Neuropilin-1 modulates p53/caspases axis to promote endothelial cell survival

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), one of the crucial pro-angiogenic factors, functions as a potent inhibitor of endothelial cell (EC) apoptosis. Previous progress has been made towards delineating the VPF/VEGF survival signaling downstream of the activation of VEGFR-2. Here, we seek to define the function of NRP-1 in VPF/VEGF-induced survival signaling in EC and to elucidate the concomitant molecular signaling events that are pivotal for our understanding of the signaling of VPF/VEGF. Utilizing two different in vitro cell culture systems and an in vivo zebrafish model, we demonstrate that NRP-1 mediates VPF/VEGF-induced EC survival independent of VEGFR-2. Furthermore, we show here a novel mechanism for NRP-1-specific control of the anti-apoptotic pathway in EC through involvement of the NRP-1-interacting protein (NIP/GIPC) in the activation of PI-3K/Akt and subsequent inactivation of p53 pathways and FoxOs, as well as activation of p21. This study, by elucidating the mechanisms that govern VPF/VEGF-induced EC survival signaling via NRP-1, contributes to a better understanding of molecular mechanisms of cardiovascular development and disease and widens the possibilities for better therapeutic targets.     

Rapid and dynamic regulation of TGF-beta receptors on blood vessels and fibroblasts during ischemia-reperfusion injury

Thepathophysiological mechanisms involved in ischemia-reperfusioninjury are poorly understood. Although transforming growth factor(TGF)- has been shown to provide protection againstischemia-reperfusion injury in different organ systems, littleis known about the regulation of TGF- action during this process.Here we analyzed the effect of ischemia and reperfusion on theexpression of TGF- and its receptors in vivo with a pig skin flapmodel. Analysis of unoperated skin, nonischemic control flap,ischemic flap, and reperfused flap by immunohistochemistryindicates that ischemia and reperfusion result in rapid anddynamic regulation of type I, II, and III TGF- receptors andTGF-1 in a cell type-specific manner. Furthermore, hypoxiaupregulates type II TGF- receptor mRNA in skin fibroblasts inculture. Together, our results reveal that TGF- receptors andTGF-1 are markedly increased under acute ischemic conditions in the blood vessels and fibroblasts of the skin. We conclude thatTGF- action is enhanced under ischemic conditions and that it may represent an adaptive response to ischemic injury. The augmented TGF- responsiveness may be a critical determinant of theprotective effect of TGF- during ischemia-reperfusion injury.

     

Successful management of retinal tear post-laser in situ keratomileusis retreatment

PURPOSE: To report a successful case management of a retinal tear post-Laser in situ Keratomileusis (LASIK) and retreatment. RESULTS: A patient with the history of ocular trauma underwent LASIK procedure for myopic astigmatism. Three months post-LASIK, she received additional excimer laser treatment for a symptomatic persistent central island. One month later; the patient experienced a flap tear at the edge of a prior chorioretinal scar. Retinal tear repair was successfully accomplished by indirect application of photocoagulation laser without damage to the corneal flap. CONCLUSIONS: To date, no definitive causal relationship has been established between retinal tear(s) and corneal refractive surgery. This report describes a retinal tear and repair, post-LASIK retreatment. The use of the indirect binocular argon laser alleviates the need to compress the LASIK flap and minimizes the potential for creating flap folds and striae, especially in the early post operative period. Clinicians should be on alert to consider this possible complication, post-LASIK and excimer laser; especially within a population whose clinical findings place them at greater risk.     

Site-Specific Cassette Exchange Systems in the Aedes aegypti Mosquito and the Plutella xylostella Moth

Genetically engineered insects are being evaluated as potential tools to decrease the economic and public health burden of mosquitoes and agricultural pest insects. Here we describe a new tool for the reliable and targeted genome manipulation of pest insects for research and field release using recombinase mediated cassette exchange (RMCE) mechanisms. We successfully demonstrated the established ΦC31-RMCE method in the yellow fever mosquito, Aedes aegypti, which is the first report of RMCE in mosquitoes. A new variant of this RMCE system, called iRMCE, combines the ΦC31-att integration system and Cre or FLP-mediated excision to remove extraneous sequences introduced as part of the site-specific integration process. Complete iRMCE was achieved in two important insect pests, Aedes aegypti and the diamondback moth, Plutella xylostella, demonstrating the transferability of the system across a wide phylogenetic range of insect pests.     

Biology and demography of Glyphodes pyloalis Walker (Lepidoptera: Pyralidae) on mulberry

Lesser mulberry pyralid, Glyphodes pyloalis Walker, is a monophagous pest of mulberry and has recently been reported in northern Iran. The biology and life table of this pest were studied in controlled conditions (24 ± 1 °C, 75 ± 5% RH and 16:8 LD). Mortality rate, metamorphosis, appearance of adult insects and adult sex ratio were recorded daily. Data were analyzed based on an age-stage, two-sex life table. Developmental rate among individuals and between sexes were also considered. The developmental periods for the egg, first through fifth instar larvae, prepupae and pupae were 4.06 ± 0.03, 2.93 ± 0.03, 2.03 ± 0.02, 2.01 ± 0.01, 2.10 ± 0.03, 4.09 ± 0.03, 2.04 ± 0.02 and 9.7 ± 0.09 days, respectively. The mean total developmental period from egg to adult was 35.40 ± 0.37 days. The maximum adult longevity was 7 and 11 days for males and females, respectively. The pre-oviposition period lasted 2.14 ± 0.04 days. Laboratory observation showed that adults are nocturnal and female lay eggs at night. The intrinsic rate of increase (r_m) and the finite rate of increase (λ) were 0.14 ± 0.005 d^? 1 and 1.15 ± 0.01 d^? 1. The net reproductive rate (R₀), gross reproductive rate (GRR) and mean generation time (T) were 134.67 ± 20.6 female offspring, 294.71 ± 4.07 eggs/female and 34.44 ± 0.2 days, respectively. Life expectancy of freshly laid egg was 32.15 days.     

Mapping the protein interaction network in methicillin-resistant Staphylococcus aureus

Mortality attributable to infection with methicillin-resistant Staphylococcus aureus (MRSA) has now overtaken the death rate for AIDS in the United States, and advances in research are urgently needed to address this challenge. We report the results of the systematic identification of protein-protein interactions for the hospital-acquired strain MRSA-252. Using a high-throughput pull-down strategy combined with quantitative proteomics to distinguish specific from nonspecific interactors, we identified 13,219 interactions involving 608 MRSA proteins. Consecutive analyses revealed that this protein interaction network (PIN) exhibits scale-free organization with the characteristic presence of highly connected hub proteins. When clinical and experimental antimicrobial targets were queried in the network, they were generally found to occupy peripheral positions in the PIN with relatively few interacting partners. In contrast, the hub proteins identified in this MRSA PIN that are essential for network integrity and stability have largely been overlooked as drug targets. Thus, this empirical MRSA-252 PIN provides a rich source for identifying critical proteins essential for network stability, many of which can be considered as prospective antimicrobial drug targets.     

Disruption of tubulin polymerization and cell proliferation by 1-naphthylarsonic acid

Arsenical compounds exhibit a differential toxicity to cancer cells. Microtubules are a primary target of a number of anticancer drugs, such as arsenical compounds. The interaction of 1-NAA (1-naphthylarsonic acid) has been investigated on microtubule polymerization under in vitro and cellular conditions. Microtubules were extracted from sheep brain. Transmission electron microscopy was used to show microtubule structure in the presence of 1-NAA. Computational docking method was applied for the discovery of ligand-binding sites on the microtubular proteins. Proliferation of HeLa cells and HF2 (human foreskin fibroblasts) was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay method following their incubation with 1-NAA. Fluorescence microscopic labelling was done with the help of α-tubulin monoclonal antibody and Tunel kit was used to investigate the apoptotic effects of 1-NAA on the HeLa cells. 1-NAA inhibits the tubulin polymerization by the formation of abnormal polymers having high affinity to the inner cell wall.