Interplay Between Weight Loss and Gut Microbiota Composition in Overweight Adolescents

The aim of this study was to determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents. Thirty‐six adolescents (13–15 years), classified as overweight according to the International Obesity Task Force BMI criteria, were submitted to a calorie‐restricted diet (10–40%) and increased physical activity (15–23 kcal/kg body weight/week) program over 10 weeks. Gut bacterial groups were analyzed by quantitative real‐time PCR before and after the intervention. A group of subjects (n = 23) experienced >4.0 kg weight loss and showed significant BMI (P = 0.030) and BMI z‐score (P = 0.035) reductions after the intervention, while the other group (n = 13) showed <2.0 kg weight loss. No significant differences in dietary intake were found between both groups. In the whole adolescent population, the intervention led to increased Bacteroides fragilis group (P = 0.001) and Lactobacillus group (P = 0.030) counts, and to decreased Clostridium coccoides group (P = 0.028), Bifidobacterium longum (P = 0.031), and Bifidobacterium adolescentis (P = 0.044) counts. In the high weight–loss group, B. fragilis group and Lactobacillus group counts also increased (P = 0.001 and P = 0.007, respectively), whereas C. coccoides group and B. longum counts decreased (P = 0.001 and P = 0.044, respectively) after the intervention. Total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts were significantly higher (P < 0.001–0.036) while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum were significantly lower (P < 0.001–0.008) in the high weight–loss group than in the low weight–loss group before and after the intervention. These findings indicate that calorie restriction and physical activity have an impact on gut microbiota composition related to body weight loss, which also seem to be influenced by the individual's microbiota.     

Molecular Mechanisms of Paraptosis Induction: Implications for a Non-Genetically Modified Tumor Vaccine

Paraptosis is the programmed cell death pathway that leads to cellular necrosis. Previously, rodent and human monocytes/macrophages killed glioma cells bearing the membrane macrophage colony stimulating factor (mM-CSF) through paraptosis, but the molecular mechanism of this killing process was never identified. We have demonstrated that paraptosis of rat T9 glioma cells can be initiated through a large potassium channel (BK)-dependent process initiated by reactive oxygen species. Macrophage mediated cytotoxicity upon the mM-CSF expressing T9-C2 cells was not prevented by the addition of the caspase inhibitor, zVAD-fmk. By a combination of fluorescent confocal and electron microscopy, flow cytometry, electrophysiology, pharmacology, and genetic knock-down approaches, we demonstrated that these ion channels control cellular swelling and vacuolization of rat T9 glioma cells. Cell lysis is preceded by a depletion of intracellular ATP. Six-hour exposure to BK channel activation caused T9 cells to over express heat shock proteins (Hsp 60, 70, 90 and gp96). This same treatment forced HMGB1 translocation from the nuclear region to the periphery. These last molecules are “danger signals” that can stimulate immune responses. Similar inductions of mitochondrial swelling and increased Hsp70 and 90 expressions by BK channel activation were observed with the non-immunogenic F98 glioma cells. Rats injected with T9 cells which were killed by prolonged BK channel activation developed immunity against the T9 cells, while the injection of x-irradiated apoptotic T9 cells failed to produce the vaccinating effect. These results are the first to show that glioma cellular death induced by prolonged BK channel activation improves tumor immunogenicity; this treatment reproduces the vaccinating effects of mM-CSF transduced cells. Elucidation of strategies as described in this study may prove quite valuable in the development of clinical immunotherapy against cancer.     

Pre-fledging survival in a Yellow-legged Gull Larus michahellis population in northern Iberia is mostly determined by hatching date

Capsule: Pre-fledging survival in a Yellow-legged Gull Larus michahellis population in northern Iberia is negatively correlated to hatching date.

Aims: To explore which factors have more importance in determining the pre-fledging daily survival rates in a Yellow-legged Gull population from northern Iberia. Specifically, we tested for the effect of hatching date and order, body size and condition and meteorological conditions on pre-fledging survival.

Methods: Cormack–Jolly–Seber models with mixtures were used to model daily survival rates.

Results: Daily survival rates were mostly negatively affected by hatching date.

Conclusions: Hatching date was the most important factor affecting survival of chicks during the pre-fledging period in a Yellow-legged Gull colony from northern Iberia.     

Transformations of Some Sesquiterpene Lactones by Filamentous Fungi and Cytotoxic Evaluations

Biotransformation is an economically and ecologically viable technology which has been used to modify the structures of many classes of biologically active products. Some fungi may be useful for the biotransformation of sesquiterpene lactones (SLs), leading to unusual structural changes that modify their biological activities, and other transformations mimic their biosynthetic pathways, generating evidences for the proposed biogenesis. Eight filamentous fungi were screened for their ability to transform different SLs ( 1  –  9 ), and microbial reactions yielded compounds 10  –  17 , which in turn have been isolated as natural products, thus mimicking their biosynthesis. Their structures were identified based on NMR and MS spectroscopic analyses. The cytotoxicities of SLs 1 , 4 , 6 , 7 and 9 , and their biotransformed produts ( 10 , 14 , 15 and 17 ) against human cancer cell lines U251 (glia), PC3 (prostate), K562 (leukemia), HCT‐15 (colon), MCF7 (breast), and SKLU‐1 (lung), were determined, confirming that the presence of Michael acceptor is an important feature for the bioactivity.     

Long‐term monitoring of tropical alpine habitat change,Andean anurans,and chytrid fungus in the Cordillera Vilcanota,Peru: Results from a decade of study

The Cordillera Vilcanota in southern Peru is the second largest glacierized range in the tropics and home to one of the largest high‐alpine lakes, Sibinacocha (4,860 m). Here, Telmatobius marmoratus (marbled water frog), Rhinella spinulosa (Andean toad), and Pleurodema marmoratum (marbled four‐eyed frog) have expanded their range vertically within the past century to inhabit newly formed ponds created by ongoing deglaciation. These anuran populations, geographically among the highest (5,200–5,400 m) recorded globally, are being impacted by the chytrid fungus Batrachochytrium dendrobatidis (Bd), and the disease it causes, chytridiomycosis. In this study, we report results from over a decade of monitoring these three anuran species, their habitat, and Bd infection status. Our observations reveal dynamic changes in habitat including ongoing rapid deglaciation (18.4 m/year widening of a corridor between retreating glaciers from 2005 to 2015), new pond formation, changes in vegetation in amphibian habitat, and widespread occurrence of Bd in amphibians in seven sites. Three of these sites have tested positive for Bd over a 9‐ to 12‐year period. In addition, we observed a widespread reduction in T. marmoratus encounters in the Vilcanota in 2008, 2009, and 2012, while encounters increased in 2013 and 2015. Despite the rapid and dynamic changes in habitat under a warming climate, continued presence of Bd in the environment for over a decade, and a reduction in one of three anuran species, we document that these anurans continue to breed and survive in this high Andean environment. High variability in anuran encounters across sites and plasticity in these populations across habitats, sites, and years are all factors that could favor repopulation postdecline. Preserving the connectivity of wetlands in the Cordillera Vilcanota is therefore essential in ensuring that anurans continue to breed and adapt as climate change continues to reshape the environment.     

Optogenetic switches for light-controlled gene expression in yeast

Light is increasingly recognized as an efficient means of controlling diverse biological processes with high spatiotemporal resolution. Optogenetic switches are molecular devices for regulating light-controlled gene expression, protein localization, signal transduction and protein-protein interactions. Such molecular components have been mainly developed through the use of photoreceptors, which upon light stimulation undergo conformational changes passing to an active state. The current repertoires of optogenetic switches include red, blue and UV-B light photoreceptors and have been implemented in a broad spectrum of biological platforms. In this review, we revisit different optogenetic switches that have been used in diverse biological platforms, with emphasis on those used for light-controlled gene expression in the budding yeast Saccharomyces cerevisiae. The implementation of these switches overcomes the use of traditional chemical inducers, allowing precise control of gene expression at lower costs, without leaving chemical traces, and positively impacting the production of high-value metabolites and heterologous proteins. Additionally, we highlight the potential of utilizing this technology beyond laboratory strains, by optimizing it for use in yeasts tamed for industrial processes. Finally, we discuss how fungal photoreceptors could serve as a source of biological parts for the development of novel optogenetic switches with improved characteristics. Although optogenetic tools have had a strong impact on basic research, their use in applied sciences is still undervalued. Therefore, the invitation for the future is to utilize this technology in biotechnological and industrial settings.