Role of Epac1 in pathogenesis of diabetic retinopathy

Poster Presentations - Theme 2published_or_final_version15th Research Postgraduate Symposium, Hong Kong, China, 1-2 December 2010. In Abstract - Poster Presentations of 15th Research Postgraduate Symposium, 2010, Theme II, p. 87 Abstract no. 1

Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy

Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions. To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion (tMCAO) was performed on Epac1-deficient (Epac1) mice, Epac2-deficient (Epac2) mice, and their wild type counterparts (Epac1+/+ and Epac2+/+). Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neuronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 (AQP4), glial fibrillary acidic protein (GFAP), peroxiredoxin 6 (Prx6) were observed in ipsilateral retinae. Epac2 ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2+/+. However, Epac1 ipsilateral retinae displayed similar pathology as those in Epac1+/+ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.published_or_final_versio

Helmets for preventing injury in motorcycle riders

Background: Motorcycle crash victims form a high proportion of those killed or injured in road traffic accidents. Injuries to the head, following motorcycle crashes, are a common cause of severe morbidity and mortality. It seems intuitive that helmets should protect against head injuries but it has been argued that motorcycle helmet use decreases rider vision and increases neck injuries. This review will collate the \u27current available evidence on helmets and their impact on mortality, and head, face and neck injuries following motorcycle crashes.Objectives: To quantify the effectiveness of wearing a motorcycle helmet in reducing mortality and head and neck injury following motorcycle crashes.Search strategy: Databases including the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1,2003), MEDLINE (January 1966 to February 2003), EMBASE (January 1985 to February 2003), CINAHL (January 1982 to February 2003), IRRD (International Road Research Documentation), TRANSDOC, TRIS (Transport Research Information Service), ATRI (Australian Transport Index) (1976 to Feb 2003), Science Citation Index were searched for relevant articles. Web sites of traffic and road accident research bodies including government agencies were also searched. Reference lists from topic reviews, identified studies and bibliographies were examined for relevant articles.Selection criteria: We considered for inclusion studies that investigated a population of motorcycle riders who had crashed, examining helmet use as an intervention and with outcomes that included one or more of the following: death, head, neck or facial injury. Studies included any that compared an intervention and control group and, therefore, included any randomised controlled trials, non-randomised controlled trials, cohort, case-control and cross-sectional studies. Ecological and case series studies were excluded.Data collection and analysis: Two reviewers independently screened reference lists for eligible articles. Two reviewers independently assessed articles for inclusion criteria. Data were abstracted by two independent reviewers using a standard abstraction form.Main results: Fifty-three observational studies were identified of varying quality. Despite methodological differences there was a remarkable consistency in results, particularly for mortality and head injury outcomes. Motorcycle helmets appear to reduce the risk of mortality although, due to heterogeneity in study design, an overall estimate of effect was not calculated. There was some evidence that the effect of helmets on mortality is modified by speed. Motorcycle helmets were found to reduce the risk of head injury and from five well-conducted studies the risk reduction is estimated to be 72% (OR 0.28, 95%CI 0.23,0.35). Insufficient evidence was found to estimate the effect of motorcycle helmets compared with no helmet on facial or neck injuries. However, studies of poorer quality suggest that helmets have no effect on the risk of neck injuries and are protective for facial injury. There was insufficient evidence to demonstrate whether differences in helmet type confer more or less advantage in injury reduction.Conclusions: Motorcycle helmets reduce the risk of mortality and head injury in motorcycle riders who crash, although the former effect may be modified by other crash factors such as speed. Further well-conducted research is required to determine the effects of helmets and different helmet types on mortalIty, head, neck and facial injuries. However, the findings suggest that global efforts to reduce road traffic injuries may be facilitated by increasing helmet use by motorcyclists.<br /

Impaired flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives: The effect of genetic loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia. © 2008 The Authors.published_or_final_versio

High index contrast photonic platforms for on-chip Raman spectroscopy

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively

Species composition, plant cover and diversity of recently reforested wild lands near Dabao Highway in Longitudinal Range-Gorge Region of Yunnan Province, China

Deforestation, over-cultivation and rural growth have severely damaged native vegetation of woodlands along roadsides in the Longitudinal Range-Gorge Region of Yunnan Province. This study wasconducted to evaluate the effect of different reforestation practices, which consisted of natural restoration or planting with tree seedlings that varied in species composition, coverage and diversity,on damaged roadside woodlands. Three randomly selected 10 m x 10 m plots in each reforestation practice were investigated. The results showed that the species composition, plant cover and speciesdiversity of the planted communities varied with reforestation strategies and time since planting. A higher number of species, proportion of native species and woody plants, canopy cover and speciesdiversity were found in naturally restored plots and in 3 - 4 year old plots that were planted with native plants. In the early stages of reforestation, herbs dominated the plant community in most plots, andwoody plants became more important with time after reforestation. Preliminary results suggest that plant height can be used an auxiliary indicator of plant cover to assess ecosystem function status ofthe restoration project. Also, evenness may be easier to restore than species richness. Natural restoration or reforestation with native dominant plants is a good management strategy for vegetationrestoration or improvement

Anti-proliferation Potential and Content of Fucoidan Extracted From Sporophyll of New Zealand Undaria Pinnatifida

Undaria pinnatifida is a species of brown seaweed known to contain rich amounts of fucoidan, a sulfated polysaccharide known to possess various biological activities. We isolated crude fucoidan (F0) from the sporophylls of U. pinnatifida grown in the Marlborough Sounds, New Zealand. Sulfate content, uronic acid content, and molecular weight of F0 were 15.02, 1.24, and >150 kDa, respectively. F0 was fractionated to yield three further fractions: F1, F2, and F3. Cytotoxicity of two major fractions was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The algal fucoidans specifically suppressed the proliferation of three cancer cell lines with less cytotoxicity against the normal cells. Selective cytotoxicity could relate to the distinctive structures of each fucoidan fraction. Results from this study provide evidence that fucoidan, especially from U. pinnatifida grown in New Zealand, possesses great potential to be used as a functional food to reduce cancer risk or supplement cancer treatment

Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback

 This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe effects of toxicant exposure on individuals captured in standard environmental risk assessments (ERA) do not necessarily translate proportionally into effects at the population-level. Population models can incorporate population resilience, physiological susceptibility, and likelihood of exposure, and can therefore be employed to extrapolate from individual- to population-level effects in ERA. Here, we present the development of an individual-based model (IBM) for the three-spined stickleback (Gasterosteus aculeatus) and its application in assessing population-level effects of disrupted male breeding behaviour after exposure to the anti-androgenic pesticide, fenitrothion. The stickleback is abundant in marine, brackish, and freshwater systems throughout Europe and their complex breeding strategy makes wild populations potentially vulnerable to the effects of endocrine disrupting chemicals (EDCs). Modelled population dynamics matched those of a UK field population and the IBM is therefore considered to be representative of a natural population. Literature derived dose-response relationships of fenitrothion-induced disruption of male breeding behaviours were applied in the IBM to assess population-level impacts. The modelled population was exposed to fenitrothion under both continuous (worst-case) and intermittent (realistic) exposure patterns and population recovery was assessed. The results suggest that disruption of male breeding behaviours at the individual-level cause impacts on population abundance under both fenitrothion exposure regimes; however, density-dependent processes can compensate for some of these effects, particularly for an intermittent exposure scenario. Our findings further demonstrate the importance of understanding life-history traits, including reproductive strategies and behaviours, and their density-dependence, when assessing the potential population-level risks of EDCs.Syngenta LtdBiotechnology and Biological Sciences Research Council (BBSRC

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth