New Apolipoprotein A-V: comparative genomicsmeetsmetabolism

Summary The availability of the human genome sequence and the recently completed draft sequences of two major mammalian model species, the mouse (Mus musculus) and the rat (Rattus norvegicus), allow researchers to apply novel approaches for gene identification and characterization, using methods of comparative and functional genomics. Recently, a new gene coding for apolipoprotein A-V was identified in the vicinity of APOA-I/C-III/A-IV cluster on human chromosome 11q23 by comparative sequencing method. In a relatively short time, compelling evidence accumulated for the substantial role of APOA-V in lipid metabolism. Studies in knock-out and transgenic mice revealed that its expression pattern correlates negatively with triglyceride levels. This observation was verified in human population studies in variety of ethnic and age groups. Several single nucleotide polymorphisms were described and particular SNP alleles and haplotypes in the APO A-V gene region were shown to be associated with dyslipidemia. The discovery and characterization of the APO A-V demonstrates current possibilities of the integrative approaches in biology, boosted by the available bioinformatic tools

PPARs: Molecular Targets in the Pharmacogenomics Era

Abstract: The recent global increase in prevalence of diseases like obesity, type 2 diabetes and hypertension in westernized societies is unfortunately not paralleled by our full understanding of the causative mechanisms. It is now firmly established that the interacting genetic and environmental (diet, smoking) components together determine the development and severity of the particular condition, which makes detailed dissection of such complex traits even more complicated. In effect, there is an unmet urgent need for molecular targets so we can directly modulate the causative factors and devise effective preventive and therapeutic algorithms. Among the most promising molecular targets for treatment of metabolic syndrome-related conditions identified so far, the group of three lipidsensors, the peroxisome proliferator-activated receptors (PPARs) clearly stands out. The review focuses on pharmacogenetic aspects of recent developments in PPAR biology. Key words: PPAR -Systems biology -Pharmacogenetics -Thiazolidinediones -cd36 This work was supported by following grants: GAAV ČR B5105401 from the Grant Agency of the Academy of Sciences of the Czech Introduction Global epidemics of diseases like obesity, type 2 diabetes mellitus, hypertension or dyslipidemia represent a major health issue of today's world. These entities, often clustering under what becomes known as metabolic syndrome Among the most promising molecular targets for treatment of metabolic syndrome-related conditions, the group of three peroxisome proliferator-activated receptors (PPARs) clearly stands out. The first PPAR being identified in 1990, thousands of papers later we are uncovering, step-by-step, their integrative and orchestrating roles in lipid and carbohydrate metabolism, atherogenesis or cancer. PPARs are high on the lists of potential candidate genes for obesity As there are several excellent reviews available discussing the role of PPARs in obesit

Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Levels of pentosidine (representative of advanced glycation end-products) in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls. These levels have been reported to correlate with clinical indices of rheumatoid arthritis activity and with laboratory markers of inflammation. The purpose of this study was to find out if these findings pertain to other advanced glycation end-products.</p> <p>Methods</p> <p>We have developed two immunoassays based on new monoclonal antibodies to advanced glycation end-products. Antibody 103-E3 reacts with an unidentified antigen, formed in the reaction of proteins with ribose, while antibody 8-C1 responds to N^ε-(carboxyethyl)lysine. We have used these monoclonal antibodies to measure levels of advanced glycation end-products in sera of patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and healthy controls. We calculated the correlations between advanced glycation end-product levels in rheumatoid arthritis sera and the Disease Activity Score 28 (DAS28), age, disease duration, CRP, anti-CCP, rheumatoid factor and treatment with corticosteroids, respectively.</p> <p>Results</p> <p>Levels of both glycation products were significantly higher in sera of patients with rheumatoid arthritis when compared with sera of patients with systemic lupus erythematosus, osteoarthritis, or the healthy controls. Neither the level of N^ε-(carboxyethyl)lysine nor the level of the 103-E3 antigen in rheumatoid arthritis sera correlated with the DAS28-scored rheumatoid arthritis activity. The levels of both antigens in rheumatoid arthritis sera did not correlate with age, gender, corticosteroid treatment, or levels of CRP, anti-CCP antibodies, and rheumatoid factor in sera.</p> <p>Conclusions</p> <p>We report highly specific increases in the levels of two advanced glycation end-products in sera of patients with rheumatoid arthritis. This increase could be explained neither by rheumatoid arthritis activity nor by inflammation. We propose a working hypothesis that presumes the existence of a link between advanced glycation end-product formation and induction of autoimmunity.</p

Ten new insights in climate science 2022

Non-technical summary We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C. Technical summary We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C. Social media summary Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields

Częstość występowania otyłości wśród mieszkańców Kraju Południowoczeskiego

Lifestyle diseases constitute a group of diseases whose prevalence has constantly risen since the 1960s. They are closely associated with lifestyle. The modifiable risk factors that include, for example, eating behaviour, leisure-time activity, physical activity and exposure to stress contribute significantly to that trend. The fact that most of the factors are modifiable underlines the importance of primary and secondary prevention. Overweight, obesity and cardiovascular diseases are diseases that should be paid particular attention. The reason consists in the significant increase in their prevalence and the serious consequences connected with those illnesses. According to the data from the European Health Interview Survey (EHIS), 54% of the adult population of the Czech Republic are overweight. From that number, 17% of the population suffer from obesity [3]. Similar results are presented also by the conclusions of the Health Interview Survey published in January 2011. There is a significant shift in the trend to lower ages [5]. The severity of the consequences of an increasing prevalence of cardiovascular diseases is demonstrated by the fact that every year in the Czech Republic about 600 individuals out of 100 000 inhabitants die as a result of them. That constitutes more than 50% of all deaths [1]. This article draws attention to the results of an investigation carried out within the activities of the Prevention Centre in 2011-2012 that examined a total of 346 people over 18 years of age, 267 of them females and 79 males. The values of blood sugar and cholesterol from peripheral blood, blood pressure, height and weight were observed. Also the BMI value and total amount of body fat were measured using the Omron Body Fat Monitor. This device allows the measuring of the total amount of body fat based on bioelectrical impedance.Choroby cywilizacyjne stanowią grupę chorób, których częstość występowania od lat 60-tych XX wieku stale wzrasta. Są ściśle powiązane ze stylem życia. Modyfikowalne czynniki ryzyka, które przykładowo obejmują nawyki żywieniowe, sposób spędzania czasu wolnego, aktywność fizyczną i narażenie na stres, w sposób istotny wpływają na ten trend. To, że większość tych czynników jest modyfikowalna, podkreśla znaczenie profilaktyki pierwotnej i wtórnej. Należy zwrócić szczególną uwagę na nadwagę, otyłość i choroby sercowo-naczyniowe. Wynika to z istotnego wzrostu częstości występowania oraz poważnych skutków tych schorzeń. Według danych pochodzących z europejskiego ankietowego badania zdrowia ludności (EHIS), 54% dorosłych mieszkańców Czech ma nadwagę. Co więcej, 17% osób należących do tej grupy cierpi na otyłość [3]. Podobne wyniki przedstawiają także wnioski z ankietowego badania zdrowia ludności opublikowane w styczniu 2011 roku. Trend ten uległ istotnemu przesunięciu w kierunku młodszych grup wiekowych [5]. Powagę skutków wzrastającej częstości występowania chorób sercowo-naczyniowych potwierdza fakt, że co roku w Czechach około 600 na 100.000 mieszkańców umiera w ich rezultacie. Liczba ta stanowi ponad 50% całkowitej liczby zgonów [1]. Niniejszy artykuł zwraca uwagę na wyniki badania przeprowadzonego w ramach działalności Ośrodka Profilaktyki w latach 2011-2012, które objęło ogółem 346 osób powyżej 18. roku życia, z których 267 było płci żeńskiej, a 79 – męskiej. Obserwowano wartości stężenia cukru i cholesterolu we krwi obwodowej, ciśnienia krwi, wzrost i wagę. Mierzono także wartość współczynnika BMI oraz całkowitą ilość tkanki tłuszczowej w organizmie przy użyciu urządzenia do pomiaru tkanki tłuszczowej firmy Omron. Aparat ten pozwala na określenie całkowitej ilości tkanki tłuszczowej w organizmie w oparciu o metodę pomiaru impedancji bioelektrycznej

Ten new insights in climate science 2022

Non-technical summary We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate-health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C. Technical summary We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate-health horizon - some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C. Social media summary Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields