Brain immune cells undergo cGAS-STING-dependent apoptosis during herpes simplex virus type 1 infection

Protection of the brain from viral infections involves the type I interferon (IFN-I) system, defects in which renders humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels leads to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we here show that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, while lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices, or mice treated with caspase inhibitor, exhibited lower viral load and improved outcome of infection. Collectively, we identify an activation-induced apoptosis program in brain immune cells which down-modulates local immune responses

Orofacial manifestations in outpatients with anorexia nervosa and bulimia nervosa focusing on the vomiting behavior

Objective: This case-control study aims to evaluate the oral health status and orofacial problems in a group of outpatients with eating disorders (ED)—either anorexia nervosa (AN) or bulimia nervosa (BN)—further focusing on the influence of vomit. Materials and methods: Fifty-five women outpatients with AN or BN diagnosis were invited to participate, of which 33 agreed. ED outpatients and matched controls were submitted to a questionnaire and clinical oral examination. Results: Multivariate analysis identified a significantly higher incidence of teeth-related complications (i.e., tooth decay, dental erosion, and self-reported dentin hypersensitivity), periodontal disease, salivary alterations (i.e., hyposalivation and xerostomia), and oral mucosa-related complications in ED outpatients. Dental erosion, self-reported dentin hypersensitivity, hyposalivation, xerostomia, and angular cheilitis were found to be highly correlated with the vomiting behavior. Conclusions: ED outpatients were found to present a higher incidence of oral-related complications and an inferior oral health status, compared to gender- and age-matched controls. Alterations verified within outpatients were acknowledged to be quite similar to those previously reported within inpatients, in both of nature and severity, thus sustaining that the cranio-maxillofacial region is significantly affected by ED, even in the early/milder forms of the condition, as expectedly verified within outpatients.The work was supported by the Faculty of Dental Medicine, U. Porto

Trends in popularity of some morphological traits of purebred dogs in Australia.

Background The morphology of dogs can provide information about their predisposition to some disorders. For example, larger breeds are predisposed to hip dysplasia and many neoplastic diseases. Therefore, longitudinal trends in popularity of dog morphology can reveal potential disease pervasiveness in the future. There have been reports on the popularity of particular breeds and behavioural traits but trends in the morphological traits of preferred breeds have not been studied. Methods This study investigated trends in the height, dog size and head shape (cephalic index) of Australian purebred dogs. One hundred eighty-one breeds derived from Australian National Kennel Council (ANKC) registration statistics from 1986 to 2013 were analysed. Weighted regression analyses were conducted to examine trends in the traits by using them as outcome variables, with year as the explanatory variable and numbers of registered dogs as weights. Linear regression investigated dog height and cephalic index (skull width/skull length), and multinomial logistic regression studied dog size. Results The total number of ANKC registration had decreased gradually from 95,792 in 1986 to 66,902 in 2013. Both weighted minimal height (p = 0.014) and weighted maximal height (p < 0.001) decreased significantly over time, and the weighted cephalic index increased significantly (p < 0.001). The odds of registration of medium and small breeds increased by 5.3 % and 4.2 %, respectively, relative to large breeds (p < 0.001) and by 12.1 % and 11.0 %, respectively, relative to giant breeds (p < 0.001) for each 5-year block of time. Conclusions Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Mean cephalic index has increased, which indicates that Australians have gradually favoured breeds with shorter and wider heads (brachycephalic). These significant trends indicate that the dog morphological traits reported here may potentially influence how people select companion dogs in Australia and provide valuable predictive information on the pervasiveness of diseases in dogs. Keywords: Purebred dogs, Dog popularity, Dog height, Dog size, Cephalic index, Brachycephalic Disease, predisposition, Australia. Plain English Summary Some diseases in dogs are related to certain physical characteristics. For example, larger breeds have a higher risk of getting hip dysplasia and certain neoplastic diseases while breeds with wider and shorter heads, such as Pug and French bulldog, are more likely to experience breathing problems and dystocia. Therefore, if we know the trends in popularity of dogs of a certain morphology, we may be able to predict disease pervasiveness. The study aimed to investigate the trends in the height, dog size and head shape of Australian purebred dogs. The numbers of dogs registered within the 181 breeds in Australian National Kennel Council (ANKC) every year from 1986 to 2013 were obtained and analysed. The total number of ANKC registration had decreased from 95,792 in 1986 to 66,902 in 2013. Compared to taller and larger breeds, shorter and smaller breeds have become relatively popular over time. Also, the data suggest that Australians increasingly favour dogs with shorter and wider heads for whose welfare veterinarians often express concern [1, 2]. The results indicate that dog height, dog size and dog head shape may potentially influence how people select companion dogs in Australia and provide valuable predictive information on trends in disease prevalence, enabling the veterinary profession and industry to prepare for potential future caseloads

Selenomethionine Incorporation into Amyloid Sequences Regulates Fibrillogenesis and Toxicity

The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties

Abdominal obesity and metabolic syndrome: exercise as medicine?

Background: Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. Purpose of this review: This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. Conclusion: There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome

Stable carbon and nitrogen isotope enrichment in primate tissues

Isotopic studies of wild primates have used a wide range of tissues to infer diet and model the foraging ecologies of extinct species. The use of mismatched tissues for such comparisons can be problematic because differences in amino acid compositions can lead to small isotopic differences between tissues. Additionally, physiological and dietary differences among primate species could lead to variable offsets between apatite carbonate and collagen. To improve our understanding of the isotopic chemistry of primates, we explored the apparent enrichment (ε*) between bone collagen and muscle, collagen and fur or hair keratin, muscle and keratin, and collagen and bone carbonate across the primate order. We found that the mean ε* values of proteinaceous tissues were small (≤1‰), and uncorrelated with body size or phylogenetic relatedness. Additionally, ε* values did not vary by habitat, sex, age, or manner of death. The mean ε* value between bone carbonate and collagen (5.6 ± 1.2‰) was consistent with values reported for omnivorous mammals consuming monoisotopic diets. These primate-specific apparent enrichment values will be a valuable tool for cross-species comparisons. Additionally, they will facilitate dietary comparisons between living and fossil primates

Rhamnolipids: diversity of structures, microbial origins and roles

Rhamnolipids are glycolipidic biosurfactants produced by various bacterial species. They were initially found as exoproducts of the opportunistic pathogen Pseudomonas aeruginosa and described as a mixture of four congeners: α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-Rha-C10-C10), α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoate (Rha-Rha-C10), as well as their mono-rhamnolipid congeners Rha-C10-C10 and Rha-C10. The development of more sensitive analytical techniques has lead to the further discovery of a wide diversity of rhamnolipid congeners and homologues (about 60) that are produced at different concentrations by various Pseudomonas species and by bacteria belonging to other families, classes, or even phyla. For example, various Burkholderia species have been shown to produce rhamnolipids that have longer alkyl chains than those produced by P. aeruginosa. In P. aeruginosa, three genes, carried on two distinct operons, code for the enzymes responsible for the final steps of rhamnolipid synthesis: one operon carries the rhlAB genes and the other rhlC. Genes highly similar to rhlA, rhlB, and rhlC have also been found in various Burkholderia species but grouped within one putative operon, and they have been shown to be required for rhamnolipid production as well. The exact physiological function of these secondary metabolites is still unclear. Most identified activities are derived from the surface activity, wetting ability, detergency, and other amphipathic-related properties of these molecules. Indeed, rhamnolipids promote the uptake and biodegradation of poorly soluble substrates, act as immune modulators and virulence factors, have antimicrobial activities, and are involved in surface motility and in bacterial biofilm development