Triple helix conformation of botryosphaeran, a (1→3;1→6)-β-d-glucan produced by Botryosphaeria rhodina MAMB-05

Botryosphaeran, a (1→3;1→6)-β-d-glucan produced by Botryosphaeria rhodina MAMB-05, was found to be present in a triple helix conformation from helix–coil transition studies using Congo Red. The triple helix conformation was disrupted at increasing alkali concentrations. Conformational changes were also observed using phenanthrene as a fluorescent probe, and the fluorescence intensity decreased 80% in the presence of dimethyl sulfoxide. The results confirmed the triple helix conformation of botryosphaeran, an important property manifesting biological response modifying activity.     

Importance of Weight Loss Maintenance and Risk Prediction in the Prevention of Type 2 Diabetes: Analysis of European Diabetes Prevention Study RCT

Background

Prevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial cohorts: to analyse T2D incidence, sustained weight loss and utility of risk predictors.

Methods

We analysed data on 749 adults with impaired glucose tolerance (278 men and 471 women, mean age 56 years, mean BMI 31 kgm⁻²) recruited between 1993 and 2003, and randomised to intensive lifestyle intervention (I) or lifestyle advice control (C). The intervention aimed to increase physical activity, modify diet, and promote weight loss≥5%. Using Cox-regression survival analysis, we assessed T2D incidence and the impact on T2D incidence of sustained weight loss, and of baseline cut-point values of FINDRISC score, fasting plasma glucose (FPG), and HbA_1c.

Results

Mean follow-up duration was 3.1 years. T2D was diagnosed in 139 participants (I = 45/379, C = 94/370). Cumulative T2D incidence was 57% lower in the intervention compared with the control group (HR 0.42 (95% CI 0.29 to 0.60) P<0.001). Participants with ≥5% weight loss at one year had 65% lower T2D incidence (HR 0.35 (95% CI 0.22 to 0.56) P<0.001); maintaining ≥5% weight loss for two and three years further reduced T2D incidence. Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study (EDIPS) participants with similar hazard-ratios for intervention effect.

Conclusions

Pooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention. Analysis showed the preventive effect of ≥5% weight loss, especially if maintained long term, which has utility for intervention monitoring. Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit, to efficiently target interventions and suggests evidence is needed to define clinical policy.

Trial registrations

The Finnish Diabetes Prevention study, Helsinki, Finland: ClinicalTrials.gov; {"type":"clinical-trial","attrs":{"text":"NCT00518167","term_id":"NCT00518167"}}NCT00518167 The SLIM diabetes prevention study, Maastricht, The Netherlands: Clinical Trials.gov; {"type":"clinical-trial","attrs":{"text":"NCT00381186","term_id":"NCT00381186"}}NCT00381186 The EDIPS-Newcastle diabetes prevention study, Newcastle upon Tyne, UK: International Standard Randomised Controlled Trial Number; ISRCTN15670600.     

Exopolysaccharides produced by Lactococcus lactis: from genetic engineering to improved rheological properties?

Over the last years, important advances have been made in the study of the production of exopolysaccharides (EPS) by several lactic acid bacteria, including Lactococcus lactis. From different EPS-producing lactococcal strains the specific eps gene clusters have been characterised. They contain eps genes, which are involved in EPS repeating unit synthesis, export, polymerisation, and chain length determination. The function of the glycosyltransferase genes has been established and the availability of these genes opened the way to EPS engineering. In addition to the eps genes, biosynthesis of EPS requires a number of housekeeping genes that are involved in the metabolic pathways leading to the EPS-building blocks, the nucleotide sugars. The identification and characterisation of several of these housekeeping genes (galE, galU, rfbABCD) allows the design of metabolic engineering strategies that should lead to increased EPS production levels by L. lactis. Finally, model developme nt has been initiated in order to predict the physicochemical consequences of the addition of a EPS to a product.     

The role of parametric linkage methods in complex trait analyses using microsatellites

Many investigators of complexly inherited familial traits bypass classical segregation analysis to perform model-free genome-wide linkage scans. Because model-based or parametric linkage analysis may be the most powerful means to localize genes when a model can be approximated, model-free statistics may result in a loss of power to detect linkage. We performed limited segregation analyses on the electrophysiological measurements that have been collected for the Collaborative Study on the Genetics of Alcoholism. The resulting models are used in whole-genome scans. Four genomic regions provided a model-based LOD > 2 and only 3 of these were detected (p < 0.05) by a model-free approach. We conclude that parametric methods, using even over-simplified models of complex phenotypes, may complement nonparametric methods and decrease false positives.     

Selected topics in probiotics and prebiotics: meeting report for the 2004 international scientific association for probiotics and prebiotics

On August 29-31, 2004, 84 academic and industry scientists from 16 countries gathered in Copper Mountain, Colorado USA to discuss certain issues at the forefront of the science of probiotics and prebiotics. The format for this invitation only meeting included six featured lectures: engineering human vaginal lactobacilli to express HIV-inhibitory molecules (Peter Lee, Stanford University), programming the gut for health (Thaddeus Stappenbeck, Washington University School of Medicine), immune modulation by intestinal helminthes (Joel Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of autoimmune disorders (G. A. Rook, University College London), prebiotics and bone health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all participants were included in one of eight discussion groups on the topics of engineered probiotics, host-commensal bacteria communication, 'omics' technologies, hygiene and immune regulation, biomarkers for healthy people, prebiotic and probiotic applications to companion animals, development of a probiotic dossier, and physiological relevance of prebiotic activity. Brief conclusions from these discussion groups are summarized in this paper.     

No Effects of Successful Bidirectional SMR Feedback Training on Objective and Subjective Sleep in Healthy Subjects

There is a growing interest in the application of psychophysiological signals in more applied settings. Unidirectional sensory motor rhythm-training (SMR) has demonstrated consistent effects on sleep. In this study the main aim was to analyze to what extent participants could gain voluntary control over sleep-related parameters and secondarily to assess possible influences of this training on sleep metrics. Bidirectional training of SMR as well as heart rate variability (HRV) was used to assess the feasibility of training these parameters as possible brain computer interfaces (BCI) signals, and assess effects normally associated with unidirectional SMR training such as the influence on objective and subjective sleep parameters. Participants (n?=?26) received between 11 and 21 training sessions during 7 weeks in which they received feedback on their personalized threshold for either SMR or HRV activity, for both up- and down regulation. During a pre- and post-test a sleep log was kept and participants used a wrist actigraph. Participants were asked to take an afternoon nap on the first day at the testing facility. During napping, sleep spindles were assessed as well as self-reported sleep measures of the nap. Although the training demonstrated successful learning to increase and decrease SMR and HRV activity, no effects were found of bidirectional training on sleep spindles, actigraphy, sleep diaries, and self-reported sleep quality. As such it is concluded that bidirectional SMR and HRV training can be safely used as a BCI and participants were able to improve their control over physiological signals with bidirectional training, whereas the application of bidirectional SMR and HRV training did not lead to significant changes of sleep quality in this healthy population.     

Aberrant DNA Methylation: Implications in Racial Health Disparity

BackgroundIncidence and mortality rates of colorectal carcinoma (CRC) are higher in African Americans (AAs) than in Caucasian Americans (CAs). Deficient micronutrient intake due to dietary restrictions in racial/ethnic populations can alter genetic and molecular profiles leading to dysregulated methylation patterns and the inheritance of somatic to germline mutations.ResultsDNA from the tumor of AA CRC patients, compared to adjacent normal tissues, contained 1,588 hypermethylated and 100 hypomethylated differentially methylated regions (DMRs). Whereas, 109 hypermethylated and 4 hypomethylated DMRs were observed in DNA from the tumor of CA CRC patients; representing a 14.6-fold and 25-fold change, respectively. Specifically; CHL1, 4 anti-inflammatory genes (i.e., NELL1, GDF1, ARHGEF4, and ITGA4), and 7 miRNAs (of which miR-9-3p and miR-124-3p have been implicated in CRC) were hypermethylated in DNA samples from AA patients with CRC. From the same sample set, RNAseq analysis revealed 108 downregulated genes (including 14 ribosomal proteins) and 34 upregulated genes (including POLR2B and CYP1B1 [targets of miR-124-3p]) in AA patients with CRC versus CA patients.ConclusionDNA methylation profile and/or products of its downstream targets could serve as biomarker(s) addressing racial health disparity.     

Genetic differences among populations in sexual dimorphism: evidence for selection on males in a dioecious plant

Genetic variation among populations in the degree of sexual dimorphism may be a consequence of selection on one or both sexes. We analysed genetic parameters from crosses involving three populations of the dioecious plant Silene latifolia, which exhibits sexual dimorphism in flower size, to determine whether population differentiation was a result of selection on one or both sexes. We took the novel approach of comparing the ratio of population differentiation of a quantitative trait (Q(ST) ) to that of neutral genetic markers (F(ST) ) for males vs. females. We attributed 72.6% of calyx width variation in males to differences among populations vs. only 6.9% in females. The Q(ST) /F(ST) ratio was 4.2 for males vs. 0.4 for females, suggesting that selection on males is responsible for differentiation among populations in calyx width and its degree of sexual dimorphism. This selection may be indirect via genetic correlations with other morphological and physiological traits.     

Core and intact polar glycerol dibiphytanyl glycerol tetraether lipids of ammonia-oxidizing archaea enriched from marine and estuarine sediments

Glycerol dibiphytanyl glycerol tetraether (GDGT)-based intact membrane lipids are increasingly being used as complements to conventional molecular methods in ecological studies of ammonia-oxidizing archaea (AOA) in the marine environment. However, the few studies that have been done on the detailed lipid structures synthesized by AOA in (enrichment) culture are based on species enriched from nonmarine environments, i.e., a hot spring, an aquarium filter, and a sponge. Here we have analyzed core and intact polar lipid (IPL)-GDGTs synthesized by three newly available AOA enriched directly from marine sediments taken from the San Francisco Bay estuary ("Candidatus Nitrosoarchaeum limnia"), and coastal marine sediments from Svalbard, Norway, and South Korea. Like previously screened AOA, the sedimentary AOA all synthesize crenarchaeol (a GDGT containing a cyclohexane moiety and four cyclopentane moieties) as a major core GDGT, thereby supporting the hypothesis that crenarchaeol is a biomarker lipid for AOA. The IPL headgroups synthesized by sedimentary AOA comprised mainly monohexose, dihexose, phosphohexose, and hexose-phosphohexose moieties. The hexose-phosphohexose headgroup bound to crenarchaeol was common to all enrichments and, in fact, the only IPL common to every AOA enrichment analyzed to date. This apparent specificity, in combination with its inferred lability, suggests that it may be the most suitable biomarker lipid to trace living AOA. GDGTs bound to headgroups with a mass of 180 Da of unknown structure appear to be specific to the marine group I.1a AOA: they were synthesized by all three sedimentary AOA and "Candidatus Nitrosopumilus maritimus"; however, they were absent in the group I.1b AOA "Candidatus Nitrososphaera gargensis."