131 research outputs found

    In situ biomonitoring shows seasonal patterns and environmentally mediated gaping activity in the bivalve, Pinna nobilis

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    The rhythms and responses of animals to environmental factors are important issues for their adaptation to natural cycles. These rhythms assure an optimum synchrony between organisms and their environment. Bio-logging enables monitoring these activity cycles remotely. To characterize rhythms and responses of fan mussels (Pinna nobilis) to environmental factors, six individuals were monitored from April 2009 to October 2011. The study was conducted at a station in the western Mediterranean at 11 m depth in Tabarca Island Marine Reserve (Alicante, Spain). Sensors at the station monitored dissolved oxygen (mg l−1), turbidity (ntu), temperature (°C), chlorophyll a concentration (chl a) (mg m−3), current speed (cm s−1), and direction (°). One pattern of gaping activity (P1) occurred from mid-July–early August–early November, whereas another pattern (P2) occurred the rest of the time (i.e., from early November–mid-July–early August). The activity was synchronized among the fan mussels and showed autocorrelation peaks at a period of 21.9–24 h. In P1, the fan mussels opened their valves according to the position and illumination of the sun and moon. In P2, however, individuals did not track sun and moonlight, although their gaping activity was regular and synchronized. Likewise, individuals were unaffected by high-frequency (daily) variation in dissolved oxygen and (chl a). Gaping activity was directly influenced by current intensity and direction. The shift between the two patterns and the presence of similar periods of autocorrelation in the activity time series indicate that P. nobilis has an internal clock

    Cardiovascular risk of metabolically healthy obesity in two european populations: Prevention potential from a metabolomic study

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    Background: A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern. Methods: This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25-30, ≥ 30 kg/m2). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events. Results: Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7-13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73-6.28] for normal weight, 2.50 [95% CI: 1.34-4.66] for overweight, and 3.42 [95% CI: 1.81-6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36-3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10-1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91). Conclusions: Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention.The work was supported by Internal Funds KU Leuven (STG-18-00379), the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT), the Ministerio de Ciencia e Innovación of Spain (PID2019-108973RB-C21 and C22 and PCIN2017-117), the Generalitat Valenciana of Spain (GV/2020/048), and GUTMOM (INTIMIC-085) from the EU Joint Programming Initiative Healthy Diet Healthy Life (HDHL).S

    LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

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    The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. Methods: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. Results: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ± 3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. Conclusions: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD

    Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism

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    OBJECTIVE: To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. DESIGN: To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). RESULTS: Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. CONCLUSIONS: Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans

    Magnetic resonance microscopy and correlative histopathology of the infarcted heart

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    Altres ajuts:The present study was supported by the EU Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI HDHL INTIMIC-085), Generalitat Valenciana (GV/2018/116), INCLIVA and Universitat de Valencia (program VLC-BIOCLINIC 20-nanomIRM-2016A).Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI

    Handling method alters the hedonic value of reward in laboratory mice

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    Mice are the most widely used model species for drug discovery and scientific research. Consequently, it is important to refine laboratory procedures and practices to ensure high standards of welfare and scientific data quality. Recent studies have identified that the standard practice of handling laboratory mice by their tails increases behaviours indicative of anxiety, which can be overcome by handling mice using a tunnel. However, despite clear negative effects on mice’s behaviour, tunnel handling has yet to be widely implemented. In this study, we provide the first evidence that tail handling also reduces mice’s responses to reward. Anhedonia is a core symptom of clinical depression, and is measured in rodents by assessing how they consume a sucrose solution: depressed mice consume less sucrose and the size of their licking bouts when drinking (their ‘lick cluster sizes’) also tend to be smaller. We found that tail handled mice showed more anhedonic responses in both measures compared to tunnel handled mice, indicative of a decreased responsiveness to reward and potentially a more depressive-like state. Our findings have significant implications for the welfare of laboratory mice as well as the design and interpretation of scientific studies, particularly those investigating or involving reward

    A longitudinal study of environmental tobacco smoke exposure in children: Parental self reports versus age dependent biomarkers

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    <p>Abstract</p> <p>Background</p> <p>Awareness of the negative effects of smoking on children's health prompted a decrease in the self-reporting of parental tobacco use in periodic surveys from most industrialized countries. Our aim is to assess changes between ETS exposure at the end of pregnancy and at 4 years of age determined by the parents' self-report and measurement of cotinine in age related biological matrices.</p> <p>Methods</p> <p>The prospective birth cohort included 487 infants from Barcelona city (Spain). Mothers were asked about maternal and household smoking habit. Cord serum and children's urinary cotinine were analyzed in duplicate using a double antibody radioimmunoassay.</p> <p>Results</p> <p>At 4 years of age, the median urinary cotinine level in children increased 1.4 or 3.5 times when father or mother smoked, respectively. Cotinine levels in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 19.7 ng/ml; 95% CI 16.83–23.01) and exposed homes (GM 7.1 ng/ml; 95% CI 5.61–8.99) compared with non-exposed homes (GM 4.5 ng/ml; 95% CI 3.71–5.48). Maternal self-reported ETS exposure in homes declined in the four year span between the two time periods from 42.2% to 31.0% (p < 0.01). Nevertheless, most of the children considered non-exposed by their mothers had detectable levels of cotinine above 1 ng/mL in their urine.</p> <p>Conclusion</p> <p>We concluded that cotinine levels determined in cord blood and urine, respectively, were useful for categorizing the children exposed to smoking and showed that a certain increase in ETS exposure during the 4-year follow-up period occurred.</p

    Expression of TNF-related apoptosis-inducing ligand (TRAIL) in keratinocytes mediates apoptotic cell death in allogenic T cells

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    The objective of the present study was to evaluate the aptitude of TRAIL gene expression for inducing apoptosis in co-cultivated T-cells. This should allow preparing a strategy for the development of a durable, allogenic skin substitute based on the induction of an immune-privileged transplant. In order to counteract the significant potential of rejection in transplanted allogenic keratinocytes, we created a murine keratinocyte cell line which expressed TRAIL through stable gene transfer. The exogenic protein was localized on the cellular surface and was not found in soluble condition as sTRAIL. Contact to TRAIL expressing cells in co-culture induced cell death in sensitive Jurkat-cells, which was further intensified by lymphocyte activation. This cytotoxic effect is due to the induction of apoptosis. We therefore assume that the de-novo expression of TRAIL in keratinocytes can trigger apoptosis in activated lymphocytes and thus prevent the rejection of keratinocytes in allogenic, immune-privileged transplants
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