Dietary resveratrol prevents alzheimer's markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer's disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.

Decades of population genetic research reveal the need for harmonization of molecular markers: the grey wolf Canis lupus as a case study

Following protection measures implemented since the 1970s, large carnivores are currently increasing in number and returning to areas from which they were absent for decades or even centuries. Monitoring programmes for these species rely extensively on non-invasive sampling and genotyping. However, attempts to connect results of such studies at larger spatial or temporal scales often suffer from the incompatibility of genetic markers implemented by researchers in different laboratories. This is particularly critical for long-distance dispersers, revealing the need for harmonized monitoring schemes that would enable the understanding of gene flow and dispersal dynamics. Based on a review of genetic studies on grey wolves Canis lupus from Europe, we provide an overview of the genetic markers currently in use, and identify opportunities and hurdles for studies based on continent-scale datasets. Our results highlight an urgent need for harmonization of methods to enable transnational research based on data that have already been collected, and to allow these data to be linked to material collected in the future. We suggest timely standardization of newly developed genotyping approaches, and propose that action is directed towards the establishment of shared single nucleotide polymorphism panels, next-generation sequencing of microsatellites, a common reference sample collection and an online database for data exchange. Enhanced cooperation among genetic researchers dealing with large carnivores in consortia would facilitate streamlining of methods, their faster and wider adoption, and production of results at the large spatial scales that ultimately matter for the conservation of these charismatic species.

Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G.C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G.C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response toa nutritional interventionwithMD.An intervention study ina high cardiovascular riskMediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplementedwith virgin olive oil ornuts.Measureswereobtained at baseline and after a 3-mointervention period.At baseline, the COX-2 -765G.C polymorphismwas associated with lower serum IL-6 (5.85 6 4.82 in GG vs. 4.74 6 4.14 ng/L in C-allele carriers; P ¼ 0.002) and ICAM-1 (265.8 6 114.8 in GG vs. 243.0 6 107.1 mg/L in C-carriers; P ¼ 0.018) concentrations. These differences remained significant aftermultivariate adjustment. The IL-6 -174G.C polymorphism was associatedwith higher (CC vs. G-carriers) serumICAM-1concentrations in bothmenandwomenandwithhigherserumIL-6 concentrations inmen.Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G.C and IL-6 -174G.C polymorphismswere associatedwith inflammation, consuming aMD(either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.

Role of immune and angiogenic markers in the pathology of endometriosis

Background: Endometriosis is an estrogen-dependent, pro-inflammatory, pro-angiogenic condition that affects 5 to 10% of women of reproductive age. Its defining feature is the presence of endometrium-like tissue in sites outside the uterine cavity, primarily on the pelvic peritoneum and ovaries. The main clinical features are chronic pain, pain during intercourse and infertility. In patients with endometriosis, inflammatory and immune responses, angiogenesis and apoptosis are altered in favour of the survival and replenishment of endometriotic tissue. These basic pathological processes depend on the excessive formation of estrogen and prostaglandins. Recently, new cellular and molecular mechanisms for the resolution of inflammation have been discovered, revealing key roles for lipid mediators such as lipoxins, resolvins and protectins. It is possible that disequilibrium in the expression of these molecules exists in endometriosis. Objective: To compare the expression of two proteins involved in the synthe sis and in the function of lipid mediators; the Arachidonate 15-lipoxygenase (ALOXI5), implicated in the synthesis of lipoxins A4 and B4 and the Formyl peptide receptor 1 (FPRLI), the specific receptor for Lipoxin A4 and B4, between women who suffer from endometriosis and a control group. We wish to demonstrate the cellular localisation of these two molecules and to investigate if their expression is alteted in this pathology. Methods and Materials Using immunohistochemistry we will compare ALOXI5 and FPRLI staining, in endometrium, normal peritoneum and endometriotic lesions. The samples are being collected in the department of Gynaecology and Obstetrics at the Centre Hospitalier Universitaire Lausanne (CHUV). Women attending the department for laparoscopic investigation of pain/infertility, suspected endometriosis or for a hysterectomy, are invited to participate. Approval of the ethics committee (Commission d'Ethique de la recherché clinique) was obtained in March 2009. Clinical samples will only be obtained from subjects having consented. Expected results and interpretation: No published studies investigating the expression of these two molecules in endometriotic lesions exist. A better understanding of the mechanisms underlying this disease will result in the development of new medical therapies and new diagnostic tests, with the aim of ameliorating the quality of life of endometriosis patients.

Angiotensin receptor blockers are not associated with reduced inflammatory markers in the general population.

OBJECTIVE: Angiotensin receptor blockers (ARBs) have been suggested to reduce inflammation in randomized controlled trials. We assessed the association between ARBs and inflammatory markers in a general population setting. METHODS: This is a population-based prospective study conducted in Lausanne, Switzerland. Baseline data from 933 participants on antihypertensive drugs (424 on ARBs) was collected in 2003-2006. Follow-up data from 1120 participants (572 on ARBs) was collected in 2009-2012. C-reactive protein (CRP), interleukins 1β and 6 and tumor necrosis factor alpha (TNF-α) were assessed and categorized in quartiles. RESULTS: At baseline, no differences were found between participants taking or not taking ARBs for all inflammatory markers studied, and this association persisted after multivariate adjustment: odds ratios (ORs) and (95% confidence interval) for being in the highest quartile of interleukin-1β, interleukin-6, TNF-α and CRP for participants on ARB compared to participants not on ARB were 1.23 (0.89-1.70), 1.26 (0.93-1.70), 1.14 (0.85-1.53) and 1.27 (0.96-1.69) respectively (P > 0.05). These findings were further replicated in the follow-up study: OR and (95% CI) of 1.10 (0.78-1.55), 0.87 (0.64-1.19), 0.83 (0.61-1.14) and 0.91 (0.68-1.22) for interleukin-1β, interleukin-6, TNF-α and CRP respectively (P > 0.05). Finally, no effect of ARBs was found when comparing participants who received ARBs throughout the 5.4-year follow-up with participants on other antihypertensive drugs: OR and (95% CI) of 0.93 (0.61-1.42), 0.80 (0.54-1.17), 0.86 (0.59-1.25) and 0.95 (0.67-1.35) for interleukin-1β, interleukin-6, TNF-α and CRP respectively (P > 0.05). CONCLUSION: ARBs are not associated with reduced levels of inflammatory markers in the general population.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

Markers of iron metabolism and metabolic syndrome in Swiss adults

Plusieurs études populationnelles ont montré l'existence d'une association entre des taux sanguins élevés de transferrine et le syndrome métabolique (SM). Bien que cette association soit bien établie, restent encore à être décrites les associations entre le SM et les autres marqueurs sanguins du métabolisme du fer, tels que le fer, la transferrine (Tsf), la capacité totale de fixation de la transferrine (CTF) ou la saturation de la transferrine (SaTsf) sanguins. Le but de notre étude a été d'identifier les associations entre les différents marqueurs du métabolisme du fer (fer, ferritine, Tsf, CTF et SaTsf) et le SM. Les données de l'étude CoLaus, récoltées entre 2003 et 2006, ont été utilisées. Le SM était défini selon les critères du National Cholesterol Education Program Adult Panel III. L'analyse statistique a été faite en stratifiant selon le genre ainsi que le status ménopausal chez les femmes. Des 6733 participants, 1235 (18%) ont été exclus de fait d'absence de données concernant les variables qui nous intéressaient, ou chez qui nous avons soupçonné une possible hémochromatose non diagnostiquée (SaTsf> 50%). Des 5498 participants restant (âge moyen ± écart-type: 53 ± 11 ans), 2596 étaient des hommes, 1285 des femmes pré- et 1617 des femmes postménopausées. La prévalence du SM était de 29,4% chez les hommes, 8,3% et 25,5% chez les femmes pré- et postménopausées, respectivement. Dans les trois groupes, la prévalence du SM était la plus haute dans les quartiles les plus élevés de ferritine, Tsf et CTF, ainsi que dans le quartile le plus bas de SaTsf. Après ajustement sur l'âge, l'indice de masse corporelle, la protéine C réactive, la consommation de tabac et/ou d'alcool, la prise de suppléments en fer et les marqueurs hépatiques, l'appartenance au quartile le plus élevé de ferritine, Tsf ou CTF était associée à un risque plus important de SM chez les hommes et les femmes postménopausées : Odds ratio (OR) et [intervalle de confiance à 95%] pour la ferritine 1.44 [1.07-1.94] et 1.47 [0.99-2.17]; pour la Tsf et la CTF, OR=1.43 [1.06-1.91] et 2.13 [1.44-3.15] pour les hommes et les femmes postménopausées, respectivement. Au contraire, l'appartenance au quartile le plus élevé de la SaTsf était associé à un risque moins important de SM: OR=0.77 [0.57-1.05] et 0.59 [0.39-0.90] pour les hommes et les femmes postménopausées, respectivement. Il n'y avait aucune association entre les marqueurs sanguins du métabolisme du fer et le SM chez les femmes préménopausées, ni entre le fer sanguin et le SM chez les trois groupes. En conclusion, la majorité des marqueurs sanguins du métabolisme du fer, mais pas le fer lui-même, sont associés de manière indépendante au SM chez les hommes et les femmes postménopausées. -- Context: Excessive iron storage has been associated with metabolic syndrome (MS). Objective: To assess the association between markers of iron metabolism and MS in a healthy population. Design: Cross-sectional study conducted between 2003 and 2006. Setting: Population-based study in Lausanne, Switzerland. Patients: 5,498 participants aged 35-75 years, stratified by sex and menopausal status. Participants with transferrin saturation (TSAT) >50% were excluded. Intervention: None. Main Outcome Measures: serum iron, ferritin, transferrin, total iron binding capacity (TIBC) and TSAT. MS was defined according to ATP-III criteria. Results: Prevalence of MS was 29.4% in men, 8.3% in premenopausal and 25.5% in postmenopausal women. On bivariate analysis, the highest prevalence of MS occurred in the highest quartiles of serum ferritin, transferrin and TIBC, and in the lowest quartile of TSAT. After multivariate adjustment for age, body mass index, C-reactive protein, smoking, alcohol, liver markers and iron supplementation, men and postmenopausal women in the highest quartile of serum ferritin, transferrin and TIBC had a higher risk of presenting with MS: for ferritin, Odds ratio and [95% CI]=1.44 [1.07-1.94] for men and 1.47 [0.99-2.17] for postmenopausal women; for transferrin and TIBC, OR=1.43 [1.06-1.91] and 2.13 [1.44-3.15], Participants in the highest quartile of TSAT had a lower risk of MS: OR=0.77 [0.57-1.05] for men and 0.59 [0.39-0.90] for postmenopausal women. No association was found between iron and MS and between markers of iron metabolism and MS in premenopausal women. Conclusion: Ferritin, transferrin, TIBC are positively and TSAT is negatively associated with MS in men and postmenopausal women.

Combining conservative and variable markers to inferthe evolutionary history of Prunus subgen. Amygdalus s.l.under domestication

The genus Prunus L. is large and economically important. However, phylogenetic relationships within Prunus at low taxonomic level, particularly in the subgenus Amygdalus L. s.l., remain poorly investigated. This paper attempts to document the evolutionary history of Amygdalus s.l. and establishes a temporal framework, by assembling molecular data from conservative and variable molecular markers. The nuclear s6pdh gene in combination with the plastid trnSG spacer are analyzed with bayesian and maximum likelihood methods. Since previous phylogenetic analysis with these markers lacked resolution, we additionally analyzed 13 nuclear SSR loci with the δµ2 distance, followed by an unweighted pair group method using arithmetic averages algorithm. Our phylogenetic analysis with both sequence and SSR loci confirms the split between sections Amygdalus and Persica, comprising almonds and peaches, respectively. This result is in agreement with biogeographic data showing that each of the two sections is naturally distributed on each side of the Central Asian Massif chain. Using coalescent based estimations, divergence times between the two sections strongly varied when considering sequence data only or combined with SSR. The sequence-only based estimate (5 million years ago) was congruent with the Central Asian Massif orogeny and subsequent climate change. Given the low level of differentiation within the two sections using both marker types, the utility of combining microsatellites and data sequences to address phylogenetic relationships at low taxonomic level within Amygdalus is discussed. The recent evolutionary histories of almond and peach are discussed in view of the domestication processes that arose in these two phenotypically-diverging gene pools: almonds and peaches were domesticated from the Amygdalus s.s. and Persica sections, respectively. Such economically important crops may serve as good model to study divergent domestication process in close genetic pool.

Understanding oceanic migrations with intrinsic biogeochemical markers

Migratory marine vertebrates move annually across remote oceanic water masses crossing international borders. Many anthropogenic threats such as overfishing, bycatch, pollution or global warming put millions of marine migrants at risk especially during their long-distance movements. Therefore, precise knowledge about these migratory movements to understand where and when these animals are more exposed to human impacts is vital for addressing marine conservation issues. Because electronic tracking devices suffer from several constraints, mainly logistical and financial, there is emerging interest in finding appropriate intrinsic markers, such as the chemical composition of inert tissues, to study long-distance migrations and identify wintering sites. Here, using tracked pelagic seabirds and some of their own feathers which were known to be grown at different places and times within the annual cycle, we proved the value of biogeochemical analyses of inert tissue as tracers of marine movements and habitat use. Analyses of feathers grown in summer showed that both stable isotope signatures and element concentrations can signal the origin of breeding birds feeding in distinct water masses. However, only stable isotopes signalled water masses used during winter because elements mainly accumulated during the long breeding period are incorporated into feathers grown in both summer and winter. Our findings shed new light on the simple and effective assignment of marine organisms to distinct oceanic areas, providing new opportunities to study unknown migration patterns of secretive species, including in relation to human-induced mortality on specific populations in the marine environment.

Subfamilial and tribal relationships of Ranunculaceae: evidence from eight molecular markers

The first molecular phylogenies of the flowering plant family Ranunculaceae were published more than twenty years ago, and have led to major changes in the infrafamilial classification. However, the current phylogeny is not yet well supported, and relationships among subfamilies and tribes of Ranunculaceae remain an open question. Eight molecular markers from the three genomes (nuclear, chloroplast and mitochondrial) were selected to investigate these relationships, including new markers for the family (two homologs of the nuclear CYCLOIDEA gene, the chloroplast gene ndhF, and the mitochondrial intron nad4-I1). The combination of multiple markers led to better resolution and higher support of phylogenetic relationships among subfamilies of Ranunculaceae, and among tribes within subfamily Ranunculoideae. Our results challenge the monophyly of Ranunculoideae as currently circumscribed due to the position of tribe Adonideae (Ranunculoideae), sister to Thalictroideae. We suggest that Thalictroideae could be merged with Ranunculoideae in an enlarged single subfamily.

Trace me if you can: the use of intrinsic biogeochemical markers in marine top predators

Human activities have serious impacts on marine apex predators. Inadequate knowledge of the spatial and trophic ecology of these marine animals ultimately compromises the viability of their populations and impedes our ability to use them as environmental biomonitors. Intrinsic biogeochemical markers, such as stable isotopes, fatty acids, trace elements, and chemical pollutants, are increasingly being used to trace the spatial and trophic ecology of marine top predators. Notable advances include the emergence of the first oceanographic"isoscapes" (isotopic geographic gradients), the advent of compound-specific isotopic analyses, improvements in diet reconstruction through Bayesian statistics, and tissue analysis of tracked animals to ground-truth biogeochemical profiles. However, most researchers still focus on only a few tracers. Moreover, insufficient knowledge of the biogeochemical integration in tissues, fractionation and routing processes, and geographic and temporal variability in baseline levels continue to hamper the resolution and potential of these markers in studying the spatial and feeding ecology of top predators.

Different Plasma Markers of Inflammation Are Influenced by Immune Recovery and cART Composition or Intensification in Treated HIV Infected Individuals

Abstract Background HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Methods Longitudinal plasma samples (0–48 weeks) from the IntegRal (n = 67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts<350 cells/µl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. Results At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P = 0.040). Conclusions The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.

Exposure to Tobacco Smoke and Markers of Subclinical Atherosclerosis in Children and Adolescents. The STRIP Study.

Background: Measurement of serum cotinine, a major metabolite of nicotine, provides a valid marker for quantifying exposure to tobacco smoke. Exposure to tobacco smoke causes vascular damage by multiple mechanisms, and it has been acknowledged as a risk factor for atherosclerosis. Multifactorial atherosclerosis begins in childhood, but the relationship between exposure to tobacco smoke and arterial changes related to early atherosclerosis have not been studied in children. Aims: The aim of the present study was to evaluate exposure to tobacco smoke with a biomarker, serum cotinine concentration, and its associations with markers of subclinical atherosclerosis and lipid profile in school-aged children and adolescents. Subjects and Methods: Serum cotinine concentration was measured using a gas chromatographic method annually between the ages 8 and 13 years in 538-625 children participating since infancy in a randomized, prospective atherosclerosis prevention trial STRIP (Special Turku coronary Risk factor Intervention Project). Conventional atherosclerosis risk factors were measured repeatedly. Vascular ultrasound studies were performed among 402 healthy 11-year-old children and among 494 adolescents aged 13 years. Results: According to serum cotinine measurements, a notable number of the school aged children and adolescents were exposed to tobacco smoke, but the exposure levels were only moderate. Exposure to tobacco smoke was associated with decreased endothelial function as measured with flow-mediated dilation of the brachial artery, decreased elasticity of the aorta, and increased carotid and aortic intima-media thickness. Longitudinal exposure to tobacco smoke was also related with increased apolipoprotein B and triglyceride levels in 13-year-old adolescents, whose body mass index and nutrient intakes did not differ. Conclusions: These findings suggest that exposure to tobacco smoke in childhood may play a significant role in the development of early atherosclerosis. Key Words: arterial elasticity, atherosclerosis, children, cotinine, endothelial function, environmental tobacco smoke, intima-media thickness, risk factors, ultrasound