The role of self-compassion in the psychological (mal)adjustment of older adults: a scoping review.

BACKGROUND: The identification of protection factors regarding older adults' mental health is essential. Self-compassion, the capacity to be kind towards the self during challenging times, may be one such factor. Although still scarce, some research in this field has already been conducted with older adults. Our research question was the following: what is currently known about the role of self-compassion in the psychological (mal)adjustment of older adults? OBJECTIVES: To review any study designs, in any setting, where self-compassion and any indicators of psychological (mal)adjustment were assessed in participants aged ≥60 years. DESIGN: A scoping review of English, Portuguese, and Spanish published and unpublished materials, using the EBSCOhost Research and PubMed databases and reference lists. Search terms included self-compassion, self compassion, older adults, elderly, seniors, and geriatrics. After screening and selection of the studies, we charted the relevant data. RESULTS: Eleven published studies (2012-2018) were reviewed. Self-compassion was associated with, and a predictor of, diverse mental health indicators in older adults. Self-compassion was also associated with indicators of physical health, moderated the relationship between physical health indicators and mental health indicators, and mediated the relationship between diverse mental health indicators. Results were obtained with participants of different nationalities and age. All studies had a cross-sectional design, and most studies recruited well-functioning community residents. CONCLUSIONS: Self-compassion is beneficial for the psychological adjustment of older adults and may also benefit their biological functioning. Self-compassion seems particularly relevant for those experiencing more negative life events. Studies with more robust methodologies are needed in order to replicate these findings.

Rich but random: parasite communities of snouted treefrog, Scinax fuscovarius (Anura: Hylidae), in Bodoquena Mountains, western Brazil.

Hosts represent discrete habitats that contain finite parasite communities, and individual hosts can be used as replicates in parasitism studies, such as investigations of the processes that mediate the formation of parasite communities. However, within a single host population, there may be singularities among individuals that affect parasite contact rates. Accordingly, the goals of the present study were to document the parasites associated with the small treefrog Scinax fuscovarius, to verify possible variation and co-occurrences in parasite infracommunities, and to assess the effects of host characteristics (size and sex) on infracommunity structure. Treefrog specimens (n = 75) were collected from the Bodoquena Mountains in Mato Grosso do Sul, Brazil. After collection, the specimens were transported to the laboratory, and examined for parasitic. The parasites found were removed, fixed, and identified. Patterns in parasite infracommunity organization were analyzed using the checkerboard score index, which was calculated using a presence-absence matrix. The matrix was randomized under the null hypothesis that the infracommunities independently represent the component community. Forty-two (56%) of the individuals harbored at least one parasite, and a total of 500 metazoan parasites were recovered, with a particularly rich composite community of 18 taxa, including 13 nematodes, two trematodes, one cestode, one oligochaete, and one mite larvae. The parasite species were randomly distributed among the infracommunities, with no evidence of co-occurrence, segregation, or aggregation. However, both body size and sex influenced infection, with larger hosts harboring more parasites and parasites were more abundant in male specimens and more species rich in female specimens. These results suggest that the parasite infracommunities of S. fuscovarius are shaped by both random factors and individual host characteristics.

Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer).

Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

Height patterning of nanostructured surfaces with a focused helium ion beam: a precise and gentle non-sputtering method.

This work presents a new technique for surface patterning with focused ion beams. The technique is based on chemical decomposition in the bulk of a polymer substrate with negligible surface sputtering effects. By using a focused helium ion beam, generated in a helium ion microscope, we show that the surface height of polymethyl methacrylate substrates can be patterned with nanometer depth precision, while preserving the essential features of the nanostructures prefabricated on this surface. The key factors that control this patterning process are discussed.

Effect of glycerol feed-supplementation on seabass metabolism and gut microbiota.

Dietary glycerol supplementation in aquaculture feed is seen as an alternative and inexpensive way to fuel fish metabolism, attenuate metabolic utilization of dietary proteins and, subsequently, reduce nitrogen excretion. In this study, we evaluated the impact of dietary glycerol supplementation on nitrogen excretion of European seabass (Dicentrarchus labrax) and its effects on metabolite profile and bacterial community composition of gut digesta. These effects were evaluated in a 60-day trial with fish fed diets supplemented with 2.5% or 5% (w/w) refined glycerol and without glycerol supplementation. Nuclear magnetic resonance spectroscopy and high-throughput 16S rRNA gene sequencing were used to characterize the effects of glycerol supplementation on digesta metabolite and bacterial community composition of 6-h postprandial fish. Our results showed that ammonia excretion was not altered by dietary glycerol supplementation, and the highest glycerol dosage was associated with significant increases in amino acids and a decrease of ergogenic creatine in digesta metabolome. Concomitantly, significant decreases in putative amino acid degradation pathways were detected in the predicted metagenome analysis, suggesting a metabolic shift. Taxon-specific analysis revealed significant increases in abundance of some specific genera (e.g., Burkholderia and Vibrio) and bacterial diversity. Overall, our results indicate glycerol supplementation may decrease amino acid catabolism without adversely affecting fish gut bacterial communities.Key points• Glycerol can be an inexpensive and energetic alternative in fish feed formulations.• Glycerol did not affect nitrogen excretion and gut bacteriome composition.• Glycerol reduced uptake of amino acids and increased uptake of ergogenic creatine.• Glycerol reduced putative amino acid degradation pathways in predicted metagenome.

Canine parvovirus: a predicting canine model for sepsis.

BACKGROUND: Sepsis is a severe condition associated with high prevalence and mortality rates. Parvovirus enteritis is a predisposing factor for sepsis, as it promotes intestinal bacterial translocation and severe immunosuppression. This makes dogs infected by parvovirus a suitable study population as far as sepsis is concerned. The main objective of the present study was to evaluate the differences between two sets of SIRS (Systemic Inflammatory Response Syndrome) criteria in outcome prediction: SIRS 1991 and SIRS 2001. The possibility of stratifying and classifying septic dogs was assessed using a proposed animal adapted PIRO (Predisposition, Infection, Response and Organ dysfunction) scoring system. RESULTS: The 72 dogs enrolled in this study were scored for each of the PIRO elements, except for Infection, as all were considered to have the same infection score, and subjected to two sets of SIRS criteria, in order to measure their correlation with the outcome. Concerning SIRS criteria, it was found that the proposed alterations on SIRS 2001 (capillary refill time or mucous membrane colour alteration) were significantly associated with the outcome (OR = 4.09, p < 0.05), contrasting with the 1991 SIRS criteria (p = 0.352) that did not correlate with the outcome. No significant statistical association was found between Predisposition (p = 1), Response (p = 0.1135), Organ dysfunction (p = 0.1135), total PIRO score (p = 0.093) and outcome. To explore the possibility of using the SIRS criteria as a fast decision-making tool, a Fast-and-Frugal tree (FFT) was created with a sensitivity of 92% and a specificity of 29%. CONCLUSION: These results suggest that increasing the SIRS criteria specificity may improve their prognostic value and their clinical usefulness. In order to improve the proposed PIRO scoring system outcome prediction ability, more specific criteria should be added, mainly inflammatory and organ dysfunction biomarkers.

Diaphanocephalus galeatus (Nematoda: Diaphanocephalidae), a poorly known parasite of lizards: redescription, first genetic characterization and a revision of its congeners from Brazil.

Diaphanocephalus galeatus collected from the small intestine of the lizard Dracaena paraguayensis in the Pantanal wetlands, State of Mato Grosso do Sul, Brazil, is redescribed. Genetic characterization and observations using scanning electron microscopy (SEM) were performed for the first time. The vouchers of D. galeatus and the type specimens of its congeners, deposited in the Coleção Helmintológica do Instituto Oswaldo Cruz (CHIOC), were consulted. Light and SEM observations revealed several undescribed features of D. galeatus, i.e. structure of the cephalic end and of the buccal capsule, position and morphology of deirids, presence of phasmids in females and presence of unpaired papilla on the membranous projection that covers the genital cone in males. After observation of the specimens deposited in the helminthological collection, D. jacuruxi is considered a synonym of D. galeatus, and D. diesingi, despite its incomplete description, is tentatively retained as valid due to the poor condition of the type material. The results also indicated low host specificity of D. galeatus, contradicting previous assertions. Genetic comparisons using patristic distances and phylogenetic trees generated from sequences of the 28S rRNA nuclear gene indicated that D. galeatus is closer to the taxa within Ancylostomatoidea and Strongyloidea than any lineage of Metastrongyloidea or Trichostrongyloidea. However, most of the nodal supports were low. Based on the genetic and morphological characterization, the validity of D. galeatus was confirmed. These data may serve for further comparative approaches for different populations of the parasite, from different hosts in different geographical areas, mitigating taxonomic confusions.

A new species of Raphidascaris (Nematoda: Raphidascarididae) infecting the fish Gymnogeophagus balzanii (Cichlidae) from the Pantanal wetlands, Brazil and a taxonomic update of the subgenera of Raphidascaris based on molecular phylogeny and morphology.

Raphidascaris (Sprentascaris) andersoni n. sp. (Nematoda: Raphidascarididae) collected in the intestine of the humphead cichlid Gymnogeophagus balzanii (Perugia) from the Pantanal wetlands, State of Mato Grosso do Sul (Brazil) is described and genetically characterized. The new species differs from its congeners mainly by having a conspicuous papilla-like formation slightly anterior to the cloacal aperture. Furthermore, males of R. (S.) lanfrediae and R. (S.) mahnerti have caudal alae, and R. (S.) hypostomi and R. (S.) pimelodi lack lateral alae, whereas in the new species caudal alae are absent and lateral alae present. The remaining congeners, namely, R. (S.) marano and R. (S.) saltaensis differ from Raphidascaris (Sprentascaris) andersoni n. sp. mainly because males have three pairs of postcloacal papillae (vs five pairs). In the phylogenetic reconstructions, using three nuclear genetic markers (18S, ITS1-5.8S-ITS2 and 28S rDNA) and one mitochondrial (cox1 mtDNA), the new species was separated from other representatives of Raphidascarididae, and the absence of monophyly in Hysterothylacium and Raphidascaroides was confirmed. Moreover, the subgenera Sprentascaris and Ichthyascaris appeared to be monophyletic. Therefore, even though Raphidascaris (Raphidascaris) was apparently not monophyletic, the subgenera of Raphidascaris should be re-erected as valid genera. The updated diagnoses of Ichthyascaris, Raphidascaris and Sprentascaris are given. The present study represents the first parasitological survey in G. balzanii.

Anuran helminth communities from contrasting nature reserve and pasture sites in the Pantanal wetland, Brazil.

Studies of amphibian macroparasites are relevant for the investigation of parasite community ecology and disease dynamics. Here, the parasite communities of five anuran species (Hypsiboas raniceps, Phyllomeduza azurea, Pseudis paradoxa, Leptodactylus fuscus and Leptodactylus podicipinus) are described from two habitats with different levels of preservation (pasture versus nature reserve). Specifically, we used mixed-effect models to test whether helminth species richness, prevalence and abundance differ between the two host collection sites. A total of 120 anuran individuals and 25 helminth parasite taxa were collected. Helminth communities differed between collection sites and among host species. In general, helminth species richness, prevalence and abundance were higher in hosts collected in the pond from the nature reserve. In all, these data help fill the gap in parasite biodiversity knowledge in a changing area, within a sensitive group of vertebrate hosts.

Functional morphology of the tetra fish Astyanax lacustris differs between divergent habitats in the Pantanal wetlands.

This study investigated whether the body morphology of the tetra fish Astyanax lacustris (previously Astyanax asuncionensis) varied between populations inhabiting one lagoon (a lentic, shallow environment, with great habitat complexity created by aquatic macrophytes) and an adjacent river (a deeper, lotic environment where aquatic macrophytes are scarce) in a seasonally flooded wetland, despite population mixing during the wet season. Morphological differences matched a priori predictions of the theory relating functional body morphology and swimming performance in fishes between lagoon and river habitats. Observed morphological variation could have resulted from adaptive habitat choice by tetras, predation by piscivores and adaptive phenotypic plasticity during development.

Benzofuroxan derivatives N-Br and N-I induce intrinsic apoptosis in melanoma cells by regulating AKT/BIM signaling and display anti metastatic activity in vivo.

BACKGROUND: Malignant melanoma is an aggressive type of skin cancer, and despite recent advances in treatment, the survival rate of the metastatic form remains low. Nifuroxazide analogues are drugs based on the substitution of the nitrofuran group by benzofuroxan, in view of the pharmacophore similarity of the nitro group, improving bioavailability, with higher intrinsic activity and less toxicity. Benzofuroxan activity involves the intracellular production of free-radical species. In the present work, we evaluated the antitumor effects of different benzofuroxan derivatives in a murine melanoma model. METHODS: B16F10-Nex2 melanoma cells were used to investigate the antitumor effects of Benzofuroxan derivatives in vitro and in a syngeneic melanoma model in C57Bl/6 mice. Cytotoxicity, morphological changes and reactive oxygen species (ROS) were assessed by a diphenyltetrasolium reagent, optical and fluorescence microscopy, respectively. Annexin-V binding and mitochondrial integrity were analyzed by flow cytometry. Western blotting and colorimetry identified cell signaling proteins. RESULTS: Benzofuroxan N-Br and N-I derivatives were active against murine and human tumor cell lines, exerting significant protection against metastatic melanoma in a syngeneic model. N-Br and N-I induce apoptosis in melanoma cells, evidenced by specific morphological changes, DNA condensation and degradation, and phosphatidylserine translocation in the plasma membrane. The intrinsic mitochondrial pathway in B16F10-Nex2 cells is suggested owing to reduced outer membrane potential in mitochondria, followed by caspase -9, -3 activation and cleavage of PARP. The cytotoxicity of N-Br and N-I in B16F10-Nex2 cells is mediated by the generation of ROS, inhibited by pre-incubation of the cells with N-acetylcysteine (NAC). The induction of ROS by N-Br and N-I resulted in the inhibition of AKT activation, an important molecule related to tumor cell survival, followed by upregulation of BIM. CONCLUSION: We conclude that N-Br and N-I are promising agents aiming at cancer treatment. They may be useful in melanoma therapy as inducers of intrinsic apoptosis and by exerting significant antitumor activity against metastatic melanoma, as presently shown in syngeneic mice.

Diversity and patterns of interaction of an anuran-parasite network in a neotropical wetland.

We describe the diversity and structure of a host-parasite network of 11 anuran species and their helminth parasites in the Pantanal wetland, Brazil. Specifically, we investigate how the heterogeneous use of space by hosts changes parasite community diversity, and how the local pool of parasites exploits sympatric host species of different habits. We examined 229 anuran specimens, interacting with 32 helminth parasite taxa. Mixed effect models indicated the influence of anuran body size, but not habit, as a determinant of parasite species richness. Variation in parasite taxonomic diversity, however, was not significantly correlated with host size or habit. Parasite community composition was not correlated with host phylogeny, indicating no strong effect of the evolutionary relationships among anurans on the similarities in their parasite communities. Host-parasite network showed a nested and non-modular pattern of interaction, which is probably a result of the low host specificity observed for most helminths in this study. Overall, we found host body size was important in determining parasite community richness, whereas low parasite specificity was important to network structure.

Positive impact of dietary water on in vivo epidermal water physiology.

BACKGROUND/PURPOSE: The importance of water in human physiology is well known, also for skin functionality. This study was conducted to assess the effects of dietary water on epidermal skin hydration in healthy females. METHODS: Thirty-four healthy females (mean 24.5 ± 6.34 years old) were selected and characterized according to their dietary daily habits, by a previously validated Food Frequency Questionnaire. For 1 month, these subjects were asked to add 2 L/day of water to their regular dietary habits. Measurements took place at day D0, D15, and D30, and involved general variables (body weight, blood pressure, Body Mass Index) and specific skin physiological variables in five anatomical sites (ventral forearm, anterior leg, dorsal hand, zygomatic area, and forehead) involving epidermal superficial and deep hydration, by capacitance and transepidermal water loss (TEWL). RESULTS: This water overload (2 L/day/30 days) did not change the blood volume or weight of the individuals. However, both superficial and deep skin hydration were clearly in those individuals that regularly consumed lees water per day. No significant effect was observed in the TEWL. CONCLUSIONS: This study clearly suggests that dietary water intake seems to influence skin water content. Nevertheless further in vivo investigations involving other variables, such as biomechanical descriptors, should follow to look deeper into this aspect of skin physiology.

Cytomegalovirus Identification in Blood and Urine of Newborns by Nested Polymerase Chain Reaction.

AIM: To study the frequency of congenital cytomegalovirus (CMV) infection in newborns admitted to the Division of Neonatology, using nested polymerase chain reaction (PCR) and DNA to detect differences in blood and urine specimens. METHODS: The study was carried out for eight months. Newborns (n = 520) hospitalized in five hospitals in Campo Grande, Mato Grosso do Sul, Brazil, were checked for CMV by analysing blood and urine samples. RESULTS: Cytomegalovirus was PCR positive in 13 urine and 10 blood samples. Of the 13 positive urine patients, three (23%) had no clinical signs suggestive of CMV, and another three (23%) patients admitted to the neonatal intensive care unit (NICU) had no definite findings of bacterial infection, with negative blood culture and some clinical signs consistent with CMV as cholestasis, hepatomegaly and eosinophilia. Three patients were on mechanical ventilation and showed improvement after prescription of ganciclovir. One CMV positive child progressed to death. CONCLUSION: Cytomegalovirus detection in urine was slightly more efficient than in blood, and showed better sensitivity than in serological analysis (p < 0.01) therefore, boiled urine may be a better and easier specimen tool for CMV diagnosis in neonatal infection. The findings of the present research suggest that patients admitted to the NICU, especially premature infants, whose laboratory results are not compatible with bacterial infection, and exhibiting signs suggestive of CMV infection should have PCR done on urine for confirmation.

Biofilm-formation by Staphylococcus aureus and Staphylococcus epidermidis isolates from subclinical mastitis in conditions mimicking the udder environment.

Staphylococcus is the genus most commonly isolated from bovine mastitis in many countries. It may express several virulence factors including biofilm formation, which may protect the bacterial community from antimicrobials' action, preventing these compounds from reaching its interior, where they reach subinhibitory concentrations (subMIC). Most biofilm production assays are performed in static conditions, while studies regarding antimicrobial resistance usually do not resemble the udder environment because they are performed at high concentrations. In this study we evaluated the influence of dynamic conditions and media, including Mueller Hinton Broth (MHB) and UHT whole milk (WM), as well as the effect of subMIC concentrations of five different antimicrobial agents on biofilm formation by staphylococci isolated from subclinical mastitis. Results suggest that dynamic conditions and media may influence biofilm formation and revealed that milking simulation may significantly increase biofilm production. Sub-MIC concentrations decrease biofilm formation in MHB but increase in WM, suggesting a protective role of milk against antimicrobial compounds' action. Therefore, in vitro conditions that simulate the udder environment and in vivo conditions should be included as one of the parameters in evaluation of biofilm producing strains, in order to provide more reliable results.

Effect of simulated gastrointestinal conditions on biofilm formation by Salmonella 1,4,[5],12:i:-.

Salmonella Typhimurium 1,4,[5],12:i:- is a major serovar responsible for human salmonellosis whose biofilm-forming ability, influenced by environmental conditions like those found in the gastrointestinal tract, is one of the main contributing factors to its ability to persist in the host and thus one of the main causes of chronic relapsing infections. Most studies to evaluate biofilm formation are performed in microtiter assays using standard media. However, no reports are available on the ability of this serovar to produce biofilm under in vitro simulated gastrointestinal conditions which better correlate with the environment found in the gastrointestinal tract. To address this, a modified biofilm assay simulating intestinal fluid was conceived to assess the biofilm formation of 133 Salmonella Typhimurium 1,4,[5],12:i:- isolates with and without agitation and at three different time points (24 h, 48 h, and 72 h). The results were then compared to the existing microtiter method using conventional biofilm growth medium (Mueller Hinton Broth). Statistical analysis revealed significant differences in the results obtained between the three protocols used. The simulated human intestinal environment impaired biofilm production demonstrating that conditions like pH, agitation or the presence of enzymes can influence biofilm production. Therefore, results from in vitro simulation of in vivo conditions may contribute to unravelling factors relating to biofilm formation and persistence in the context of the human host.

Variation in the parasite community of the sardine fish Triportheus nematurus (Actinopterygii: Characidae) from the Medalha lagoon in the Pantanal wetland, Brazil.

In July 2009 and July 2010 (two dry periods separated by an atypically large flood in the Pantanal wetland of Brazil), 34 and 33 specimens of the sardine fish Triportheus nematurus were collected, respectively, for the study of the metazoan parasite community of this species. Parasite ecological and community descriptors were calculated for both host samples, and possible similarities were tested statistically. Five species of metazoan parasites were identified, four of which were common to both host samples. A total of 61 metazoan parasites were collected from all fish hosts (17 specimens in July 2009 (mean: 0.5 ± 0.66 parasites/fish) and 44 specimens in July 2010 (mean: 1.33 ± 1.41 parasites/fish)). The nematode Procamallanus hilarii and the monogenean Anacanthorus sp. were the most prevalent and abundant species in 2009 and 2010, respectively. The mean total abundance and species richness were significantly higher in 2010. Parasite communities in both samples of T. nematurus were characterized by species with low prevalence, abundance, mean total abundance and species richness, thus indicating low parasite diversity. Significant differences in the prevalence and abundance of P. hilarii and Anacanthorus sp. between the two samples allowed the discrimination of infracommunities, which were united in two distinct groups. This appears to be the first evidence that the peculiar hydrological dynamics of the southern Pantanal wetland (Brazil) exert an important influence over the structure of the parasite community.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes.

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases.

Innate stimulation of B1a cells enhances the autoreactive IgM repertoire in the NOD mouse: implications for type 1 diabetes.

AIMS/HYPOTHESIS: We sought to determine whether the presence of natural autoreactive antibodies of B1a cell origin would play a role in the initiation of type 1 diabetes. METHODS: We compared IgM repertoires and B1a cell compartments in NOD and C57BL/6 mice. Serum IgM autoreactivity profiles were determined by ELISA and the secretory properties and activation status of B1a cells were characterised by enzyme-linked immunosorbent spot (ELISPOT) assay and flow cytometry. B1a cell response to innate activation was analysed by gene expression assays, ELISA and [(3)H]thymidine incorporation. The effect of NOD IgM produced by B1a cells on NOD.severe combined immunodeficient (SCID) beta cells was examined in co-cultures: IgM binding was measured by flow cytometry and real-time PCR was used to study oxidative stress responses. RESULTS: NOD mice displayed increased levels of serum anti-insulin IgM that were independent of the H2 locus, that were maintained up to prediabetic stages and that correlated with the NOD B1a cell secretion profile. NOD B1a cells had a naturally increased pattern of activation, expressed higher levels of toll-like-receptors (Tlrs) and responded to TLR stimulation in vitro with higher proliferation and increased capacity to secrete anti-type-1-diabetes-related IgM, but produced lower amounts of IL10. IgM of NOD B1a cell origin was able to bind to pancreatic beta cells in vitro and induce expression of inducible nitric oxide synthase (Nos2). CONCLUSIONS/INTERPRETATION: NOD B1a cells had a lower innate activation threshold for secretion of autoreactive IgM capable of triggering oxidative stress responses on binding to pancreatic beta cells; this provides an early mechanism that contributes to diabetes in a mouse model of type 1 diabetes.

Global phylogeography and evolution of chelonid fibropapilloma-associated herpesvirus.

A global phylogeny for chelonid fibropapilloma-associated herpesvirus (CFPHV), the most likely aetiological agent of fibropapillomatosis (FP) in sea turtles, was inferred, using dated sequences, through Bayesian Markov chain Monte Carlo analysis and used to estimate the virus evolutionary rate independent of the evolution of the host, and to resolve the phylogenetic positions of new haplotypes from Puerto Rico and the Gulf of Guinea. Four phylogeographical groups were identified: eastern Pacific, western Atlantic/eastern Caribbean, mid-west Pacific and Atlantic. The latter comprises the Gulf of Guinea and Puerto Rico, suggesting recent virus gene flow between these two regions. One virus haplotype from Florida remained elusive, representing either an independent lineage sharing a common ancestor with all other identified virus variants or an Atlantic representative of the lineage giving rise to the eastern Pacific group. The virus evolutionary rate ranged from 1.62×10(-4) to 2.22×10(-4) substitutions per site per year, which is much faster than what is expected for a herpesvirus. The mean time for the most recent common ancestor of the modern virus variants was estimated at 192.90-429.71 years ago, which, although more recent than previous estimates, still supports an interpretation that the global FP pandemic is not the result of a recent acquisition of a virulence mutation(s). The phylogeographical pattern obtained seems partially to reflect sea turtle movements, whereas altered environments appear to be implicated in current FP outbreaks and in the modern evolutionary history of CFPHV.