Higher education: problems and opportunities

В статье обосновано, что современная молодежь стремится к получению высшего образования, так как профессиональная карьера невозможна без качественного высшего образования, которое может быть получено, как в российских, так и зарубежных университетах.In the article it is justified that the contemporary youth is striving for higher education, because it is impossible to make a professional career without a high-quality education that can be obtained both at Russian and foreign universities

Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice

Background: The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. Methodology/Principal Findings: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ONand OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina

Blockade of VEGFR1 and 2 Suppresses Pathological Angiogenesis and Vascular Leakage in the Eye

VEGFR1 and 2 signaling have both been increasingly shown to mediate complications of ischemic retinopathies, including retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). This study evaluates the effects of blocking VEGFR1 and 2 on pathological angiogenesis and vascular leakage in ischemic retinopathy in a model of ROP and in choroidal neovascularization (CNV) in a model of AMD.H]-mannitol leakage from blood vessels into the retina. Gene expression was measured by real-time quantitative (Q)PCR.VEGFR1 and VEGFR2 expressions were up-regulated during CNV pathogenesis. Both MF1 and DC101 significantly suppressed CNV at 50 mg/kg: DC101 suppressed CNV by 73±5% (p<0.0001) and MF1 by 64±6% (p = 0.0002) in a dosage-dependent manner. The combination of MF1 and DC101 enhanced the inhibitory efficacy and resulted in an accumulation of retinal microglia at the CNV lesion. Similarly, both MF1 and DC101 significantly suppressed retinal NV in OIR at 50 mg/kg: DC101 suppressed retinal NV by 54±8% (p = 0.013) and MF1 by 50±7% (p<0.0002). MF1 was even more effective at inhibiting ischemia-induced BRB breakdown than DC101: the retina/lung leakage ratio for MF1 was reduced by 73±24%, p = 0.001 and for DC101 by 12±4%, p = 0.003. The retina/renal leakage ratio for MF1 was reduced by 52±28%, p = 0.009 and for DC101 by 13±4%, p = 0.001.Our study provides further evidence that both VEGFR1 and 2 mediate pathological angiogenesis and vascular leakage in these models of ocular disease and suggests that antagonist antibodies to these receptor tyrosine kinases (RTKs) are potential therapeutic agents

Bone marrow-derived cells in ocular neovascularization: contribution and mechanisms

Ocular neovascularization often leads to severe vision loss. The role of bone marrow-derived cells (BMCs) in the development of ocular neovascularization, and its significance, is increasingly being recognized. In this review, we discuss their contribution and the potential mechanisms that mediate the effect of BMCs on the progression of ocular neovascularization. The sequence of events by which BMCs participate in ocular neovascularization can be roughly divided into four phases, i.e., mobilization, migration, adhesion and differentiation. This process is delicately regulated and liable to be affected by multiple factors. Cytokines such as vascular endothelial growth factor, granulocyte colony-stimulating factor and erythropoietin are involved in the mobilization of BMCs. Studies have also demonstrated a key role of cytokines such as stromal cell-derived factor-1, tumor necrosis factor-α, as well as vascular endothelial growth factor, in regulating the migration of BMCs. The adhesion of BMCs is mainly regulated by vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and vascular endothelial cadherin. However, the mechanisms regulating the differentiation of BMCs are largely unknown at present. In addition, BMCs secrete cytokines that interact with the microenvironment of ocular neovascularization; their contribution to ocular neovascularization, especially choroidal neovascularization, can be aggravated by several risk factors. An extensive regulatory network is thought to modulate the role of BMCs in the development of ocular neovascularization. A comprehensive understanding of the involved mechanisms will help in the development of novel therapeutic strategies related to BMCs. In this review, we have limited the discussion to the recent progress in this field, especially the research conducted at our laboratory

Extension of the Calibration of an NE-213 Liquid Scintillator Based Pulse Height Response Spectrometer up to 18 MeV Neutron Energy and Leakage Spectrum Measurements on Bismuth at 8 MeV and 18 MeV Neutron Energies

Monoenergetic neutrons were produced at the Van de Graaf accelerator of the EC-JRC-Institute for Reference Materials and Measurements (IRMM, Geel, Belgium). An air-jet cooled D2-gas target (1.2 bar, Ed = 448 keV) was bombarded with Ed =4976 keV deuterons to produce neutrons up to En = 8 MeV energy via the D(d,n)3He reaction. Higher energy neutrons up to En = 18 MeV were produced via the T(d,n)4He reaction by bombarding a TiT target with Ed =1968 keV deuterons. Pulse height spectra were measured at different neutron energies from En = 8 MeV up to En = 18 MeV with the NE-213 liquid scintillator based Pulse Height Response Spectrometer (PHRS) of UD-IEP. The energy calibration of the PHRS system has been extended up to En = 18 MeV. Pulse height spectra induced by gamma photons have been simulated by the GRESP7 code. Neutron induced pulse height spectra have been simulated by the NRESP7 and MCNP-POLIMI codes. Comparison of the results of measurements and simulations enables the improvement of the parameter set of the function used by us to describe the light output dependence of the resolution of the PHRS system at light outputs of L > 2 light units. Also, it has been shown that the derivation method for unfolding neutron spectra from measured pulse height spectra performs well when relative measurements are done up to En = 18 MeV neutron energy. For matrix unfolding purposes, the NRESP7 code has to be preferred to calculate the pulse height response matrix of the PHRS system. Leakage spectra of neutrons behind bismuth slabs of different thicknesses have been measured with the PHRS system by using monoenergetic neutrons. The maximum slab thickness was d = 14 cm. Simulations of the measurements have been carried out with the MCNP-4c code. The necessary nuclear cross sections were taken from the from the ENDF/B-VII and JEFF-3.1 data libraries. For both libraries, the agreement of measured and simulated neutron spectra is good for the 5 MeV = En smaller than or equal to 18 MeV neutron energy region. However, for both libraries, the observed differences between measured and simulated neutron spectra are beyond statistical uncertainty for the En < 5 MeV region. Further experimental check of cross section data of the two libraries for bismuth is recommended for the En < 5 MeV region.JRC.D.5-Nuclear physic

Overexpression of FasL in retinal pigment epithelial cells reduces choroidal neovascularization

Choroidal neovascularization (CNV) is responsible for the severe visual loss in age-related macular degeneration. CNV formation is considered to be due to an imbalance between pro- and antiangiogenic factors that lead to neovascular growth from the choriocapillaris into the subretinal space. To define whether FasL overexpression in retinal pigment epithelial cells (RPE) can inhibit choroidal neovascularization through Fas-FasL-mediated apoptosis, we examined the role of this pathway in a mouse model of laser-induced choroidal neovascularization. FasL was expressed in the retinal pigment epithelium of transgenic mice. Polymerase chain reaction (PCR), immunoblot, and immunohistochemistry confirmed that the transgene FasL was specifically expressed in RPE. The established laser model was used to induce choroidal neovascularization (CNV) in wild-type (WT) and transgenic mice. CNV formation was compared with respect to fluorescein angiographic leakage (at days 0 and 14 after laser injury) and histological appearance. The lesions were assessed on RPE-choroidal flatmounts after CD31-labeling and with confocal microscopy after perfusion with rhodamine-labeled concanavalin A (Con A). Apoptosis was quantified by TUNEL positivity and caspase activation. FasL mRNA and protein were highly expressed in the RPE of the transgenic mice before and after laser photocoagulation. In contrast, FasL was only weakly expressed in the RPE layer of WT C57BL/6J mice. While ruptures of Bruch’s membrane and CNV formation were observed histologically two weeks after laser photocoagulation in transgenic as well as control eyes, the shape and size of CNV lesions were reduced in the transgenic mice. The area of leakage was decreased by 70% in FasL transgenic mice compared with WT mice (P&lt;0.005). The number of TUNEL-positive cells was greater in FasL-overexpressing mice and correlated with the expression of activated caspases. Th expression of other antiangiogenic factors such as PEDF remained unchanged. The specific overexpression of FasL in RPE layer reduced CNV formation in our laser model. Our results strongly point to the FasL-Fas pathway as a potential therapeutic target in controlling pathological choroidal neovascularization.--Semkova, I., Fauser, S., Lappas, A., Smyth, N., Kociok, N., Kirchhof, B., Paulsson, M., Poulaki, V., Joussen, A. M. Overexpression of FASL in retinal pigment epithelial cells reduces choroidal neovascularization