3-D struktura serumske paraoksonaze 1 objašnjava njezinu aktivnost, stabilnost, topljivost i kristalizaciju

Serum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases. PON1 and PON3 reside on high-density lipoprotein (HDL) (the “good cholesterol”), and are involved in the alleviation of atherosclerosis. Members of the PON family have been identified not only in mammals and other vertebrates, but also in invertebrates. We earlier described the first crystal structure of a PON family member, a directly-evolved variant of PON1, at 2.2 Å resolution. PON1 is a 6-bladed beta-propeller with a unique active-site lid which is also involved in binding to HDL. The 3-D structure, taken together with directed evolution studies, permitted analysis of mutations which enhanced the stability, solubility and crystallizability of this PON1 variant. The structure permits a detailed description of PON1’s active site and suggests possible mechanisms for its catalytic activity on certain substrates.Serumske paraoksonaze (PONs) imaju široki raspon fiziološki važnih hidrolitičkih aktivnosti uključujući metabolizam lijekova i detoksikaciju nervnih plinova. PON1 i PON3 smještene su na lipoproteinima visoke gustoće (engl. high-density lipoprotein; HDL - “dobri kolesterol”) i uključene su u ublažavanje ateroskleroze. Članovi skupine PON identificirani su ne samo u sisavaca i drugih kralježnjaka već i kod beskralješnjaka. Prije smo opisali prvu kristalnu strukturu člana PON skupine, direktno razrađenu varijantu PON1 pri rezoluciji 2,2 Å. PON1 je beta-propeler sa šest lopatica s jedinstvenim poklopcem aktivnog mjesta, koji je tako|er uključen u vezanje na HDL. 3-D struktura, gledana zajedno s direktnim razvojnim istraživanjima, omogućila je analizu mutacija koje povećavaju stabilnost, topljivost i kristalizaciju te PON1 varijante. Struktura dopušta detaljan opis aktivnog mjesta PON1 i sugerira moguće mehanizme za njezinu katalitičku aktivnost prema odre|enim supstratima

Changing perceptions of hunger on a high nutrient density diet

<p>Abstract</p> <p>Background</p> <p>People overeat because their hunger directs them to consume more calories than they require. The purpose of this study was to analyze the changes in experience and perception of hunger before and after participants shifted from their previous usual diet to a high nutrient density diet.</p> <p>Methods</p> <p>This was a descriptive study conducted with 768 participants primarily living in the United States who had changed their dietary habits from a low micronutrient to a high micronutrient diet. Participants completed a survey rating various dimensions of hunger (physical symptoms, emotional symptoms, and location) when on their previous usual diet versus the high micronutrient density diet. Statistical analysis was conducted using non-parametric tests.</p> <p>Results</p> <p>Highly significant differences were found between the two diets in relation to all physical and emotional symptoms as well as the location of hunger. Hunger was not an unpleasant experience while on the high nutrient density diet, was well tolerated and occurred with less frequency even when meals were skipped. Nearly 80% of respondents reported that their experience of hunger had changed since starting the high nutrient density diet, with 51% reporting a dramatic or complete change in their experience of hunger.</p> <p>Conclusions</p> <p>A high micronutrient density diet mitigates the unpleasant aspects of the experience of hunger even though it is lower in calories. Hunger is one of the major impediments to successful weight loss. Our findings suggest that it is not simply the caloric content, but more importantly, the micronutrient density of a diet that influences the experience of hunger. It appears that a high nutrient density diet, after an initial phase of adjustment during which a person experiences "toxic hunger" due to withdrawal from pro-inflammatory foods, can result in a sustainable eating pattern that leads to weight loss and improved health. A high nutrient density diet provides benefits for long-term health as well as weight loss. Because our findings have important implications in the global effort to control rates of obesity and related chronic diseases, further studies are needed to confirm these preliminary results.</p

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Efficacy of a Plant-Based Anti-Inflammatory Diet as Monotherapy in Psoriasis

Psoriasis is an immune-mediated disease associated with many comorbidities, including obesity, metabolic syndrome and cardiovascular disease. Many patients seek alternatives to standard treatments. In this case report, we present a non-obese patient who was able to completely clear her psoriatic plaques by following a plant-based, anti-inflammatory diet, focusing on the consumption of nutrient-dense foods. The efficacy of this anti-inflammatory diet may lie in the overall reduction of the systemic inflammatory state associated with psoriasis. Possible mechanisms of action are explored

A Worksite Nutrition Intervention is Effective at Improving Employee Well-Being: A Pilot Study

Background. Worksite dietary interventions show substantial potential for improving employee health and well-being. The aim of this pilot study was to determine the effect of a worksite nutrition intervention on improving well-being. Methods. Thirty-five university employees participated in a 6-week nutrition intervention. The dietary protocol emphasized the daily consumption of greens, beans/legumes, a variety of other vegetables, fruits, nuts, seeds, and whole grains, referred to as a micronutrient-dense, plant-rich diet. Participants were encouraged to minimize the consumption of refined foods and animal products. Results. Significant improvements in sleep quality, quality of life, and depressive symptoms were found. Conclusions. Findings reveal that a worksite nutrition intervention is effective at improving sleep quality, quality of life, and depressive symptoms with a projected improvement in work productivity and attendance

The Pittsburgh Lung Screening Study (PLuSS): Outcomes within 3 Years of a First Computed Tomography Scan

Rationale: The role of computed tomography (CT) screening for lung cancer is controversial, currently under study, and not yet fully elucidated