Functional differences between the susceptibility Z−2/C−106 and protective Z+2/T−106 promoter region polymorphisms of the aldose reductase gene may account for the association with diabetic microvascular complications

AbstractStudies have shown that polymorphisms located at positions −106 and approximately −2100 base pairs (5′ALR2) in the regulatory region of the aldose reductase gene are associated with susceptibility to microvascular complications in patients with diabetes. The aim was to investigate the functional roles of these susceptibility alleles using an in vitro gene reporter assay. Susceptibility, neutral and protective 5′ALR2/−106 alleles were transfected into HepG2 cells and exposed to excess d-glucose (d-glucose at final concentrations 14 or 28 mmol/l). Transcriptional activities were determined using a dual luciferase reporter gene assay. The “susceptibility alleles” Z−2 with C−106 had the highest transcriptional activity when compared with the “protective” combination of Z+2 with C−106 alleles (58.7±9.9 vs. 10.1±0.7; P<0.0001). Those constructs with either the Z or Z−2 in combination with the C−106 allele had significantly higher transcriptional activities when compared to those with the T−106 allele (Z/C−106, 37.4±5.4 vs. Z/T−106 7.7±1.6, P<0.003; Z−2/C−106, 58.7±9.9 vs. Z−2/T−106 10.9±0.6, P<0.0001). These results demonstrate that the Z−2/C−106 haplotype is associated with elevated transcriptional activity of the aldose reductase gene. This in turn may explain the role of these polymorphisms in the susceptibility to diabetic microvascular complications

Towards insect inspired visual sensors for robots

Flying insects display a repertoire of complex behaviours that are facilitated by their non-standard visual system that if understood would offer solutions for weight- and power- constrained robotic platforms such as micro unmanned aerial vehicles (MUAVs). Crucial to this goal is revealing the specific features of insect eyes that engineered solutions would benefit from possessing, however progress in exploration of the design space has been limited by challenges in accurately replicating insect vision. Here we propose that emerging ray-tracing technologies are ideally placed to realise the high-fidelity replication of the insect visual perspective in a rapid, modular and adaptive framework allowing development of technical specifications for a new class of bio-inspired sensor. A proof-of-principle insect eye renderer is shown and insights into research directions it affords discussed

Asymmetric Induction in Intramolecular [2 + 2]-Photocycloadditions of 1,3-Disubstituted Allenes with Enones and Enoates

Irradiation of optically active allenes (89-92% ee) appended to enones and enoates affords alkylidenecyclobutane photoadducts with high levels of asymmetric induction (83-100%) derived exclusively from the allene fragment. The substrates studied include allenes tethered to enones such as 1,3-cyclohexanedionea nd 1,3-cyclopentanedione, as well as allenes tethered to functionalized coumarins. The enantiomer ratios of the photoadducts were quantified by derivatization of the products as the corresponding Mosher MTPA esters and analysis by ^1H NMR spectroscopy. The exo-methylenecyclobutanes obtained upon irradiation of allene-mumarins are isolated as single olefin diastereomers. Irradiation of a coumarin tethered at C(5) with an optically active allene affords an alkynyl-substituted oxepane with complete asymmetric induction

CompoundRay, an open-source tool for high-speed and high-fidelity rendering of compound eyes

Revealing the functioning of compound eyes is of interest to biologists and engineers alike who wish to understand how visually complex behaviours (e.g. detection, tracking, and navigation) arise in nature, and to abstract concepts to develop novel artificial sensory systems. A key investigative method is to replicate the sensory apparatus using artificial systems, allowing for investigation of the visual information that drives animal behaviour when exposed to environmental cues. To date, ‘compound eye models’ (CEMs) have largely explored features such as field of view and angular resolution, but the role of shape and overall structure have been largely overlooked due to modelling complexity. Modern real-time ray-tracing technologies are enabling the construction of a new generation of computationally fast, high-fidelity CEMs. This work introduces a new open-source CEM software (CompoundRay) that is capable of accurately rendering the visual perspective of bees (6000 individual ommatidia arranged on 2 realistic eye surfaces) at over 3000 frames per second. We show how the speed and accuracy facilitated by this software can be used to investigate pressing research questions (e.g. how low resolution compound eyes can localise small objects) using modern methods (e.g. machine learning-based information exploration)

Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma

Background: New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.Methods: CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.Results: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.Conclusions: Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment

The beta Pictoris association: Catalog of photometric rotational periods of low-mass members and candidate members

We intended to compile the most complete catalog of bona fide members and candidate members of the beta Pictoris association, and to measure their rotation periods and basic properties from our own observations, public archives, and exploring the literature. We carried out a multi-observatories campaign to get our own photometric time series and collected all archived public photometric data time series for the stars in our catalog. Each time series was analyzed with the Lomb-Scargle and CLEAN periodograms to search for the stellar rotation periods. We complemented the measured rotational properties with detailed information on multiplicity, membership, and projected rotational velocity available in the literature and discussed star by star. We measured the rotation periods of 112 out of 117 among bona fide members and candidate members of the beta Pictoris association and, whenever possible, we also measured the luminosity, radius, and inclination of the stellar rotation axis. This represents to date the largest catalog of rotation periods of any young loose stellar association. We provided an extensive catalog of rotation periods together with other relevant basic properties useful to explore a number of open issues, such as the causes of spread of rotation periods among coeval stars, evolution of angular momentum, and lithium-rotation connection.Comment: Forthcoming article, Received: 20 June 2016 / Accepted: 09 September 2016; 40 pages, 2 figures. The online figures A1-A73 are available at CD

Gender Specific Effects of Mood on Alcohol Seeking Behaviors: Preliminary Findings using Intravenous Alcohol Self-Administration

Background Although negative mood has long been implicated in differences in alcohol seeking by men and women, little research has used precise, well-controlled laboratory experiments to examine how negative mood affects alcohol-seeking behaviors. Methods A total of 34 (19 women) community-dwelling, alcohol-using adults aged 21 to 32 (mean age = 24.86, SD = 3.40, 74.3% Caucasian; Alcohol Use Disorders Identification Test [AUDIT] = 10.1, SD = 3.4) completed 2 counterbalanced intravenous alcohol self-administration sessions: one under negative mood and one under neutral mood. Fourteen individuals (9 women; mean age = 25.00, SD = 2.77) participated in an alcohol “liking” experiment (i.e., free access [FA] drinking) and 20 individuals (10 women; mean age = 24.77, SD = 3.73) participated in an alcohol “wanting” experiment, in which gaining access to alcohol required progressively effortful work. There was no significant difference between men and women on the AUDIT, t(32) = −0.38, p = 0.71. Results Priming with negative mood induction caused a significant decrease in self-reported mood (mean change = −1.85, t(32) = −6.81, p < 0.001), as intended. In FA, negative mood was associated with a significantly increased peak breath alcohol concentration (BrAC; F = 9.41, p = 0.01), with a trend toward a greater effect in men than in women (F = 2.67, p = 0.13). Negative mood also had a significant effect on peak BrAC achieved in the progressive work paradigm (F = 5.28, p = 0.04), with a significantly stronger effect in men (F = 5.35, p = 0.03) than women; men also trended toward more consistent work for alcohol across both neutral and negative sessions. Conclusions These preliminary findings demonstrate a gender-specific response on how mood affects alcohol seeking and suggest gender-specific interventions to prevent mood-based alcohol consumption

Human meniscus cells express hypoxia inducible factor-1α and increased SOX9 in response to low oxygen tension in cell aggregate culture

In previous work we demonstrated that the matrix-forming phenotype of cultured human cells from whole meniscus was enhanced by hypoxia (5% oxygen). Because the meniscus contains an inner region that is devoid of vasculature and an outer vascular region, here we investigate, by gene expression analysis, the separate responses of cells isolated from the inner and outer meniscus to lowered oxygen, and compared it with the response of articular chondrocytes. In aggregate culture of outer meniscus cells, hypoxia (5% oxygen) increased the expression of type II collagen and SOX9 (Sry-related HMG box-9), and decreased the expression of type I collagen. In contrast, with inner meniscus cells, there was no increase in SOX9, but type II collagen and type I collagen increased. The articular chondrocytes exhibited little response to 5% oxygen in aggregate culture, with no significant differences in the expression of these matrix genes and SOX9. In both aggregate cultures of outer and inner meniscus cells, but not in chondrocytes, there was increased expression of collagen prolyl 4-hydroxylase (P4H)α(I) in response to 5% oxygen, and this hypoxia-induced expression of P4Hα(I) was blocked in monolayer cultures of meniscus cells by the hypoxia-inducible factor (HIF)-1α inhibitor (YC-1). In fresh tissue from the outer and inner meniscus, the levels of expression of the HIF-1α gene and downstream target genes (namely, those encoding P4Hα(I) and HIF prolyl 4-hydroxylase) were significantly higher in the inner meniscus than in the outer meniscus. Thus, this study revealed that inner meniscus cells were less responsive to 5% oxygen tension than were outer meniscus cells, and they were both more sensitive than articular chondrocytes from a similar joint. These results suggest that the vasculature and greater oxygen tension in the outer meniscus may help to suppress cartilage-like matrix formation