Novel ageing-biomarker discovery using data-intensive technologies

Ageing is accompanied by many visible characteristics. Other biological and physiological markers are also well-described e.g. loss of circulating sex hormones and increased inflammatory cytokines. Biomarkers for healthy ageing studies are presently predicated on existing knowledge of ageing traits. The increasing availability of data-intensive methods enables deep-analysis of biological samples for novel biomarkers. We have adopted two discrete approaches in MARK-AGE Work Package 7 for biomarker discovery; (1) microarray analyses and/or proteomics in cell systems e.g. endothelial progenitor cells or T cell ageing including a stress model; and (2) investigation of cellular material and plasma directly from tightly-defined proband subsets of different ages using proteomic, transcriptomic and miR array. The first approach provided longitudinal insight into endothelial progenitor and T cell ageing.This review describes the strategy and use of hypothesis-free, data-intensive approaches to explore cellular proteins, miR, mRNA and plasma proteins as healthy ageing biomarkers, using ageing models and directly within samples from adults of different ages. It considers the challenges associated with integrating multiple models and pilot studies as rational biomarkers for a large cohort study. From this approach, a number of high-throughput methods were developed to evaluate novel, putative biomarkers of ageing in the MARK-AGE cohort

Morphologic study of the pancreas of young and adults alpacas (Vicugna pacos)

El objetivo de este estudio fue realizar una caracterización morfológica del páncreas de alpacas jóvenes (n=9) y adultas (n=5). Para el estudio macroscópico se observó el páncreas in situ reconociendo su forma y relación con otros órganos. Para el estudio microscópico se realizaron cortes histológicos de 5 μm de espesor tiñendo las láminas con hematoxilina de Mayer-Eosina y tricrómico de Masson. El páncreas se divide en tres secciones: cuerpo, lóbulo derecho y lóbulo izquierdo. El lóbulo izquierdo se extiende hacia el plano izquierdo llegando a colindar con el bazo y en mayor proporción al colon descendente. El conducto hepatopancreático presentó dos orígenes: uno donde el conducto hepático se introduce en el parénquima pancreático y lo abandona por el lóbulo derecho como conducto hepatopancreático, y otro donde el conducto pancreático se une con el hepático al emerger del lóbulo derecho para formar el conducto hepatopancreático. En la microscopía se apreció que el parénquima pancreático se encuentra rodeado por una fina capa de tejido conectivo formada en su mayoría por fibras colágenas, que se invaginan dentro del parénquima formando lóbulos y pseudolóbulos, así como células con forma piramidal acomodadas en forma de acinos. Dentro del parénquima se observaron los islotes de Langerhans distribuidos al azar. Los conductos intralobulares e interlobulares se encuentran conformados por epitelio cubico simple, y el conducto hepatopancreático está conformado por una extensa mucosa irregular tapizada de epitelio columnar con microvellosidades. Se concluye que el páncreas de la alpaca muestra diferencias morfológicas con otras especies como rumiantes, herbívoros y carnívoros domésticos.The aim of this study was to morphologically characterize the pancreas of young (n=9) and adult (n=5) alpacas. In the macroscopic study, the pancreas was observed in situ to determine the shape and its relationship with other organs. In the microscopic study, routine histologic procedures were applied and histological sections of 5 μm thick were stained with Mayer-Eosin hematoxylin and Masson trichrome. The pancreas is divided in three sections: body, right lobe and left lobe which extend to the left plane, bordering the spleen and in greater proportion to the descendant colon. The hepatopancreatic duct presented two origins; one where the hepatic duct enters the pancreatic parenchyma and it leaves by the right lobe as the hepatopancreatic duct and another where the pancreatic duct joins with the hepatic duct as it emerges from the right lobe to form the hepatopancreatic duct. In the microscopic evaluation was observed that the pancreatic parenchyma is surrounded by a thin layer of connective tissue formed mostly by collagen fibers, which invaginate within the parenchyma forming lobes and pseudolobules, as well as cells with pyramidal shape accommodated in the form of acini. In the parenchyma was observed the islets of Langerhans randomly distributed. The intralobular and interlobular ducts were formed by simple cubic epithelium, and the hepatopancreatic duct was formed by an extensive irregular mucosa covered with columnar epithelium with microvilli. It is concluded that the alpaca pancreas shows morphological differences with other species such as ruminants, herbivores and domestic carnivores

Selection on Visual Opsin Genes in Diurnal Neotropical Frogs and Loss of the SWS2 Opsin in Poison Frogs

Amphibians are ideal for studying visual system evolution because their biphasic (aquatic and terrestrial) life history and ecological diversity expose them to a broad range of visual conditions. Here, we evaluate signatures of selection on visual opsin genes across Neotropical anurans and focus on three diurnal clades that are well-known for the concurrence of conspicuous colors and chemical defense (i.e., aposematism): poison frogs (Dendrobatidae), Harlequin toads (Bufonidae: Atelopus), and pumpkin toadlets (Brachycephalidae: Brachycephalus). We found evidence of positive selection on 44 amino acid sites in LWS, SWS1, SWS2, and RH1 opsin genes, of which one in LWS and two in RH1 have been previously identified as spectral tuning sites in other vertebrates. Given that anurans have mostly nocturnal habits, the patterns of selection revealed new sites that might be important in spectral tuning for frogs, potentially for adaptation to diurnal habits and for color-based intraspecific communication. Furthermore, we provide evidence that SWS2, normally expressed in rod cells in frogs and some salamanders, has likely been lost in the ancestor of Dendrobatidae, suggesting that under low-light levels, dendrobatids have inferior wavelength discrimination compared to other frogs. This loss might follow the origin of diurnal activity in dendrobatids and could have implications for their behavior. Our analyses show that assessments of opsin diversification in across taxa could expand our understanding of the role of sensory system evolution in ecological adaptation.</p

Fibre-optic SPR sensor with a FBG interrogation scheme for readout enhancement

In this work a new configuration of a refractometric sensor for aqueous solutions based on the combination of surface plasmon resonance (SPR) with fibre Bragg gratings (FBG) is presented. Two FBGs are selected having reflection maxima in each side of the plasmon resonance peak. These FBGs enable a different processing scheme for the information provided by the SPR transducer. This improved interrogation method increases the sensitivity and resolution of the sensor compared with those obtained with the usual method of tracking the spectral transmittance minimum and makes the system performance independent of optical source power fluctuations. The experimental results obtained with a double-layer uniform-waist tapered fibre show the feasibility of this approach and its applicability in SPR-based biosensors that must face very exigent measuring conditions

Negative Impacts of Human Land Use on Dung Beetle Functional Diversity

The loss of biodiversity caused by human activity is assumed to alter ecosystem functioning. However our understanding of the magnitude of the effect of these changes on functional diversity and their impact on the dynamics of ecological processes is still limited. We analyzed the functional diversity of copro-necrophagous beetles under different conditions of land use in three Mexican biosphere reserves. In Montes Azules pastures, forest fragments and continuous rainforest were analyzed, in Los Tuxtlas rainforest fragments of different sizes were analyzed and in Barranca de Metztitlán two types of xerophile scrub with different degrees of disturbance from grazing were analyzed. We assigned dung beetle species to functional groups based on food relocation, beetle size, daily activity period and food preferences, and as measures of functional diversity we used estimates based on multivariate methods. In Montes Azules functional richness was lower in the pastures than in continuous rainforest and rainforest fragments, but fragments and continuous forest include functionally redundant species. In small rainforest fragments (<5 ha) in Los Tuxtlas, dung beetle functional richness was lower than in large rainforest fragments (>20 ha). Functional evenness and functional dispersion did not vary among habitat types or fragment size in these reserves. In contrast, in Metztitlán, functional richness and functional dispersion were different among the vegetation types, but differences were not related to the degree of disturbance by grazing. More redundant species were found in submontane than in crassicaule scrub. For the first time, a decrease in the functional diversity in communities of copro-necrophagous beetles resulting from changes in land use is documented, the potential implications for ecosystem functioning are discussed and a series of variables that could improve the evaluation of functional diversity for this biological group is proposed

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented