Stability of oligosaccharides derived from lactulose during the processing of milk and apple juice

The scientific evidence on the bioactivity of oligosaccharides from lactulose has encouraged us to study their physicochemical modifications during the processing of milk and apple juice. The carbohydrate fraction with a degree of polymerization ≥3 was stable in milk heated at temperatures up to 100°C for 30 min and in apple juice heated up to 90°C for 15 min. An assessment of the Maillard reaction in heated milk pointed out a higher formation of furosine in milk with oligosaccharides from lactulose as compared to its counterpart without this ingredient, due to a higher presence of galactose. The organoleptic properties of juice with oligosaccharides from lactulose were acceptable and similar to those of apple juice with commercial galactooligosaccharides. The results presented herein demonstrate that oligosaccharides from lactulose can be used as prebiotic ingredients in a wide range of functional foods, including those intended for diabetics and lactose intolerant individuals.This work has been supported by project AGL2011-27884 from Spanish Ministerio de Economía y Competitividad.Peer Reviewe

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Metal bioavailability models: current status, lessons learned, considerations for regulatory use, and the path forward

Since the early 2000s, biotic ligand models and related constructs have been a dominant paradigm for risk assessment of aqueous metals in the environment. We critically review 1) the evidence for the mechanistic approach underlying metal bioavailability models; 2) considerations for the use and refinement of bioavailability‐based toxicity models; 3) considerations for the incorporation of metal bioavailability models into environmental quality standards; and 4) some consensus recommendations for developing or applying metal bioavailability models. We note that models developed to date have been particularly challenged to accurately incorporate pH effects because they are unique with multiple possible mechanisms. As such, we doubt it is ever appropriate to lump algae/plant and animal bioavailability models; however, it is often reasonable to lump bioavailability models for animals, although aquatic insects may be an exception. Other recommendations include that data generated for model development should consider equilibrium conditions in exposure designs, including food items in combined waterborne–dietary matched chronic exposures. Some potentially important toxicity‐modifying factors are currently not represented in bioavailability models and have received insufficient attention in toxicity testing. Temperature is probably of foremost importance; phosphate is likely important in plant and algae models. Acclimation may result in predictions that err on the side of protection. Striking a balance between comprehensive, mechanistically sound models and simplified approaches is a challenge. If empirical bioavailability tools such as multiple‐linear regression models and look‐up tables are employed in criteria, they should always be informed qualitatively and quantitatively by mechanistic models. If bioavailability models are to be used in environmental regulation, ongoing support and availability for use of the models in the public domain are essential

HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10q

Background: Late onset Alzheimer's disease (LOAD) is a neurodegenerative disorder characterised by the deposition of amyloid plaques and neurofibrillary tangles in the brain and is the major cause of dementia. Multiple genetic loci, including 10q, have been implicated in LOAD but to date, with the exception of APOE, the underlying genes have not been identified. HECTD2 maps to 10q and has been implicated in susceptibility to human prion diseases which are also neurodegenerative conditions associated with accumulation of misfolded host proteins. In this study we test whether the HECTD2 susceptibility allele seen in prion disease is also implicated in LOAD.Methods: DNA from 320 individuals with Alzheimer's disease and 601 controls were genotyped for a HECTD2 intronic tagging SNP, rs12249854 (A/T). Groups were further analysed following stratification by APOE genotype.Results: The rs12249854 minor allele (A) frequency was higher (5.8%) in the Alzheimer's disease group as compared to the controls (3.9%), however, this was not statistically significant (P = 0.0668). No significant difference was seen in minor allele frequency in the presence or absence of the APOE epsilon 4 allele.Conclusion: The common haplotypes of HECTD2, tagged by rs12249854, are not associated with susceptibility to LOAD

Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

<p>Abstract</p> <p>Background</p> <p>Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD).</p> <p>Methods</p> <p>Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression.</p> <p>Results</p> <p>There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype.</p> <p>Conclusion</p> <p>This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.</p

Efficacy and Safety of Alirocumab in Individuals with Diabetes Mellitus:Pooled Analyses from Five Placebo-Controlled Phase 3 Studies

Introduction: Diabetes mellitus (DM) carries an elevated risk for cardiovascular disease. Here, we assessed alirocumab efficacy and safety in people with/without DM from five placebo-controlled phase 3 studies. Methods: Data from up to 78 weeks were analyzed in individuals on maximally tolerated background statin. In three studies, alirocumab 75 mg every 2 weeks (Q2W) was increased to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dL; two studies used alirocumab 150 mg Q2W throughout. The primary endpoint was percentage change in LDL-C from baseline to week 24. Results: In the alirocumab 150 mg pool (n = 2416), baseline LDL-C levels were 117.4 mg/dL (DM) and 130.6 mg/dL (without DM), and in the 75/150 mg pool (n = 1043) 112.8 mg/dL (DM) and 133.0 mg/dL (without DM). In the 150 mg Q2W group, week 24 LDL-C reductions from baseline were observed in persons with DM (− 59.9%; placebo, − 1.4%) and without DM (− 60.6%; placebo, + 1.5%); 77.7% (DM) and 76.8% (without DM) of subjects achieved LDL-C < 70 mg/dL. In the alirocumab 75/150 mg group, 26% (DM) and 36% (without DM) of subjects received dose increase. In this group, week 24 LDL-C levels changed from baseline by − 43.8% (DM; placebo, + 0.3%) and − 49.7% (without DM; placebo, + 5.1%); LDL-C < 70 mg/dL was achieved by 68.3% and 65.8% of individuals, respectively. At week 24, alirocumab was also associated with improved levels of other lipids. Adverse event rates were generally comparable in all groups (79.8–82.0%). Conclusions: Regardless of DM status, alirocumab significantly reduced LDL-C levels; safety was generally similar. Funding Sanofi and Regeneron Pharmaceuticals, Inc. Plain Language Summary Plain language summary available for this article. Electronic supplementary material The online version of this article (10.1007/s13300-018-0439-8) contains supplementary material, which is available to authorized users

Seasonal Changes in Physical Qualities of Elite Youth Soccer Players according to Maturity Status: Comparisons with Aged Matched Controls.

Purpose: Longitudinal studies assessing the seasonal development of strength, speed and power qualities are limited in youth soccer players. The purpose of this study was to evaluate the seasonal changes in the physical development of elite youth soccer players across Pre-, Circa- and Post-Peak Height Velocity (PHV), against a similar age and maturity matched control groups. Methods: One-hundred and twelve male elite youth soccer players (Pre-PHV n = 55; Circa-PHV n = 21; Post-PHV n = 36) and 38 controls consisting of non-elite active participants (Pre-PHV n = 18; Circa-PHV n = 10; Post-PHV n = 10) all undertook isometric mid-thigh pull strength, 10–30 m sprints, change of direction speed (CODs) and countermovement jump (CMJ) tests pre- and post-season. Results: The elite Circa-PHV improved greater than the control group for all physical qualities between pre- and post-season. The elite Pre-PHV improved greater in sprints, CODs, CMJ jump height and strength while the elite Post-PHV group improved more in CODs and strength than their respective control groups. Conclusion: Findings suggest that systematic academy soccer training enhances the development of physical qualities in youth soccer players but maturity status may impact upon such adaptations

A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal