L-and T-type Ca^(2+)channels dichotomously contribute to retinal ganglion cell injury in experimental glaucoma

Retinal ganglion cell apoptotic death is the main pathological characteristic of glaucoma,which is the leading cause of irreversible blindness.Disruption of Ca^(2+)homeostasis plays an important role in glaucoma.Voltage-gated Ca^(2+)channel blockers have been shown to improve vision in patients with glaucoma.However,whether and how voltage-gated Ca^(2+)channels are involved in retinal ganglion cell apoptotic death are largely unknown.In this study,we found that total Ca^(2+)current densities in retinal ganglion cells were reduced in a rat model of chronic ocular hypertension experimental glaucoma,as determined by whole-cell patch-clamp electrophysiological recordings.Further analysis showed that L-type Ca^(2+)currents were downregulated while T-type Ca^(2+)currents were upregulated at the later stage of glaucoma.Western blot assay and immunofluorescence experiments confirmed that expression of the Ca_(V)1.2 subunit of L-type Ca^(2+)channels was reduced and expression of the Ca_(V)3.3 subunit of T-type Ca^(2+)channels was increased in retinas of the chronic ocular hypertension model.Soluble tumor necrosis factor-α,an important inflammatory factor,inhibited the L-type Ca^(2+)current of isolated retinal ganglion cells from control rats and enhanced the T-type Ca^(2+)current.These changes were blocked by the tumor necrosis factor-αinhibitor XPro1595,indicating that both types of Ca^(2+)currents may be mediated by soluble tumor necrosis factor-α.The intracellular mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and nuclear factor kappa-B signaling pathway mediate the effects of tumor necrosis factor-α.TUNEL assays revealed that mibefradil,a T-type calcium channel blocker,reduced the number of apoptotic retinal ganglion cells in the rat model of chronic ocular hypertension.These results suggest that T-type Ca^(2+)channels are involved in disrupted Ca^(2+)homeostasis and apoptosis of retinal ganglion cells in glaucoma,and application of T-type Ca^(2+)channel blockers,especially a specific CaV3.3 blocker,may be a potential strategy for the treatment of glaucoma.

国家完全统一进程中的渐进治理(笔谈)

台湾问题的知识体系和话语体系,已经在人们熟悉的一个中国原则、国家统一等话语基础上,发展出两岸关系和平发展、两岸融合发展、涉台公共政策等新元素,这是台湾问题内外环境发展变化的结果,也显示台湾研究正在朝向深层次发展。从国家治理体系和治理能力现代化层面思考台湾问题,让我们有可能以更宽广的视野和更新的角度观察和思考两岸完全统一问题。治理理论的引进,让我们发现除了公权力部门这一传统的两岸关系行动者之外,还存在大量的民间社会力量。即使是公权力部门内部,也有众多平行的部门关系和垂直的府际关系,笼统的“公权力部门”并不足以反映机构之间的相对自主性;而民间社会组织的创造力正在全方位改变着两岸关系的环境体系。

Discovery of unique African Helicobacter pylori CagAmultimerization motif in the Dominican Republic

BACKGROUND Helicobacter pylori(H.pylori)colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer.However,although the prevalence of H.pylori is high in Africa,the incidence of gastric cancer is low,and this phenomenon is called to be African enigma.The CagA protein produced by H.pylori is the most studied virulence factor.The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala(EPIYA)patterns and CagAmultimerization(CM)motifs.AIM To better understand the EPIYA patterns and CM motifs of the cagA gene.METHODS Gastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic,from which 120 H.pylori strains were cultured.After the bacterial DNA extraction,the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing.The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing(MLST).Peptic ulcer disease and gastric cancer were identified via endoscopy,and gastric cancer was confirmed by histopathology.Histological scores of the gastric mucosa were evaluated using the updated Sydney system.RESULTS All CagA-positive strains carried the Western-type CagA according to the identified EPIYA patterns.Twenty-seven kinds of CM motifs were observed.Although the typical Western CM motif(FPLKRHDKVDDLSKVG)was observed most frequently,the typical East Asian CM motif(FPLRRSAAVNDLSKVG)was not observed.However,“FPLRRSAKVEDLSKVG”,similar to the typical East Asian CM motif,was found in 21 strains.Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis(P=0.034),we termed it Africa1-CM(Af1-CM).A few hpEurope strains carried the Af1-CM motif,but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif(P=0.030).In 30 cagA-positive strains,the"GKDKGPE"motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment,and there was a significant association between strains with the hpAfrica1 population and those containing the“GKDKGPE”motif(P=0.018).In contrast,there was no significant association between the CM motif patterns and histological scores and clinical outcomes.CONCLUSION We found the unique African CM motif in Western-type CagA and termed it Africa1-CM.The less toxicity of this motif could be one reason to explain the African enigma.

On First Order Optimality Conditions for Vector Optimization

We develop first order optimality conditions for constrained vector optimization. The partial orders for the objective and the constraints are induced by closed and convex cones with nonempty interior. After presenting some well known existence results for these problems, based on a scalarization approach, we establish necessity of the optimality conditions under a Slater-like constraint qualification, and then sufficiency for the K-convex case. We present two alternative sets of optimality conditions, with the same properties in connection with necessity and sufficiency, but which are different with respect to the dimension of the spaces to which the dual multipliers belong. We introduce a duality scheme, with a point-to-set dual objective, for which strong duality holds. Some examples and open problems for future research are also presented.

On a Class of Solutions to the Generalized Derivative Schrodinger Equations

In this work we shall consider the initial value problem associated to the generalized derivative Schr?dinger(gDNLS) equations ■ and ■ Following the argument introduced by Cazenave and Naumkin we shall establish the local well-posedness for a class of small data in an appropriate weighted Sobolev space. The other main tools in the proof include the homogeneous and inhomogeneous versions of the Kato smoothing effect for the linear Schr?dinger equation established by Kenig–Ponce–Vega.

极小曲面-变分理论及其应用

极小曲面在微分几何中是很自然的研究对象，且自Lagrange（拉格朗日）开创性的工作以来，其研究已经持续250多年了．这一领域以拥有大量漂亮的、或许可以讲拥有杰出的结果为其特征，极小曲面（或称极小子流形）在其他领域中也有引人注目的应用，