LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.

The blood-brain barrier (BBB) is a term used to describe the unique properties of central nervous system (CNS) blood vessels. One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs). Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues. We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis. We further demonstrate that the BBB does not seal during embryogenesis in Lsr knockout mice with a leakage to small molecules. Finally, in mouse models in which BBB was disrupted, including an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and a middle cerebral artery occlusion (MCAO) model of stroke, LSR was down-regulated, linking loss of LSR and pathological BBB leakage

Medication adherence during adjunct therapy with statins and ACE inhibitors in adolescents with type 1 diabetes

OBJECTIVE: Suboptimal adherence to insulin treatment is a main issue in adolescents with type 1 diabetes. However, to date, there are no available data on adherence to adjunct noninsulin medications in this population. Our aim was to assess adherence to ACE inhibitors and statins and explore potential determinants in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS:There were 443 adolescents with type 1 diabetes recruited into the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and exposed to treatment with two oral drugs—an ACE inhibitor and a statin—as well as combinations of both or placebo for 2–4 years. Adherence was assessed every 3 months with the Medication Event Monitoring System (MEMS) and pill count. RESULTS: Median adherence during the trial was 80.2% (interquartile range 63.6–91.8) based on MEMS and 85.7% (72.4–92.9) for pill count. Adherence based on MEMS and pill count dropped from 92.9% and 96.3%, respectively, at the first visit to 76.3% and 79.0% at the end of the trial. The percentage of study participants with adherence ≥75% declined from 84% to 53%. A good correlation was found between adherence based on MEMS and pill count (r = 0.82, P < 0.001). Factors associated with adherence were age, glycemic control, and country. CONCLUSIONS: We report an overall good adherence to ACE inhibitors and statins during a clinical trial, although there was a clear decline in adherence over time. Older age and suboptimal glycemic control at baseline predicted lower adherence during the trial, and, predictably, reduced adherence was more prevalent in subjects who subsequently dropped out

Women We Loved: Paradoxes of public and private in the biographical television drama

Broadcast to critical acclaim and relatively large audiences for its niche channel, the Women We Loved season consisted of biographical dramatisations of three prominent female figures of 20th-century British culture. These dramas shared in common narratives that centre on the two aspects of ‘the public’ and ‘the private’: the tension between public career and personal life and the discrepancy between celebrity persona and private individual. Combining theoretical insights from feminist studies of biography with close textual analysis, this article analyses how performance, aesthetics and narrative express the ambivalent placement of their protagonists between public and private spheres

Zika virus impairs the development of blood vessels in a mouse model of congenital infection

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly

Eye tracking as an MT evaluation technique

Eye tracking has been used successfully as a technique for measuring cognitive load in reading, psycholinguistics, writing, language acquisition etc. for some time now. Its application as a technique for measuring the reading ease of MT output has not yet, to our knowledge, been tested. We report here on a preliminary study testing the use and validity of an eye tracking methodology as a means of semi-automatically evaluating machine translation output. 50 French machine translated sentences, 25 rated as excellent and 25 rated as poor in an earlier human evaluation, were selected. Ten native speakers of French were instructed to read the MT sentences for comprehensibility. Their eye gaze data were recorded non-invasively using a Tobii 1750 eye tracker. The average gaze time and fixation count were found to be higher for the “bad” sentences, while average fixation duration and pupil dilations were not found to be substantially different for output rated as good and output rated as bad. Comparisons between HTER scores and eye gaze data were also found to correlate well with gaze time and fixation count, but not with pupil dilation and fixation duration. We conclude that the eye tracking data, in particular gaze time and fixation count, correlate reasonably well with human evaluation of MT output but fixation duration and pupil dilation may be less reliable indicators of reading difficulty for MT output. We also conclude that eye tracking has promise as a semi-automatic MT evaluation technique, which does not require bi-lingual knowledge, and which can potentially tap into the end users’ experience of machine translation output

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Objectives: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. Methods: Twenty‐five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio‐Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes  3 mL/min/1.73m2/year, respectively), and albumin‐creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. Results: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor‐3, cystatin C, and beta‐2 microglobulin (B2M) (B coefficient[95%CI]: −0.19 [−0.27, −0.12], P = 7.0 × 10−7; −0.18 [−0.26, −0.11], P = 5.1 × 10−6; −0.12 [−0.20, −0.05], P = 1.6 × 10−3), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (−0.21 [−0.28, −0.14], P = 2.3 × 10−8) and cystatin C (−0.16 [−0.22, −0.09], P = 1.6 × 10−6). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10−6), whereas rapid increaser phenotype was associated with fibroblast growth factor‐23 (FGF‐23) (1.59 [1.23, 2.04], P = 2.6 × 10−4). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. Conclusions: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF‐23 was associated with eGFR increases, whereas trefoil factor‐3, cystatin C, and B2M were associated with baseline eGFR

Retinal Arteriolar Dilation Predicts Retinopathy in Adolescents With Type 1 Diabetes

OBJECTIVE—Alterations in retinal vascular caliber may reflect early subclinical microvascular dysfunction. In this study, we examined the association of retinal vascular caliber to incident retinopathy in young patients with type 1 diabetes