Palmitoylation-induced Aggregation of Cysteine-string Protein Mutants That Cause Neuronal Ceroid Lipofuscinosis

Recently, mutations in the DNAJC5 gene encoding cysteine-string protein α (CSPα) were identified to cause the neurodegenerative disorder adult-onset neuronal ceroid lipofuscinosis. The disease-causing mutations (L115R or ΔL116) occur within the cysteine-string domain, a region of the protein that is post-translationally modified by extensive palmitoylation. Here we demonstrate that L115R and ΔL116 mutant proteins are mistargeted in neuroendocrine cells and form SDS-resistant aggregates, concordant with the properties of other mutant proteins linked to neurodegenerative disorders. The mutant aggregates are membrane-associated and incorporate palmitate. Indeed, co-expression of palmitoyltransferase enzymes promoted the aggregation of the CSPα mutants, and chemical depalmitoylation solubilized the aggregates, demonstrating that aggregation is induced and maintained by palmitoylation. In agreement with these observations, SDS-resistant CSPα aggregates were present in brain samples from patients carrying the L115R mutation and were depleted by chemical depalmitoylation. In summary, this study identifies a novel interplay between genetic mutations and palmitoylation in driving aggregation of CSPα mutant proteins. We propose that this palmitoylation-induced aggregation of mutant CSPα proteins may underlie the development of adult-onset neuronal ceroid lipofuscinosis in affected families.     

Meningeal worm is a long-lived parasitic nematode in white-tailed deer

A natural infection of the meningeal worm, Parelaphostrongylus tenuis, persisted for at least 3.7 yr in a white-tailed deer (Odocoileus virginianus). The deer was 5-7 yr old and was shedding dorsal-spined nematode larvae at the time of quarantine. Larvae were extracted from all fecal samples collected up to 730 days post-quarantine (dpq) and thereafter only at 862 dpq and at necropsy (1,350 dpq). Live adults of P. tenuis, one male and one female, were recovered from the cranium at necropsy. Parelaphostrongylus tenuis infections are long lived and latent periods may be extended. Our findings reaffirm the need for reliable antemortem diagnosis to identify non-patent P. tenuis infections to prevent inadvertent introduction of infected animals to non-endemic areas.     

Effects of cold stress and exercise on fat loss in females

A Latin Square design has been used to test the responses of 24 relatively fit young women to 200 minute bouts of exercise performed over 5 day trials under each of three different ambient conditions: 15 degrees C (warm-warm; (WW)); -20 degrees C while inhaling, from a facemask, air heated to 18 degrees C (cold-warm; (CW)); and -20 degrees C (cold-cold; (CC)). In both of the cold environments, special clothing and boots were provided (insulation 0.47 degree C X watt-1 X m-2 and 0.62 degree C X watt-1 X m-2; (4 and 3 CLO units)). All three trials led to a small (0.6-0.7 degree C) rise of rectal temperature, but in the two cold environments mean body temperatures fell by over 1.0 degree C. A large increase of serum ketones occurred under all conditions, and the exercise respiratory quotient suggested some increase of fat utilization, WW (0.85) through CW (0.84) to CC (0.83). A fat loss of about 0.5 kg over the five days was confirmed by hydrostatic weighing and measurement of skinfold thicknesses. This was much less than the change previously observed in men, and moreover, it seemed to be independent of ambient conditions. Possible reasons why cold did not increase fat loss in these women include: a lower relative intensity of exercise; a greater stability of fat stores in women; avoidance of caffeine; a possible translocation of subcutaneous fat to deep fat depots; and a greater desire to "lose weight" irrespective of environmental conditions.     

The ageing mitochondrial genome

The population of elderly individuals has increased significantly over the past century and is predicted to rise even more rapidly in the future. Ageing is a major risk factor for many diseases such as neurodegenerative disease, diabetes and cancer. This highlights the importance of understanding the mechanisms involved in the ageing process. One plausible mechanism for ageing is accumulation of mutations in the mitochondrial genome. In this review, we discuss some of the most convincing data surrounding age-related mtDNA mutations and the evidence that these mutations contribute to the ageing process.     

Biocontrol of Amaranthus spp. in Europe: state of the art

Within European COST Action 816, a 5-year collaboration between scientists from 6 European countries has made an important contribution to the previously unstudied insect fauna associated with Amaranthus spp. in Europe. This provides a basis for future introductions of a non-native biocontrol agent into Europe. In addition, two promising microbial herbicides, based on the fungi Alternaria alternata and Trematophoma lignicola have been characterised. Further work on their use in integrated farming systems is required. The use of microbial herbicides in conjunction with new cropping systems, such as green cover crops or living mulch using Trifolium subterraneum is an approach which offers much potential.     

A model to explain the posterior limit of the bite point in reptiles.

A biomechanical model of the jaw mechanism in some reptiles is presented. Symmetrical muscle activity that produces equal forces on both sides of the head is assumed. The model predicts the position of the most posterior bit point and offers a functional explanation for this prediction. Turtles are used to illustrate the idea.     

Mobility and Navigation among the Yucatec Maya

Sex differences in range size and navigation are widely reported, with males traveling farther than females, being less spatially anxious, and in many studies navigating more effectively. One explanation holds that these differences are the result of sexual selection, with larger ranges conferring mating benefits on males, while another explanation focuses on greater parenting costs that large ranges impose on reproductive-aged females. We evaluated these arguments with data from a community of highly monogamous Maya farmers. Maya men and women do not differ in distance traveled over the region during the mate-seeking years, suggesting that mating competition does not affect range size in this monogamous population. However, men’s regional and daily travel increases after marriage, apparently in pursuit of resources that benefit families, whereas women reduce their daily travel after marriage. This suggests that parental effort is more important than mating effort in this population. Despite the relatively modest overall sex difference in mobility, Maya men were less spatially anxious than women, thought themselves to be better navigators, and pointed more accurately to distant locations. A structural equation model showed that the sex by marital status interaction had a direct effect on mobility, with a weaker indirect effect of sex on mobility mediated by navigational ability.