Pleistocene extinctions and recent expansions in an anguid lizard of the genus Pseudopus

Climatic changes during the Pleistocene played an instrumental role in the shaping recent distribution and diversity of the Western Palearctic biota. Range oscillations often lead to allopatric differentiation followed by the establishment of secondary contact zones. As a result, many species are composed of complex networks of phylogenetic lineages with different histories. Pseudopus apodus is the only surviving member of an ancient genus of Western Palearctic anguid lizards (Anguidae) distributed from the Balkans through Anatolia and Caucasus to central Asia. Here, we used mitochondrial and nuclear DNA sequences to reconstruct the evolutionary history of the species in phylogeographic and demographic frameworks. Our analyses revealed three main phylogenetic lineages that diverged during or shortly before the Pleistocene. Two of them more or less correspond to the known subspecies, and their low genetic variability suggests relatively recent dispersal and colonization of vast parts of the range. The third, southern, lineage is more geographically restricted and diversified than the other two. This pattern shows that the Quaternary climatic oscillations presumably caused repeated large‐scale population extinctions of the species, depleting most of its diversity. Only a few refugia located in Anatolia, Levant, and Transcaucasia served as sources for subsequent recolonization to the areas of the recent distribution. This is in contrast to many other Western Palearctic reptiles that survived unfavorable climatic conditions in numerous local refugia and sanctuaries, which resulted in more complex phylogenetic structure.     

The INA complex facilitates assembly of the peripheral stalk of the mitochondrial F1Fo‐ATP synthase

Mitochondrial F₁F_o‐ATP synthase generates the bulk of cellular ATP. This molecular machine assembles from nuclear‐ and mitochondria‐encoded subunits. Whereas chaperones for formation of the matrix‐exposed hexameric F₁‐ATPase core domain have been identified, insight into how the nuclear‐encoded F₁‐domain assembles with the membrane‐embedded F_o‐region is lacking. Here we identified the INA complex (INAC) in the inner membrane of mitochondria as an assembly factor involved in this process. Ina22 and Ina17 are INAC constituents that physically associate with the F₁‐module and peripheral stalk, but not with the assembled F₁F_o‐ATP synthase. Our analyses show that loss of Ina22 and Ina17 specifically impairs formation of the peripheral stalk that connects the catalytic F₁‐module to the membrane embedded F_o‐domain. We conclude that INAC represents a matrix‐exposed inner membrane protein complex that facilitates peripheral stalk assembly and thus promotes a key step in the biogenesis of mitochondrial F₁F_o‐ATP synthase.     

Automatic food intake detection based on swallowing sounds

This paper presents a novel fully automatic food intake detection methodology, an important step toward objective monitoring of ingestive behavior. The aim of such monitoring is to improve our understanding of eating behaviors associated with obesity and eating disorders. The proposed methodology consists of two stages. First, acoustic detection of swallowing instances based on mel-scale Fourier spectrum features and classification using support vector machines is performed. Principal component analysis and a smoothing algorithm are used to improve swallowing detection accuracy. Second, the frequency of swallowing is used as a predictor for detection of food intake episodes. The proposed methodology was tested on data collected from 12 subjects with various degrees of adiposity. Average accuracies of >80% and >75% were obtained for intra-subject and inter-subject models correspondingly with a temporal resolution of 30 s. Results obtained on 44.1 h of data with a total of 7305 swallows show that detection accuracies are comparable for obese and lean subjects. They also suggest feasibility of food intake detection based on swallowing sounds and potential of the proposed methodology for automatic monitoring of ingestive behavior. Based on a wearable non-invasive acoustic sensor the proposed methodology may potentially be used in free-living conditions.     

Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies

In the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from a broad range of cancer types. This compound acts by two distinct mechanisms. First by activating the AMPK pathway induced by a mitochondrial disorder. Second by inhibition of MELK kinase activity, which induces cell cycle arrest and activation of DNA damage repair pathways by p53 and REDD1 activation. All of these mechanisms activate autophagic and apoptotic processes resulting in melanoma cell death. The strong efficacy of CRO15 to reduce the growth of melanoma xenograft sensitive or resistant to BRAF inhibitors opens interesting perspective.Subject terms: Melanoma, Cell death