Family-based treatment of children with severe obesity in a public healthcare setting: Results from a randomized controlled trial

To compare the effectiveness of family-based behavioural social facilitation treatment (FBSFT) versus treatment as usual (TAU) in children with severe obesity. Parallel-design, nonblinded, randomized controlled trial conducted at a Norwegian obesity outpatient clinic. Children aged 6–18 years referred to the clinic between 2014 and 2018 were invited to participate. Participants were randomly allocated using sequentially numbered, opaqued, sealed envelopes. FBSFT (n = 59) entailed 17 sessions of structured cognitive behavioural treatment, TAU (n = 55) entailed standard lifestyle counselling sessions every third month for 1 year. Primary outcomes included changes in body mass index standard deviation score (BMI SDS) and percentage above the International Obesity Task Force cut-off for overweight (%IOTF-25). Secondary outcomes included changes in sleep, physical activity, and eating behaviour. From pre- to posttreatment there was a statistically significant difference in change in both BMI SDS (0.19 units, 95% confidence interval [CI]: 0.10–0.28, p < .001) and %IOTF-25 (5.48%, 95%CI: 2.74–8.22, p < .001) between FBSFT and TAU groups. FBSFT participants achieved significant reductions in mean BMI SDS (0.16 units, (95%CI: −0.22 to −0.10, p < .001) and %IOTF-25 (6.53%, 95% CI: −8.45 to −4.60, p < .001), whereas in TAU nonsignificant changes were observed in BMI SDS (0.03 units, 95% CI: −0.03 to 0.09, p = .30) and %IOTF-25 (−1.04%, 95% CI: −2.99 to −0.90, p = .29). More FBSFT participants (31.5%) had clinically meaningful BMI SDS reductions of ≥0.25 from pre- to posttreatment than in TAU (13.0%, p = .021). Regarding secondary outcomes, only changes in sleep timing differed significantly between groups. FBSFT improved weight-related outcomes compared to TAU.publishedVersio

Neural Correlates of Behavioural Olfactory Sensitivity Changes Seasonally in European Starlings

Possibly due to the small size of the olfactory bulb (OB) as compared to rodents, it was generally believed that songbirds lack a well-developed sense of smell. This belief was recently revised by several studies showing that various bird species, including passerines, use olfaction in many respects of life. During courtship and nest building, male European starlings (Sturnus vulgaris) incorporate aromatic herbs that are rich in volatile compounds (e.g., milfoil, Achillea millefolium) into the nests and they use olfactory cues to identify these plants. Interestingly, European starlings show seasonal differences in their ability to respond to odour cues: odour sensitivity peaks during nest-building in the spring, but is almost non-existent during the non-breeding season.This study used repeated in vivo Manganese-enhanced MRI to quantify for the first time possible seasonal changes in the anatomy and activity of the OB in starling brains. We demonstrated that the OB of the starling exhibits a functional seasonal plasticity of certain plant odour specificity and that the OB is only able to detect milfoil odour during the breeding season. Volumetric analysis showed that this seasonal change in activity is not linked to a change in OB volume. By subsequently experimentally elevating testosterone (T) in half of the males during the non-breeding season we showed that the OB volume was increased compared to controls.By investigating the neural substrate of seasonal olfactory sensitivity changes we show that the starlings' OB loses its ability during the non-breeding season to detect a natural odour of a plant preferred as green nest material by male starlings. We found that testosterone, applied during the non-breeding season, does not restore the discriminatory ability of the OB but has an influence on its size

Segmental Duplications Arise from Pol32-Dependent Repair of Broken Forks through Two Alternative Replication-Based Mechanisms

The propensity of segmental duplications (SDs) to promote genomic instability is of increasing interest since their involvement in numerous human genomic diseases and cancers was revealed. However, the mechanism(s) responsible for their appearance remain mostly speculative. Here, we show that in budding yeast, replication accidents, which are most likely transformed into broken forks, play a causal role in the formation of SDs. The Pol32 subunit of the major replicative polymerase Polδ is required for all SD formation, demonstrating that SDs result from untimely DNA synthesis rather than from unequal crossing-over. Although Pol32 is known to be required for classical (Rad52-dependant) break-induced replication, only half of the SDs can be attributed to this mechanism. The remaining SDs are generated through a Rad52-independent mechanism of template switching between microsatellites or microhomologous sequences. This new mechanism, named microhomology/microsatellite-induced replication (MMIR), differs from all known DNA double-strand break repair pathways, as MMIR-mediated duplications still occur in the combined absence of homologous recombination, microhomology-mediated, and nonhomologous end joining machineries. The interplay between these two replication-based pathways explains important features of higher eukaryotic genomes, such as the strong, but not strict, association between SDs and transposable elements, as well as the frequent formation of oncogenic fusion genes generating protein innovations at SD junctions

Bill color, not badge size, indicates testosterone-related information in house sparrows

The honesty of ornamental signals of quality is often argued to be enforced via costs associated with testosterone. It is still poorly understood, however, how seasonal variation of testosterone within individuals is related to the timing and extent of ornament development. Here, we studied inter- and intra-individual variability of plasma testosterone levels in a population of 150 captive male house sparrows (Passer domesticus) through the course of a full year. We further analyzed the relationship between plasma testosterone levels and two sexually dimorphic ornaments: badge size and bill coloration. Also, because of a known negative relation between molt and circulating testosterone levels, we analyzed the relationship between ornamentation and molt status during the fall. We found that testosterone levels increased towards the breeding season and decreased before the onset of annual molt. However, within individuals, relative testosterone titers demonstrated low repeatability between seasons. Plasma testosterone levels were not correlated with badge size in any season but were correlated strongly with bill coloration during all periods, except the breeding season when variation in bill color was low. Finally, we found that bill coloration strongly correlated with molt status during fall. Our results indicate that bill coloration, not badge size, is the best ornamental indicator of a “running average” of male testosterone in house sparrows and therefore the best potential indicator of qualities and/or behavioral strategies associated with testosterone

Patterns of neonatal hypoxic–ischaemic brain injury

Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic–ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome

Molecular and physiological basis of Saccharomyces cerevisiae tolerance to adverse lignocellulose-based process conditions

Lignocellulose-based biorefineries have been gaining increasing attention to substitute current petroleum-based refineries. Biomass processing requires a pretreatment step to break lignocellulosic biomass recalcitrant structure, which results in the release of a broad range of microbial inhibitors, mainly weak acids, furans, and phenolic compounds. Saccharomyces cerevisiae is the most commonly used organism for ethanol production; however, it can be severely distressed by these lignocellulose-derived inhibitors, in addition to other challenging conditions, such as pentose sugar utilization and the high temperatures required for an efficient simultaneous saccharification and fermentation step. Therefore, a better understanding of the yeast response and adaptation towards the presence of these multiple stresses is of crucial importance to design strategies to improve yeast robustness and bioconversion capacity from lignocellulosic biomass. This review includes an overview of the main inhibitors derived from diverse raw material resultants from different biomass pretreatments, and describes the main mechanisms of yeast response to their presence, as well as to the presence of stresses imposed by xylose utilization and high-temperature conditions, with a special emphasis on the synergistic effect of multiple inhibitors/stressors. Furthermore, successful cases of tolerance improvement of S. cerevisiae are highlighted, in particular those associated with other process-related physiologically relevant conditions. Decoding the overall yeast response mechanisms will pave the way for the integrated development of sustainable yeast cell--based biorefineries.This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the strategic funding of UID/BIO/04469/2013 unit, MIT Portugal Program (Ph.D. grant PD/BD/128247/ 2016 to Joana T. Cunha), Ph.D. grant SFRH/BD/130739/2017 to Carlos E. Costa, COMPETE 2020 (POCI-01-0145-FEDER-006684), BioTecNorte operation (NORTE-01-0145-FEDER-000004), YeasTempTation (ERA-IB-2-6/0001/2014), and MultiBiorefinery project (POCI-01-0145-FEDER-016403). Funding by the Institute for Bioengineering and Biosciences (IBB) from FCT (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (Project N. 007317) was also receiveinfo:eu-repo/semantics/publishedVersio

Asymmetric reproductive isolation between terminal forms of the salamander ring species Ensatina eschscholtzii revealed by fine-scale genetic analysis of a hybrid zone

<p>Abstract</p> <p>Background</p> <p>Ring species, exemplified by salamanders of the <it>Ensatina eschscholtzii </it>complex, represent a special window into the speciation process because they allow the history of species formation to be traced back in time through the geographically differentiated forms connecting the two terminal forms of the ring. Of particular interest is the nature and extent of reproductive isolation between the geographically terminal forms, in this case <it>E. e. eschscholtzii </it>and <it>E. e. klauberi</it>. Previous studies have documented infrequent hybridization at the end of the ring. Here, we report the first fine-scale genetic analysis of a hybrid zone between the terminal forms in southern California using individual-based Bayesian analyses of multilocus genetic data to estimate levels and direction of hybridization and maximum-likelihood analysis of linkage disequilibrium and cline shape to make inferences about migration and selection in the hybrid zone.</p> <p>Results</p> <p>The center of the hybrid zone has a high proportion of hybrids, about half of which were classified as F1s. Clines are narrow with respect to dispersal, and there are significant deviations from Hardy-Weinberg equilibrium as well as nonrandom associations (linkage disequilibria) between alleles characteristic of each parental type. There is cytonuclear discordance, both in terms of introgression and the geographic position of mitochondrial versus nuclear clines. Genetic disequilibrium is concentrated on the <it>eschscholtzii </it>side of the zone. Nearly all hybrids possess <it>klauberi </it>mtDNA, indicating that most hybrids are formed from female <it>klauberi </it>mating with male <it>eschscholtzii </it>or male hybrids (but not vice versa).</p> <p>Conclusions</p> <p>Our results are consistent with a tension zone trapped at an ecotone, with gene combinations characteristic of <it>klauberi </it>showing up on the <it>eschscholtzii </it>side of the zone due to asymmetric hybridization. We suggest that the observed asymmetry is best explained by increased discriminatory power of <it>eschscholtzii </it>females, or asymmetric postzygotic isolation. The relatively high frequency of hybrids, particularly F1s, contrasts with other contacts between the terminal forms, and with other contacts between other divergent <it>Ensatina </it>lineages, highlighting the diverse outcomes of secondary contact within a single species complex.</p

Deficient Induction Response in a Xenopus Nucleocytoplasmic Hybrid

Defects in induction signaling and response underlie the nucleocytoplasmic incompatibility between two evolutionarily distant frog species, while specific treatments partially restore this response in explants and whole embryos

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study

Background: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. Methods: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. Results: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Conclusions: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years