in adult pigtailed macaques.

Personality change in nonhuman primates is a topic that warrants more research attention. Many studies focus on intraindividual repeatability, but few note population-wide trends in personality change. In part, this results from the large sample size that is required to detect such trends. In the present study, we measured personality in a large sample (N = 293) of adult, mother-reared pigtailed macaques, Macaca nemestrinam, over a period of 3 years. We looked at four personality components (sociability towards humans, cautiousness, aggressiveness and fearfulness) derived from behavioural observations at two to four time points per subject. We found these components to have repeatabilities similar to those reported elsewhere in the literature. We then analysed population-wide changes in personality components over time using a linear mixed effects model with three predictors: entry age at the current primate facility, tenure at the primate facility at the time of the first personality test and time elapsed since the first personality test. We found that adult personality changed with life experiences (here, tenure at the facility where tested) and age. Throughout adulthood, pigtailed macaques became less cautious and more aggressive. At the same time, subjects became less cautious and more sociable with increasing time in individual caging at the current primate research facility. We also found that individuals differed significantly in their personality consistency. Other researchers may benefit by applying similar methodology to that described here as they extrapolate about personality measures over time.

Thromboelastography values from pigtail macaques ( Macaca nemestrina): effects of age and sex.

Thromboelastography is a clinical laboratory test used to assess global hemostasis. With technologic advances and the test's reemergence in human medicine, its utility in veterinary medicine is being explored. Because assays for PT, aPTT, and d-dimers require platelet-poor plasma, whereas thromboelastography is performed on whole blood, thromboelastography provides a more accurate representation of coagulation and allows the identification of hypocoagulable, hypercoagulable, and hyperfibrinolytic states. Conflicting information has been reported about the effects of age and sex on thromboelastog- raphy in humans and animals. Human studies have reported significant effects of age and sex on thromboelastography more often than have animal studies, but few publications are available about thromboelastography in the nonhuman primate and laboratory animal literature. We used a sample of 50 pigtail macaques (Macaca nemestrina) to determine whether age or sex influence thromboelastography values. Of 5 measured and 2 calculated variables produced by thromboelastography, sex had a significant effect only on the lysis-30 parameter, which also showed significant interaction between age and sex; values increased with age in male macaques but decreased with age in female macaques. In addition, we used the data to define reference intervals for thromboelastography parameters in pigtail macaques.

Two-item discrimination and Hamilton search learning in infant pigtailed macaque monkeys.

This study investigated how infant pigtailed macaque monkeys performed on two separate learning assessments, two-object discrimination/reversal and Hamilton search learning. Although the learning tasks have been tested on several species, including non-human primates, there have been no normative results reported for young macaque monkeys. The present study provides normative results for these learning tasks in very young captive pigtailed macaques and investigates the degree to which performances on these assessments are related. In addition, an error analysis was conducted to understand the choice patterns of the animals on each task. It was found that males took longer to reach criterion than females on the two-object reversal task. Performance and latency on the discrimination task predicted performance and latency on the reversal task. Performance on Hamilton Search Set-Breaking negatively predicted performance on the later Hamilton Search Forced Set-Breaking task. Finally, latency on reversal significantly predicted the latency on the Hamilton search task. These data provide strong evidence of a relationship between performance on discrimination and reversal. This study shows that, otherwise, each task assesses a different cognitive function.

Risk factors for dystocia in pigtailed macaques (Macaca nemestrina).

Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources.

MR imaging of the brain in fat embolism syndrome.

Fat embolism syndrome (FES) is an uncommon but serious complication of traumatic injury and is frequently diagnostically challenging. In this paper, the authors present four patients who sustained lower extremity long bone injury and who had a normal Glasgow Coma Scale before orthopedic surgical intervention. However, postoperatively, significant neurological deterioration developed in these patients. While cranial computed tomography (CT) obtained immediately after surgery for acutely altered mental status was negative in two of the four patients, brain magnetic resonance imaging (MRI) demonstrated white and gray matter abnormalities accounting for the impaired neurological status in all cases. MRI findings in conjunction with clinical presentation established the diagnosis in all patients. MRI is indicated in any patient with orthopedic injuries who manifests an unexplained acute alteration in mental status, despite a normal head CT.

Genetics and caging type affect birth weight in captive pigtailed macaques (Macaca nemestrina).

The heritability of birth weight was estimated in 3,562 captive pigtailed macaques using 30 years of breeding and pedigree records. Based on a pedigree of over 12,000 animals, quantitative genetic analyses were performed using statistical variance decomposition methods. The model included additive genetic effects, cytoplasmic genetic effects, birth environment, shared maternal environment, and unmeasured environmental effects. The results demonstrated a strong (h(2) = 0.51) heritable component of birth weight overall, and included significant additive genetic heritability (h(2) = 0.23), and cytoplasmic heritability (h(2) = 0.09). In addition, a significant effect of birth location and cage type was identified, explaining an additional 6% of birth weight variance. The use of a nonhuman primate model for studying the effects of genes on birth weight eliminated many of the problems associated with confounding variables in human studies, and allowed for the quantification of a heritable component of birth weight.