Chronic Paracoccidioidomycosis of the Intestine as Single Organ Involvement Points to an Alternative Pathogenesis of the Mycosis

Current knowledge on the natural history of paracoccidioidomycosis states that the chronic form of the disease results from reactivation of quiescent foci established years or decades before during the primary lung infection. Once reactivated, the fungi can disseminate to virtually any organ or system. We present herein two chronic paracoccidioidomycosis patients with a single organ involvement that points to an alternative pathogenesis of the mycosis. These patients suggest that the chronic form may also arise from reactivation of foci not confined to the lungs, due to the early dissemination of yeast cells during the primary infection.     

XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species

Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the inter-relationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPC(KD)) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers.     

Association between coffee,tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders

ABSTRACT

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, p = .003 and p = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) (p = .003), and between coffee and sleep duration (p = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.     

Serological Diagnosis of Paracoccidioidomycosis: High Rate of Inter-laboratorial Variability among Medical Mycology Reference Centers

Background

Serological tests have long been established as rapid, simple and inexpensive tools for the diagnosis and follow-up of PCM. However, different protocols and antigen preparations are used and the few attempts to standardize the routine serological methods have not succeeded.

Methodology/Principal findings

We compared the performance of six Brazilian reference centers for serological diagnosis of PCM. Each center provided 30 sera of PCM patients, with positive high, intermediate and low titers, which were defined as the “reference” titers. Each center then applied its own antigen preparation and serological routine test, either semiquantitative double immunodifusion or counterimmmunoelectrophoresis, in the 150 sera from the other five centers blindly as regard to the “reference” titers. Titers were transformed into scores: 0 (negative), 1 (healing titers), 2 (active disease, low titers) and 3 (active disease, high titers) according to each center''s criteria. Major discordances were considered between scores indicating active disease and scores indicating negative or healing titers; such discordance when associated with proper clinical and other laboratorial data, may correspond to different approaches to the patient''s treatment. Surprisingly, all centers exhibited a high rate of “major” discordances with a mean of 31 (20%) discordant scores. Alternatively, when the scores given by one center to their own sera were compared with the scores given to their sera by the remaining five other centers, a high rate of major discordances was also found, with a mean number of 14.8 sera in 30 presenting a discordance with at least one other center. The data also suggest that centers that used CIE and pool of isolates for antigen preparation performed better.

Conclusion

There are inconsistencies among the laboratories that are strong enough to result in conflicting information regarding the patients'' treatment. Renewed efforts should be promoted to improve standardization of the serological diagnosis of PCM.     

Cross-Scale Interactions and the Distribution-Abundance Relationship

Positive interspecific relationships between local abundance and extent of regional distribution are among the most ubiquitous patterns in ecology. Although multiple hypotheses have been proposed, the mechanisms underlying distribution-abundance (d-a) relationships remain poorly understood. We examined the intra- and interspecific distribution-abundance relationships for a metacommunity of 13 amphibian species sampled for 15 consecutive years. Mean density of larvae in occupied ponds was positively related to number of ponds occupied by species; employing the fraction of ponds uniquely available to each species this same relationship sharply decelerates. The latter relationship suggested that more abundant species inhabited most available habitats annually, whereas rarer species were dispersal limited. We inferred the mechanisms responsible for this pattern based on the dynamics of one species, Pseudacris triseriata, which transitioned between a rare, narrowly distributed species to a common, widely distributed species and then back again. Both transitions were presaged by marked changes in mean local densities driven by climatic effects on habitat quality. We identified threshold densities separating these population regime shifts that differed with landscape configuration. Our data suggest that these transitions were caused by strong cross-scale interactions between local resource/niche processes and larger scale metapopulation processes. The patterns we observed have relevance for understanding the mechanisms of interspecific d-a relationships and critical thresholds associated with habitat fragmentation.     

Censusing the mountain gorillas in the Virunga Volcanoes: complete sweep method versus monitoring

The mountain gorillas (Gorilla beringei beringei) of the Virunga Volcanoes Range of Rwanda, Uganda, and the Democratic Republic of Congo are one of the most endangered ape populations in the world. Following a dramatic decline during the 1960s, and relative stability in the 1970s, the population steadily increased during the 1980s. Due to political instability and war, a complete census had not been conducted since 1989. Here we compare the results of a complete census using the ‘sweep method’ conducted in 2003 with those from a monitoring program, to estimate the size and distribution of the gorilla population. A total of 360 gorillas were counted from census measurements and known habituated groups. Based on quantitative assessments of the census accuracy, we calculated that an additional 20 gorillas were not counted, leading to an estimated population of 380 individuals, and a 1.15% annual growth rate since 1989. The Ranger Based Monitoring programme yielded similar results. The encouraging results must be viewed with caution, however, because the growth was concentrated almost entirely in one section of the Virungas. Additionally, the distribution of gorilla groups was negatively correlated with the frequency of human disturbances, which highlights the need to continue strengthening conservation efforts.     

Functional Implication of Dp71 in Osmoregulation and Vascular Permeability of the Retina

Functional alterations of Müller cells, the principal glia of the retina, are an early hallmark of most retina diseases and contribute to their further progression. The molecular mechanisms of these reactive Müller cell alterations, resulting in disturbed retinal homeostasis, remain largely unknown. Here we show that experimental detachment of mouse retina induces mislocation of the inwardly rectifying potassium channels (Kir4.1) and a downregulation of the water channel protein (AQP4) in Müller cells. These alterations are associated with a strong decrease of Dp71, a cytoskeleton protein responsible for the localization and the clustering of Kir4.1 and AQP4. Partial (in detached retinas) or total depletion of Dp71 in Müller cells (in Dp71-null mice) impairs the capability of volume regulation of Müller cells under osmotic stress. The abnormal swelling of Müller cells In Dp71-null mice involves the action of inflammatory mediators. Moreover, we investigated whether the alterations in Müller cells of Dp71-null mice may interfere with their regulatory effect on the blood-retina barrier. In the absence of Dp71, the retinal vascular permeability was increased as compared to the controls. Our results reveal that Dp71 is crucially implicated in the maintenance of potassium homeostasis, in transmembraneous water transport, and in the Müller cell-mediated regulation of retinal vascular permeability. Furthermore, our data provide novel insights into the mechanisms of retinal homeostasis provided by Müller cells under normal and pathological conditions.     

Differential antibody isotype expression to the major Paracoccidioides brasiliensis antigen in juvenile and adult form paracoccidioidomycosis

We investigated the relationship between antibody response to the major Paracoccidioides brasiliensis antigen, a 43-kDa glycoprotein, and the two paracoccidioidomycosis (PCM) clinical presentations, the juvenile and the adult forms. Total immunoglobulin G (IgG), IgG isotypes, and IgA anti-gp43 antibodies were determined by enzyme-linked immunosorbent assay in patients'sera. Juvenile PCM patients had higher (P =.003) IgG anti-gp43 levels than adult form patients. IgG1 subclass levels, however, were comparable between the two clinical forms. Patients with the juvenile form had higher (P <. 001) IgG4, but lower (P =.03) IgG2 levels than patients with the adult form. The IgG4 isotype, regulated by interleukin 4, was found in all juvenile form patients but in only 12% of the adult form patients. In contrast, high levels of the IgG2 isotype, regulated by interferon-gamma, were found in 41% of the adult PCM patients, mainly those with a more benign disease, but in only 12% of the juvenile patients. IgG3 was either absent or detected at low levels. These results demonstrate, for the first time, specific IgG4 antibodies in the humoral immune response of patients with an endemic deep mycosis and suggest that the switch to the IgG subclasses in PCM is regulated by the patients' T-helper subset (Th-1 or Th-2) dominant cytokine profile. A possible role for IgG4 in the immunopathogenesis of the juvenile, more severe form of the disease is discussed. Finally, IgA was found mainly in adult form patients, probably as a result of the chronic mucosal antigenic stimulation characteristic of this form.     

Lizard diversity and agricultural disturbance in a Caribbean forest landscape

Understanding the impact of agriculture on biodiversity is critical for effective conservation management. Our goal was to determine the impact of agricultural disturbance on the lizard fauna of Los Haitises National Park and the surrounding region in the Dominican Republic. This region has a history of extensive agricultural disturbance followed by abrupt abandonment. Abundance and diversity were surveyed in six habitats: relatively undisturbed hilltop (mogote), four habitats disturbed by agriculture (pasture, oil palm plantation, cacao plantation, conuco or home garden), and one forested habitat. Three of these habitats (pasture, cacao plantation, conuco) were also examined at different stages of activity or abandonment. Glue-trap grids were used to sample each habitat. In general, species richness was lower in more heavily or recently disturbed habitats. Richness was lowest in active agricultural habitats where only 54% of the region's lizard species were detected. Notably, agricultural systems differed considerably in their ability to support a diverse lizard assemblage. Abandoned agricultural habitats had slightly higher richness than their active counterparts, but still contained only 69% of the region's species. By contrast, nearly every native species, including several never observed in agriculturally disturbed habitats, were detected on the undisturbed hilltops (mogotes). These mogotes may have served as refugees for species that could not tolerate disturbance when the region was being heavily exploited for agriculture. Overall, our results suggest that the continued protection of the park, and its mogotes in particular, will be required to maintain the region's lizard diversity.