Composition and temporal stability of the gut microbiota in older persons

The composition and function of the human gut microbiota has been linked to health and disease. We previously identified correlations between habitual diet, microbiota composition gradients and health gradients in an unstratified cohort of 178 elderly subjects. To refine our understanding of diet–microbiota associations and differential taxon abundance, we adapted an iterative bi-clustering algorithm (iterative binary bclustering of gene sets (iBBiG)) and applied it to microbiota composition data from 732 faecal samples from 371 ELDERMET cohort subjects, including longitudinal samples. We thus identified distinctive microbiota configurations associated with ageing in both community and long-stay residential care elderly subjects. Mixed-taxa populations were identified that had clinically distinct associations. Microbiota temporal instability was observed in both community-dwelling and long-term care subjects, particularly in those with low initial microbiota diversity. However, the stability of the microbiota of subjects had little impact on the directional change of the microbiota as observed for long-stay subjects who display a gradual shift away from their initial microbiota. This was not observed in community-dwelling subjects. This directional change was associated with duration in long-stay. Changes in these bacterial populations represent the loss of the health-associated and youth-associated microbiota components and gain of an elderly associated microbiota. Interestingly, community-associated microbiota configurations were impacted more by the use of antibiotics than the microbiota of individuals in long-term care, as the community-associated microbiota showed more loss but also more recovery following antibiotic treatment. This improved definition of gut microbiota composition patterns in the elderly will better inform the design of dietary or antibiotic interventions targeting the gut microbiota.     

Social Mobility and Mental Disorders at 30 Years of Age in Participants of the 1982 Cohort,Pelotas, Rio Grande Do Sul – RS

This study aimed to evaluate the relationship between mental disorders at 30 years of age and social mobility by formally testing three hypotheses: Risk Accumulation; Critical Period; and Social Mobility. The study was performed using data from the 30-year follow-up of the Pelotas Birth Cohort Study, conducted in 1982, and data from previous follow-ups. The tool used to evaluate mental health was the Self Report Questionnaire (SRQ-20). For the statistical analysis, the chi-square test with the Yates correction was used to estimate the prevalence of mental disorder, and the Poisson regression with robust variance was used to formally test the hypotheses according to the Risk Accumulation, Critical Period and Social Mobility Models. The analyses were stratified by gender. The prevalence of Common Mental Disorders (CMDs) was 24.3% (95% CI 22.9–25.7) when the whole sample was considered. The highest prevalence, 27.1% (95% CI 25.1–29.2), was found in women, and the difference between genders was significant (p < 0.001). CMDs were more frequent in participants who remained “poor” in the three follow-ups. In both men and women, the best fit was obtained with the Risk Accumulation Model, with p = 0.6348 and p = 0.2105, respectively. The results indicate the need to rethink public income maintenance policies. Finally, we suggest further studies to investigate the role of different public policies in decreasing the prevalence of mental disorders and thus contribute proposals of new policies that may contribute to the prevention of these disorders.     

Vimentin-derived proteins : Differences between normal human fibroblasts and transformed human cells

Two-dimensional gel electrophoresis revealed a quantitative difference in a series of polypeptides ranging in MW from 45 000 to 51 000 and of lower isoelectric pH than vimentin, when comparing normal human fibroblasts with a virally transformed subline and with HeLa cells. Re-extraction of purified [³⁵S]vimentin with cold whole cell homogenates and peptide mapping showed that these polypeptides are derivatives of vimentin. They may be natural components of a normal fibroblast's architecture or they may arise from a pool of vimentin that is not structured within intermediate filaments at the time of extraction. Furthermore, we show that vimentin from the two transformed cell types is more resistant to proteolysis by whole cell homogenates than vimentin from normal fibroblasts. Structural alteration of vimentin may play an important role in the expression of transformation.     

Recombination,Pairing, and Synapsis of Homologs during Meiosis

Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.The role of the meiotic program is to generate gametes having half the chromosome complement of the original progenitor cell. This task is accomplished by occurrence of a single round of DNA replication followed by two successive rounds of chromosome segregation. Homologs segregate to opposite poles at meiosis I, then sisters separate to opposite poles in meiosis II, analogously to mitosis (Fig. 1A).Open in a separate windowFigure 1.General features of meiosis. (A) At meiosis I, homologs segregate; at meiosis II, sisters segregate. At metaphase I (left), maternal (red) and paternal (black) chromosomes are held together by a chiasma comprising a reciprocal crossover (CO) plus connections along sister arms, which are released during segregation. (B) Monochiasmate bivalent of Locusta after bromodeoxyuridine (BrdU) incorporation. Differential staining of the sister chromatids confirms that exchange has occurred, for example, between red and purple chromatids in corresponding drawings. (From Jones 1987; reprinted, with permission, from Academic Press © 1987.) (C) Diplotene bivalent of grasshopper with three chiasmata (arrows) and corresponding drawing. (From Jones and Franklin 2006; reprinted, with permission, from Elsevier © 2006.) (D) Top: Meiotic prophase in rye microsporocytes; chromosomes are stained by hematoxylin (pictures by D.Z.). Bottom: corresponding timing of the recombination steps from double-strand breaks (DSBs) to COs; timing of intermediates as in budding yeast (Hunter 2007). SEI, Single-end invasion; dHJ, double Holliday junction; SDSA, synthesis-dependent strand annealing; NCO, noncrossover.During meiosis, a central role of recombination is to increase genetic diversity. However, recombination is also essential for two fundamental features unique to meiotic chromosome mechanics: pairing and segregation of homologous chromosomes (“homologs”). Pairing is mediated by the totality of programmed interhomolog recombinational interactions in association with chromosome structural axes (see below). Segregation is mediated specifically by the carefully chosen subset of those interactions that mature into crossover (CO) products. During segregation of homologs, just as for segregation of sister chromatids, the separating entities must be connected to one another such that regular bipolar alignment on the spindle results in tension on centromere/kinetochore complexes. When all segregating pairs are properly aligned and under tension, anaphase is triggered. Segregation of sisters is ensured by connections between sister centromere/kinetochore regions. Segregation of homologs is ensured by connections along chromosome arms that are provided by the combined effects of an interhomolog CO plus links between sisters (Fig. 1A). These connections can be seen cytologically as chiasmata (Fig. 1B,C). In organisms in which meiosis occurs without recombination, other features have evolved that hold homologs together to ensure regular segregation (Zickler and Kleckner 1998, 1999; reviewed in Stewart and Dawson 2008; Tsai and McKee 2011; Lake and Hawley 2012; Obeso et al. 2014).     

Considerations for the process development of insect‐derived antimicrobial peptide production

Antimicrobial peptides (AMPs) could evolve into new therapeutic lead molecules against multi‐resistant bacteria. As insects are a rich source of AMP, the identification and characterization of insect‐derived AMPs is particularly emphasized. One challenge of bringing these molecules into market, e.g., as a drug, is to develop a cost‐efficient large‐scale production process. Due to the fact that a direct AMP isolation from insects is not economical and that chemical synthesis is recommended for peptide sizes below 40 amino acids, a viable option is heterologous AMP production. Therefore, previous knowledge concerning the expression of larger proteins can be adapted, but due to the AMP nature (e.g., small size, bactericide) additional challenges have to be faced during up and downstream processing. Nonetheless the bottleneck for large‐scale AMP production is the same as for proteins; mainly the downstream process. This review introduces opportunities for insect‐derived AMP production, like the choice of the expression system (based on previously derived data), depending on the AMP nature, as well as new purification strategies like elastin‐like peptide/intein based purification strategies. All of these aspects are discussed with regard to large‐scale processes and costs. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:1–11, 2015     

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Methods

2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials.

Results

Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m², follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I² = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00).

Conclusions

In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.