Culture-induced changes in blood-brain barrier transcriptome: implications for amino-acid transporters in vivo

Tight homeostatic control of brain amino acids (AA) depends on transport by solute carrier family proteins expressed by the blood-brain barrier (BBB) microvascular endothelial cells (BMEC). To characterize the mouse BMEC transcriptome and probe culture-induced changes, microarray analyses of platelet endothelial cell adhesion molecule-1-positive (PECAM1(+)) endothelial cells (ppMBMECs) were compared with primary MBMECs (pMBMEC) cultured in the presence or absence of glial cells and with b.End5 endothelioma cell line. Selected cell marker and AA transporter mRNA levels were further verified by reverse transcription real-time PCR. Regardless of glial coculture, expression of a large subset of genes was strongly altered by a brief culture step. This is consistent with the known dependence of BMECs on in vivo interactions to maintain physiologic functions, for example, tight barrier formation, and their consequent dedifferentiation in culture. Seven (4F2hc, Lat1, Taut, Snat3, Snat5, Xpct, and Cat1) of nine AA transporter mRNAs highly expressed in freshly isolated ppMBMECs were strongly downregulated for all cultures and two (Snat2 and Eaat3) were variably regulated. In contrast, five AA transporter mRNAs with low expression in ppMBMECs, including y(+)Lat2, xCT, and Snat1, were upregulated by culture. We hypothesized that the AA transporters highly expressed in ppMBMECs and downregulated in culture have a major in vivo function for BBB transendothelial transport.

Indirectly measuring evaluations of several attitude objects in relation to a neutral reference point

This article presents a new response time measure of evaluations, the Evaluative Movement Assessment (EMA). Two properties are verified for the first time in a response time measure: (a) mapping of multiple attitude objects to a single scale, and (b) centering that scale around a neutral point. Property (a) has implications when self-report and response time measures of attitudes have a low correlation. A study using EMA as an indirect measure revealed a low correlation with self-reported attitudes when the correlation reflected between-subjects differences in preferences for one attitude object to a second. Previously this result may have been interpreted as dissociation between two measures. However, when correlations from the same data reflected within-subject preference rank orders between multiple attitude objects, they were substantial (average r = .64). This result suggests that the presence of low correlations between self-report and response time measures in previous studies may be a reflection of methodological aspects of the response time measurement techniques. Property (b) has implications for exploring theoretical questions that require assessment of whether an evaluation is positive or negative (e.g., prejudice), because it allows such classifications in response time measurement to be made for the first time.

Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors

AIMS Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. METHODS AND RESULTS We combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. CONCLUSION We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.

Draft Genome Sequence of the Virulent Clostridium chauvoei Reference Strain JF4335

Clostridium chauvoei is the etiological agent of blackleg, a disease of cattle and sheep with high mortality rates, causing severe economic losses in livestock production. Here, we report the draft genome sequence of the virulent C. chauvoei strain JF4335 (2.8 Mbp and 28% G+C content) and the annotation of the genome.

SLR-derived terrestrial reference frame using the observations to LAGEOS-1/2, Starlette, Stella, and AJISAI

Currently, the contributions of Starlette, Stella, and AJISAI are not taken into account when defining the International Terrestrial Reference Frame (ITRF), despite the large amount of data collected in a long time-span. Consequently, the SLR-derived parameters and the SLR part of the ITRF are almost exclusively defined by LAGEOS-1 and LAGEOS-2. We investigate the potential of combining the observations to several SLR satellites with different orbital characteristics. Ten years of SLR data are homogeneously processed using the development version 5.3 of the Bernese GNSS Software. Special emphasis is put on orbit parameterization and the impact of LEO data on the estimation of the geocenter coordinates, Earth rotation parameters, Earth gravity field coefficients, and the station coordinates in one common adjustment procedure. We find that the parameters derived from the multi-satellite solutions are of better quality than those obtained in single satellite solutions or solutions based on the two LAGEOS satellites. A spectral analysis of the SLR network scale w.r.t. SLRF2008 shows that artifacts related to orbit perturbations in the LAGEOS-1/2 solutions, i.e., periods related to the draconitic years of the LAGEOS satellites, are greatly reduced in the combined solutions.

A robust reference signal generator for synchronized ventricular assist devices

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.

Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

The Forensic Reference Phantom-a new tool for quality assurance of attenuation measurements in forensic radiology

Introduction The purpose of this paper is to present the technical specifications of the Forensic Reference Phantom (FRP), to test its behavior relative to organic test materials, and discuss potential applications of the phantom in forensic radiology. Materials and method The FRP prototype is made of synthetic materials designed to simulate the computed tomography (CT) attenuation of water. It has six bore holes that accommodate multiuse containers. These containers were filled with test materials and scanned at 80 kVp, 120 kVp, and 140 kVp. X-ray attenuation was measured by two readers. Intra- and inter-reader reliability was assessed using the intra-class correlation coefficient (ICC). Significance levels between mean CT numbers at 80 kVp, 120 kVp, and 140 kVp were assessed with the Friedman-test. The T-test was used to assess significance levels between the FRP and water. Results Overall mean CT numbers ranged from −3.0–3.7HU for the FRP; −1000.3–−993.5HU for air; −157.7– −108.1HU for oil; 35.5–42.0HU for musle tissue; and 1301.5–2354.8HU for cortical bone. Inter-reader and intra-reader reliability were excellent (ICC>0.994; and ICC=0.999 respectively). CT numbers were significantly different at different energy levels. There was no significant difference between the attenuation of the FRP and water. Conclusions The FRP is a new tool for quality assurance and research in forensic radiology. The mean CT attenuation of the FRP is equivalent to water. The phantom can be scanned during routine post-mortem CT to assess the composition of unidentified objects. In addition, the FRP may be used to investigate new imaging algorithms and scan protocols in forensic radiology.