5 research outputs found
Turtle Carapace Anomalies: The Roles of Genetic Diversity and Environment
Background: Phenotypic anomalies are common in wild populations and multiple genetic, biotic and abiotic factors might contribute to their formation. Turtles are excellent models for the study of developmental instability because anomalies are easily detected in the form of malformations, additions, or reductions in the number of scutes or scales. Methodology/Principal Findings: In this study, we integrated field observations, manipulative experiments, and climatic and genetic approaches to investigate the origin of carapace scute anomalies across Iberian populations of the European pond turtle, Emys orbicularis. The proportion of anomalous individuals varied from 3 % to 69 % in local populations, with increasing frequency of anomalies in northern regions. We found no significant effect of climatic and soil moisture, or climatic temperature on the occurrence of anomalies. However, lower genetic diversity and inbreeding were good predictors of the prevalence of scute anomalies among populations. Both decreasing genetic diversity and increasing proportion of anomalous individuals in northern parts of the Iberian distribution may be linked to recolonization events from the Southern Pleistocene refugium. Conclusions/Significance: Overall, our results suggest that developmental instability in turtle carapace formation might be caused, at least in part, by genetic factors, although the influence of environmental factors affecting the developmental stability of turtle carapace cannot be ruled out. Further studies of the effects of environmental factors, pollutants an
Rab GTPase Proteins in Tauopathy (5236)
Objective: To elucidate the role of specific Rab GTPase proteins, Rab8a or Rab35, in tau accumulation and aggregate formation.
Background: Alzheimer disease (AD) is characterized by the abnormal deposition of amyloid-beta (Aβ) plaques and tau tangles in neurons and glia. Although Aβ correlates well with disease, abnormal, tau accumulation is thought to be a major factor contributing to neurodegeneration in AD. Increasing data indicate that that specific Rab proteins malfunction in affected brain regions in AD. Nearly 70 Rab GTPase proteins have been identified in humans. Rab proteins play an important role in intracellular trafficking, endocytosis, and exocytosis/secretion; and may contribute to clearance of abnormally aggregated proteins including tau. Altered Rab function may be a precursor to tau protein accumulation, aggregation, and associated AD and AD-related pathology. Among several Rab proteins, both Rab8a and Rab35 have emerging roles in Parkinson disease (PD) and AD pathophysiology. In PD Rab35 levels are high in serum and in brain regions affected by disease, implying a role in disease pathology.
Design/Methods: Human neuroglioma H4 cells were co-transfected with 4R0N wild type or self-aggregating mutant tau[P301L/S320F] and Rab8a/35 (and functional mutants). Total tau pathological phospho-tau levels were analyzed by Western blot, and aggregate formation with ThioS. The results were compared to a proteomics dataset and Rab expression analyses in postmortem tissue from from AD, PSP (progressive supranuclear palsy) and CBD (corticobasal degeneration).
Results: In contrast to PD, Rab35 expression is decreased in postmortem brain tissues from AD, PSP and CBD, whereas Rab8a appears increased, especially in white mater. Both Rab8a and Rab35 overexpression in H4 cells resulted in a marked reduction of total and phosphor-tau. Further, Rab8a and Rab35 reduced ThioS positive tau inclusions in vitro.
Conclusions: These data provide the first evidence that Rab8a and Rab35 may regulate tau levels and associated pathology