Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes

Breakdown of the inner blood-retinal barrier (iBRB) occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME) as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs) forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ) integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3) in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT) mice and in Gal-3(-/-) transgenic mice. Blood glucose was monitored and AGE levels were quantified by ELISA and immunohistochemistry. The diabetic groups were subdivided, and one group was treated with the AGE-inhibitor pyridoxamine (PM) while separate groups of WT and Gal-3(-/-) mice were maintained as nondiabetic controls. iBRB integrity was assessed by Evans blue assay alongside visualisation of TJ protein complexes via occludin-1 immunolocalization in retinal flat mounts. Retinal expression levels of the vasopermeability factor VEGF were quantified using real-time RT-PCR and ELISA. WT diabetic mice showed significant AGE -immunoreactivity in the retinal microvasculature and also showed significant iBRB breakdown (P < .005). These diabetics had higher VEGF mRNA and protein expression in comparison to controls (P < .01). PM-treated diabetics had normal iBRB function and significantly reduced diabetes-mediated VEGF expression. Diabetic retinal vessels showed disrupted TJ integrity when compared to controls, while PM-treated diabetics demonstrated near-normal configuration. Gal-3(-/-) mice showed significantly less diabetes-mediated iBRB dysfunction, junctional disruption, and VEGF expression changes than their WT counterparts. The data suggests an AGE-mediated disruption of iBRB via upregulation of VEGF in the diabetic retina, possibly modulating disruption of TJ integrity, even after acute diabetes. Prevention of AGE formation or genetic deletion of Gal-3 can effectively prevent these acute diabetic retinopathy changes.

The absence of creativity in Feist and the computational process

The decision of the U.S. Supreme Court in 1991 in Feist Publications, Inc. v. Rural Tel. Service Co. affirmed originality as a constitutional requirement for copyright. Originality has a specific sense and is constituted by a minimal degree of creativity and independent creation. The not original is the more developed concept within the decision. It includes the absence of a minimal degree of creativity as a major constituent. Different levels of absence of creativity also are distinguished, from the extreme absence of creativity to insufficient creativity. There is a gestalt effect of analogy between the delineation of the not original and the concept of computability. More specific correlations can be found within the extreme absence of creativity. "[S]o mechanical" in the decision can be correlated with an automatic mechanical procedure and clauses with a historical resonance with understandings of computability as what would naturally be regarded as computable. The routine within the extreme absence of creativity can be regarded as the product of a computational process. The concern of this article is with rigorously establishing an understanding of the extreme absence of creativity, primarily through the correlations with aspects of computability. The understanding established is consistent with the other elements of the not original. It also revealed as testable under real-world conditions. The possibilities for understanding insufficient creativity, a minimal degree of creativity, and originality, from the understanding developed of the extreme absence of creativity, are indicated. 

Transcriptional upregulation of SOCS 1 and suppressors of cytokine signaling 3 mRNA in the absence of suppressors of cytokine signaling 2 mRNA after infection with West Nile virus or tick-borne encephalitis virus.

Suppressors of cytokine signaling (SOCS) proteins are a family of proteins that are able to act in a classic negative feedback loop to regulate cytokine signal transduction. The regulation of the immune response by SOCS proteins may contribute to persistent infection or even a fatal outcome. In this study, we have investigated the induction of SOCS 1-3 after peripheral infection with West Nile virus (WNV) or tick-borne encephalitis virus (TBEV) in the murine model. We have shown that the cytokine response after infection of mice with WNV or TBEV induces an upregulation in the brain of mRNA transcripts for SOCS 1 and SOCS 3, but not SOCS 2. We hypothesize that SOCS proteins may play a role in limiting cytokine responses in the brain as a neuroprotective mechanism, which may actually enhance the ability of neuroinvasive viruses such as WNV and TBEV to spread and cause disease.

An Absence of Ghosts: cultural and theatrical translation in the British Reception of The Mysteries-Yiimimangaliso

Mark Dornford-May’s widely-acclaimed adaptation of the medieval English Chester “mystery” plays, The Mysteries-Yiimimangaliso, reveal the extent to which theatrical translation, if it is to be intelligible to audiences, risks trading in cultural stereotypes belonging to both source and target cultures. As a South African production of a medieval English theatrical tradition which subsequently plays to an English audience, The Mysteries-Yiimimangaliso enacts a number of disorientating forms of cultural translation. Rather than facilitating the transmission of challenging literary and dramatic traditions, The Mysteries-Yiimimangaliso reveals the extent to which translation, as a politically correct - and thus politically anaemic - act, can become an end in itself in a globalised Anglophone theatrical culture.

Transformation of vaterite into calcite in the absence and the presence of copper(II) species. Thermal analysis, IR and EPR study

The transformation of vaterite into calcite may be performed by heating in the presence and the absence of oxygen. Vaterite remains thermally stable until a calcination temperature of 450°C. It transforms progressively to calcite up to 500°C giving two exothermic peaks: 1) at 481°C due to the transformation of vaterite surface which is in contact with a small amount of calcite phase already formed with the time on the solid surface from the humidity atmosphere; 2) at 491°C due to the transformation of pure vaterite bulk. The calcite phase remains stable until 700°C. Above this temperature the formation of CaO is observed.

The Role of Work Group in Individual Sickness Absence Behavior

The purpose of our two-year follow-up study was to examine the effect of the social components of the work group, such as group absence norms and cohesion, on sickness absence behavior among individuals with varying attitudes toward work attendance. The social components were measured using a questionnaire survey, and data on sickness absence behavior were collected from the employers' records. The study population consisted of 19,306 Finnish municipal employees working in 1,847 groups (78% women). Multilevel Poisson regression modeling was applied. The direct effects of work group characteristics on sickness absence were mostly insignificant. In contrast, both of the social components of a work group had an indirect impact: The more tolerant the group absence norms (at both individual- and cross-level) and the lower the group cohesion (at the individual level), the more the absence behavior of an individual was influenced by his or her attitude toward work attendance. We conclude that work group moderates the extent to which individuals with a liberal attitude toward work attendance actually engage in sickness absence behavior.

Work-family characteristics as determinants of sickness absence: A large-scale cohort study of three occupational grades

This study examined the previously unexplored occupational grade-specific relationships of domestic responsibilities, the age of children, and work-family spillover, with registered sickness absence (>3 days' sick leave episodes, a mean follow-up of 17 months; n = 18,366 municipal employees; 76% women). The results showed that negative spillover from work into family life predicted a heightened rate of sickness absence spells among both women and men in all occupational categories (except upper white-collar men), but especially among blue-collar and lower white-collar employees. Furthermore, among all white-collar employees (except upper white-collar men), having young children (

Long hours in paid and domestic work and subsequent sickness absence: does control over daily working hours matter?

Objectives: To explore the associations of working hours ( paid, domestic, commuting, and total) with sickness absence, and to examine whether these associations vary according to the level of employee control over daily working hours.