Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children

Serum Carotenoids and Pediatric Metabolic Index Predict Insulin Sensitivity in Mexican American Children

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10–18 and h2 = 0.58, P = 1 × 10–7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (− 0.22), waist circumference (− 0.25), triglycerides (− 0.18), fat mass (− 0.23), fasting glucose (− 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (− 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children

A Collaborative Requirement Mining Framework to Support OEMs

With the fastidiously ever-increasing complexity of systems, the relentless, massive customisation of products and the mushrooming accumulation of legal documents (standards, policies and laws), we can observe a significant increase in requirements. We consider the tremendous volume of requirements as big data with which companies struggle to make strategic decisions early on. This paper proposes a collaborative requirement mining framework to enable the decision-makers of an Original Equipment Manufacturer (OEM) to gain insight and discover opportunities in a massive set of requirements so as to make early effective strategic decisions. The framework supports OEMs willing to uncover a subset of key requirements by distilling large unstructured and semistructured specifications.Keonys, Toulouse, Franc

Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 Å resolution and two structures of HP HA at 2.95 and 3.10 Å resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species

Establishing a large-scale Greenhouse Gas Removal sector in the United Kingdom by 2030: First mover dilemmas

In June 2019 the UK legislated a 2050 net-zero emissions target. This will require the realisation of a technical Greenhouse Gas Removal (GGR) sector potentially generating over 60 MtCO2 pa of negative emissions by 2050. In October 2021, the UK pledged that at least 5 MtCO2 of engineered negative emissions be deployed by 2030. At present less than 0.5 ktCO2 pa of engineered negative emissions are deployed. The 10,000-fold scale-up to 2030 will require the co-ordinated engagement of first movers to establish and realise at least one GGR value chain. The 120,000-fold scale up to 2050 will require the integration of multiple GGR value chains with existing infrastructure systems and substantive societal engagement to enhance positive social outcomes. This scaling is fundamental to the UK, and arguably international efforts, to address the worst impacts of climate change. A series of exploratory exercises have been undertaken to identify the financial and non-financial barriers to the establishment of a UK multi-MtCO2 pa scale GGR sector from a first mover perspective. This is the first synthesis of first mover drivers in the UK GGR sector. The key findings include: (1) The GGR sector represents a multi-billion pound opportunity in 2050; and (2) inspite of this opportunity - as the incentive, policy, regulatory and governance ecosystem presently stands - first movers face too much risk, uncertainty and a multiplicity of dilemmas to commit substantive investments in establishing the UK GGR multi-MtCO2 pa sector

RE-SWOT: From User Feedback to Requirements via Competitor Analysis

App store reviews are a rich source for analysts to elicit requirements from user feedback, for they describe bugs to be fixed, requested features, and possible improvements. Product development teams need new techniques that help them make real-time decisions based on user feedback. [Question/Problem] Researchers have proposed natural language processing (NLP) techniques for extracting and organizing requirements-relevant knowledge from the reviews for one specific app. However, no attention has been paid to studying whether and how requirements can be identified from competing products. [Principal ideas/results] We propose RE-SWOT, a tool-supported method for eliciting requirements from app store reviews through competitor analysis. RE-SWOT combines NLP algorithms with information visualization techniques. We evaluate the usefulness of RE-SWOT with expert product managers from three mobile app companies. [Contribution] Our preliminary results show that competitor analysis is a promising path for research that has direct impact on the requirements engineering practice in modern app development companies

RE-SWOT: From User Feedback to Requirements via Competitor Analysis

App store reviews are a rich source for analysts to elicit requirements from user feedback, for they describe bugs to be fixed, requested features, and possible improvements. Product development teams need new techniques that help them make real-time decisions based on user feedback. [Question/Problem] Researchers have proposed natural language processing (NLP) techniques for extracting and organizing requirements-relevant knowledge from the reviews for one specific app. However, no attention has been paid to studying whether and how requirements can be identified from competing products. [Principal ideas/results] We propose RE-SWOT, a tool-supported method for eliciting requirements from app store reviews through competitor analysis. RE-SWOT combines NLP algorithms with information visualization techniques. We evaluate the usefulness of RE-SWOT with expert product managers from three mobile app companies. [Contribution] Our preliminary results show that competitor analysis is a promising path for research that has direct impact on the requirements engineering practice in modern app development companies

Characterization of Microbial Dysbiosis and Metabolomic Changes in Dogs with Acute Diarrhea

<div><p>Limited information is available regarding the metabolic consequences of intestinal dysbiosis in dogs with acute onset of diarrhea. The aim of this study was to evaluate the fecal microbiome, fecal concentrations of short-chain fatty acids (SCFAs), as well as serum and urine metabolites in healthy dogs (n=13) and dogs with acute diarrhea (n=13). The fecal microbiome, SCFAs, and serum/urine metabolite profiles were characterized by 454-pyrosequencing of the 16S rRNA genes, GC/MS, and untargeted and targeted metabolomics approach using UPLC/MS and HPLC/MS, respectively. Significantly lower bacterial diversity was observed in dogs with acute diarrhea in regards to species richness, chao1, and Shannon index (p=0.0218, 0.0176, and 0.0033; respectively). Dogs with acute diarrhea had significantly different microbial communities compared to healthy dogs (unweighted Unifrac distances, ANOSIM p=0.0040). While Bacteroidetes, <i>Faecalibacterium</i>, and an unclassified genus within Ruminococcaceae were underrepresented, the genus <i>Clostridium</i> was overrepresented in dogs with acute diarrhea. Concentrations of fecal propionic acid were significantly decreased in acute diarrhea (p=0.0033), and were correlated to a decrease in <i>Faecalibacterium</i> (ρ=0.6725, p=0.0332). The predicted functional gene content of the microbiome (PICRUSt) revealed overrepresentations of genes for transposase enzymes as well as methyl accepting chemotaxis proteins in acute diarrhea. Serum concentrations of kynurenic acid and urine concentrations of 2-methyl-1H-indole and 5-Methoxy-1H-indole-3-carbaldehyde were significantly decreased in acute diarrhea (p=0.0048, 0.0185, and 0.0330, respectively). These results demonstrate that the fecal dysbiosis present in acute diarrhea is associated with altered systemic metabolic states.</p></div