Assessment of mirror image facial asymmetries in monozygotic and dizygotic twins

Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2015 (Department of Orthodontics and Dentofacial Orthopedics).Includes bibliographic references: leaves 43-50.Background: Mirror imaging in identical twins has long been noted and suggests that left-right asymmetry may become established early in embryogenesis. However, it is not known whether the clinical reports of “mirroring” in twins are annulled by an equal number of cases lacking mirroring. As left-right patterning is a key component of laterality-based birth defects, it is important to determine whether aspects of left-right asymmetry are in fact set prior to the splitting event that produces monozygotic twins. We aimed to determine whether significant mirror imaging occurs in transverse facial asymmetries in monozygotic and dizygotic twins. Material and Methods: The sample included PA cephalograns from 56 pairs of monozygotic twins and 57 pairs of dizygotic twins from the Forysth/Moorrees Twin Study (females age 14-1 5 and males age 15-16). The films were digitized and anatomical landmarks identified. Using Geometric Morphometric analyses including Procrustes superimposition, the landmark configuration of one individual twin was reflected (mirrored) and superimposed using Procrustes superimposition. Principal components analysis (PCA) and MANOVA tests 1V were performed to determine the differences between monozygotic and dizygotic twins. A secondary Procrustes superimposition was then conducted without reflection. If mirroring asymmetry was present, the average Procrustes distance within reflected twin sets (D1) would be smaller than those superimposed without reflection (D2). T tests were performed to determine the differences between reflected and non-reflected regions in monozygotic and dizygotic twins. Results: After reflection, no statistically significant differences were found for any regions (with the exception of Mandible A Right, p=0.0258) between monozygotic and dizygotic twins. When comparing reflected versus non-reflected regions, Midface D Left and Mandible C Right in dizygotic twins yielded negative values for D1-D2; however permutation tests revealed these values are not significant. T tests showed 15 out of 20 regions had significant smaller mean values for D2 versus Dl in monozygotic twins, while only 7 out of 20 in dizygotic. A Z test comparing these two proportions revealed this difference between twin types is significant (p=0.011), With the monozygotic twins having significantly more regions that fit better when non-reflected than the dizygotic twins. Conclusion: No statistically significant differences in mirroring were found between monozygotic and dizygotic twins in any craniofacial regions except for Mandible A Right, in which dizygotic twins showed a better fit when mirrored. Upon examination of the differences between reflected and non-reflected regions, monozygotic twins showed a statistically significantly greater number of regions that fit better when superimposed versus reflected in comparison to dizygotic twins. From this study we conclude that no significant mirroring occurs in craniofacial asymmetries, perhaps due to the biological stability of neural crest cells that derive the cranial cartilage and skeleton

Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions

Objectives: Changes in subchondral bone (SCB) and cross-talk with articular cartilage (AC) have been linked to osteoarthritis (OA). Using micro-computed tomography (micro-CT) this study: (1) examines changes in SCB architecture in a non-invasive loading mouse model in which focal AC lesions are induced selectively in the lateral femur, and (2) determines any modifications in the contralateral knee, linked to changes in gait, which might complicate use of this limb as an internal control. Methods: Right knee joints of CBA mice were loaded: once with 2weeks of habitual use (n=7), for 2weeks (n=8) or for 5weeks (n=5). Both left (contralateral) and right (loaded) knees were micro-CT scanned and the SCB and trabecular bone analysed. Gait analysis was also performed. Results: These analyses showed a significant increase in SCB thickness in the lateral compartments in joints loaded for 5weeks, which was most marked in the lateral femur; the contralateral non-loaded knee also showed transient SCB thickening (loaded once and repetitively). Epiphyseal trabecular bone BV/TV and trabecular thickness were also increased in the lateral compartments after 5 weeks of loading, and in all joint compartments in the contralateral knee. Gait analysis showed that applied loading only affected gait in the contralateral himd-limb in all groups of mice from the second week after the first loading episode. Conclusions: These data indicate a spatial link between SCB thickening and AC lesions following mechanical trauma, and the clear limitations associated with the use of contralateral joints as controls in such OA models, and perhaps in OA diagnosis

Sexually dimorphic tibia shape is linked to natural osteoarthritis in STR/Ort mice

Human osteoarthritis (OA) is detected only at late stages. Male STR/Ort mice develop knee OA spontaneously with known longitudinal trajectory, offering scope to identify OA predisposing factors. We exploit the lack of overt OA in female STR/Ort and in both sexes of parental, control CBA mice to explore whether early divergence in tibial bone mass or shape are linked to emergent OA

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Rabies post-exposure prophylaxis started during or after travel: a GeoSentinel analysis

Background Recent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5–20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel. Methodology/Principal findings We conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014–July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12–0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0–1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99–11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5–157.2; P = 0.01), were more likely to receive RIG in the country of exposure. Conclusions/Significance This analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention

Better Few than Hungry: Flexible Feeding Ecology of Collared Lemurs Eulemur collaris in Littoral Forest Fragments

Frugivorous primates are known to encounter many problems to cope with habitat degradation, due to the fluctuating spatial and temporal distribution of their food resources. Since lemur communities evolved strategies to deal with periods of food scarcity, these primates are expected to be naturally adapted to fluctuating ecological conditions and to tolerate a certain degree of habitat changes. However, behavioral and ecological strategies adopted by frugivorous lemurs to survive in secondary habitats have been little investigated. Here, we compared the behavioral ecology of collared lemurs (Eulemur collaris) in a degraded fragment of littoral forest of south-east Madagascar, Mandena, with that of their conspecifics in a more intact habitat, Sainte Luce.Lemur groups in Mandena and in Sainte Luce were censused in 2004/2007 and in 2000, respectively. Data were collected via instantaneous sampling on five lemur groups totaling 1,698 observation hours. The Shannon index was used to determine dietary diversity and nutritional analyses were conducted to assess food quality. All feeding trees were identified and measured, and ranging areas determined via the minimum convex polygon. In the degraded area lemurs were able to modify several aspects of their feeding strategies by decreasing group size and by increasing feeding time, ranging areas, and number of feeding trees. The above strategies were apparently able to counteract a clear reduction in both food quality and size of feeding trees.Our findings indicate that collared lemurs in littoral forest fragments modified their behavior to cope with the pressures of fluctuating resource availability. The observed flexibility is likely to be an adaptation to Malagasy rainforests, which are known to undergo periods of fruit scarcity and low productivity. These results should be carefully considered when relocating lemurs or when selecting suitable areas for their conservation