Pleiotropy in the melanocortin system: expression levels of this system are associated with melanogenesis and pigmentation in the tawny owl (Strix aluco)

The adaptive function of melanin‐based coloration is a long‐standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin‐based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce α‐melanin‐stimulating hormone (α‐MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while α‐MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin‐based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology.     

Utility of the NavX® Electroanatomic Mapping System for Permanent Pacemaker Implantation in a Pregnant Patient with Chagas Disease

Chagas disease is a highly prevalent zoonosis in Mexico, Central, and South America. Early cardiac involvement is one of the most serious complications of this disease, and conduction disturbances may occur at an early age. We describe a young pregnant woman with Chagas disease and a high degree atrioventricular block, who required implantation of a permanent dual chamber pacemaker. Using an electroanatomic navigation EnSite NavX® system the pacemaker was successfully implanted with minimal fluoroscopic exposure. This case demonstrates the safety and feasibility of using an electroanatomic navigation system to guide permanent pacemaker implantation minimizing x-ray exposure in pregnant patients.     

Alarm scent-marking during predatory attempts in the Cabrera vole (Microtus cabrerae Thomas, 1906)

The alarm pheromones often released by animals under stressful situations seem to elicit behavioral changes in conspecifics, which in the appropriate context can be viewed as anti-predatory responses. However, the releasing of alarm pheromones associated with predatory events has not been demonstrated in mammals. In the current study with wild-caught Cabrera voles, we carried out experiments in the laboratory and in the field to assess the release of alarm pheromones in scent-marks during simulated predatory events and disclose their effects on conspecifics. We first conducted an assay wherein voles where let to scent-mark a clean substrate in the absence of disturbance (control) and under the simulation of predatory events. Contrarily to the control, no fecal boli were released and the area marked with urine was significantly larger during the predatory simulation. In a subsequent assay, we assessed the voles’ preference between urine-marks released under predatory simulation and in control conditions. Voles showed a significant preference by control substrates. Finally, a third assay was carried out in the vole’s habitat wherein the individual activity was monitored by radio-tracking before and after placement of urine-marks obtained during the conditions described above. The vole’s activity was only reduced near the urine-marks released during the simulated predatory events. The results suggest that: (1) during predatory attempts, Cabrera voles release an alarm pheromone in their urine-marks; (2) the putative alarm pheromone reduces the voles’ activity in the surroundings of the marked area; (3) the putative alarm pheromone persists in the field affecting conspecifics’ activity for several days.     

Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

Background

Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress.

Results

We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved.

Conclusions

Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.

     

A distinctive fungal community inhabiting cryoconite holes on glaciers in Svalbard

Cryoconite holes on glacier surfaces are ice-cold hot spots of microbial diversity and activity but still little is known about their fungal inhabitants. We provide the first report of distinctive fungal communities in cryoconite debris from three valley glaciers at Kongsfjorden, Svalbard. Multivariate analysis of terminal-restriction fragment length polymorphism (T-RFLP) profiles of rRNA ITS amplicons revealed that quite distinct fungal communities were found in cryoconite holes compared with soils from adjacent moraine and tundra sites, and that communities on glaciers with contrasting ice-surface hydrology also differed. Most of the fungi cultured from cryoconite sediment were basidiomycetous yeasts or filamentous Ascomycota (Helotiales/Pleosporales). The latter included aeroaquatic fungi, such as Articulospora and Varicosporium, implying a role for these important freshwater decomposers in the carbon dynamics of cryoconite holes. Matching of the dominant peaks from T-RFLP analysis to predicted peaks of cultured isolates confirmed the abundance of these aeroaquatic fungi but also revealed that most of the dominant T-RFLP peaks did not match any cultured isolates. Considering the prevalence and endangerment of glacial environments worldwide, these findings would suggest that their potential as reservoirs of fungal diversity should not be overlooked.     

Nosocomial Bloodstream Infections in Brazilian Pediatric Patients: Microbiology,Epidemiology, and Clinical Features

Background

Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients.

Methods

We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project).

Results

In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients (≤16 years of age). Ninety-six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a pediatric or neonatal intensive-care unit (ICU). The most frequent underlying conditions were malignancy, in 95 patients (27.8%). Among the potential factors predisposing patients to BSI, central venous catheters were the most frequent (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%, respectively, were resistant to imipenem.

Conclusions

In our multicenter study, we found a high mortality and a large proportion of gram-negative bacilli with elevated levels of resistance in pediatric patients.     

Deficiency of C5L2 Increases Macrophage Infiltration and Alters Adipose Tissue Function in Mice

Background

Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT) of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP), and C5a, involved in innate immunity.

Aim

We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl) and C5L2 knock-out (C5L2^−/−) mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO) conditions.

Results

In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold) both over time and with DIO. By contrast, in C5L2^−/−, there was no change in C5aR in WAT. C5L2^−/− mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro-) vs M2 (anti-inflammatory) macrophage proportion was unchanged but C5L2^−/− adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2^−/− mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2^−/− mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance.

Conclusion

Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.