Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome

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Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function

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Specific and selective peptide-membrane interactions revealed using quartz crystal microbalance

The skin secretions of Australian tree frogs are rich in peptides with potential antimicrobial activity. They interrupt bacterial cell membranes, although precisely how and whether all peptides have the same mechanism is not known. The interactions of three of these peptides—aurein 1.2, maculatin 1.1, and caerin 1.1 with supported phospholipid bilayers—are examined here using quartz crystal microbalance and atomic force microscopy. These approaches enabled us to reveal variations in material structure and density as a function of distance from the sensor surface when comparing mass sensorgrams over a range of harmonics of the natural resonance of the sensor crystal and hence obtain for the first time to our knowledge a mechanistic assessment of membrane disruption. We found that caerin inserted into the bilayer in a transmembrane manner, regardless of concentration and phospholipid composition consistent with a pore-forming mechanism. In contrast, maculatin and aurein interacted with membranes in a concentration-dependent manner. At low concentrations (<5 μM), maculatin exhibited transmembrane incorporation whereas aurein was limited to surface association. Upon reaching a threshold value of concentration, both peptides lysed the membrane. In the case of maculatin, the lysis progressed in a slow, concentration-dependent manner, forming mixed micelles, as shown by atomic force microscopy imaging. Aurein-induced lysis proceeded to a sudden disruption, which is consistent with the “carpet” mechanism. Both maculatin and aurein exhibit specificity toward phospholipids and thus have potential as candidates as antimicrobial drugs.     

Urban birds have broader environmental tolerance

Urbanization dramatically changes the composition and diversity of biotic communities. The characteristics distinguishing species that persist in urban environments, however, are poorly understood. Here we test the hypothesis that broadly adapted organisms are better able to tolerate urbanization, using a phylogenetically controlled, global comparison of birds. We compared elevational and latitudinal distributions of 217 urban birds found in 73 of the world's largest cities with distributions of 247 rural congeners to test the hypothesis that urban birds possess broader environmental tolerance. Urban birds had markedly broader environmental tolerance than rural congeners, as estimated by elevational and latitudinal distributions. Our results suggest that broad environmental tolerance may predispose some birds to thrive in urban habitats. The mechanisms mediating such environmental tolerance warrant further investigation, but probably include greater behavioural, physiological and ecological flexibility.     

Genetic structure of endangered lake chubsucker Erimyzon sucetta in Canada reveals a differentiated population in a precarious habitat

We used mitochondrial DNA to assess the genetic structure of endangered lake chubsucker Erimyzon sucetta across its Canadian range. We found unique mitochondrial haplotypes in Lyons Creek, a tributary of the Niagara River that faces a strong potential for habitat deterioration. Lyons Creek may therefore serve as a reservoir of unique genetic diversity. The sensitivity of Lyons Creek, combined with the genetic uniqueness of its E. sucetta population, call for further investigation into whether this population should be considered a separate designatable unit for conservation purposes.     

SIRT6 stabilization and cytoplasmic localization in macrophages regulates acute and chronic inflammation in mice

Acute and chronic inflammations are key homeostatic events in health and disease. Sirtuins (SIRTs), a family of NAD-dependent protein deacylases, play a pivotal role in the regulation of these inflammatory responses. Indeed, SIRTs have anti-inflammatory effects through a myriad of signaling cascades, including histone deacetylation and gene silencing, p65/RelA deacetylation and inactivation, and nucleotide‑binding oligomerization domain, leucine rich repeat, and pyrin domain‑containing protein 3 inflammasome inhibition. Nevertheless, recent findings show that SIRTs, specifically SIRT6, are also necessary for mounting an active inflammatory response in macrophages. SIRT6 has been shown to positively regulate tumor necrosis factor alpha (TNFα) secretion by demyristoylating pro-TNFα in the cytoplasm. However, how SIRT6, a nuclear chromatin-binding protein, fulfills this function in the cytoplasm is currently unknown. Herein, we show by Western blot and immunofluorescence that in macrophages and fibroblasts there is a subpopulation of SIRT6 that is highly unstable and quickly degraded via the proteasome. Upon lipopolysaccharide stimulation in Raw 264.7, bone marrow, and peritoneal macrophages, this population of SIRT6 is rapidly stabilized and localizes in the cytoplasm, specifically in the vicinity of the endoplasmic reticulum, promoting TNFα secretion. Furthermore, we also found that acute SIRT6 inhibition dampens TNFα secretion both in vitro and in vivo, decreasing lipopolysaccharide-induced septic shock. Finally, we tested SIRT6 relevance in systemic inflammation using an obesity-induced chronic inflammatory in vivo model, where TNFα plays a key role, and we show that short-term genetic deletion of SIRT6 in macrophages of obese mice ameliorated systemic inflammation and hyperglycemia, suggesting that SIRT6 plays an active role in inflammation-mediated glucose intolerance during obesity.     

Mechanisms of biodiversity between Campylobacter sequence types in a flock of broiler–breeder chickens

Commercial poultry flocks frequently harbor the dangerous bacterial pathogen Campylobacter. As exclusion efforts frequently fail, there is interest in potential ecologically informed solutions. A long‐term study of Campylobacter sequence types was used to investigate the competitive framework of the Campylobacter metacommunity and understand how multiple sequence types simultaneously co‐occur in a flock of chickens. A combination of matrix and patch‐occupancy models was used to estimate parameters describing the competition, transmission, and mortality of each sequence type. It was found that Campylobacter sequence types form a strong hierarchical framework within a flock of chickens and occupied a broad spectrum of transmission–mortality trade‐offs. Upon further investigation of how biodiversity is thus maintained within the flock, it was found that the demographic capabilities of Campylobacter, such as mortality and transmission, could not explain the broad biodiversity of sequence types seen, suggesting that external factors such as host‐bird health and seasonality are important elements in maintaining biodiversity of Campylobacter sequence types.     

Sampling multiple life stages significantly increases estimates of marine biodiversity

Biodiversity assessments are critical for setting conservation priorities, understanding ecosystem function and establishing a baseline to monitor change. Surveys of marine biodiversity that rely almost entirely on sampling adult organisms underestimate diversity because they tend to be limited to habitat types and individuals that can be easily surveyed. Many marine animals have planktonic larvae that can be sampled from the water column at shallow depths. This life stage often is overlooked in surveys but can be used to relatively rapidly document diversity, especially for the many species that are rare or live cryptically as adults. Using DNA barcode data from samples of nemertean worms collected in three biogeographical regions—Northeastern Pacific, the Caribbean Sea and Eastern Tropical Pacific—we found that most species were collected as either benthic adults or planktonic larvae but seldom in both stages. Randomization tests show that this deficit of operational taxonomic units collected as both adults and larvae is extremely unlikely if larvae and adults were drawn from the same pool of species. This effect persists even in well-studied faunas. These results suggest that sampling planktonic larvae offers access to a different subset of species and thus significantly increases estimates of biodiversity compared to sampling adults alone. Spanish abstract is available in the electronic supplementary material.