TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom, activates platelet via GPIb

TMVA is a C-type lectin-like protein with potent platelet activating activity from Trimeresurus mucrosquamatus venom. In the absence of von Willebrand factor (vWF), TMVA dose-dependently induced aggregation of washed platelets. Anti-GP Ib monoclonal antib

蓝裸甲藻有性生殖的初步观察

<正> 早在1879年,Joseph就描述了Peridinium stygium的配子融合现象。之后的近八十年中,对甲藻生活史中是否存在有性生殖一直存在着争论。直至Von Stosch(1964)报道了Ceratium horridium和C.cornutum有性生殖核配的详细过程后,甲藻的有性生殖才得到公认。迄今,至少已在15属30种甲藻的生活史中观察到有性阶段。 Andersoa等人经大量的研究,证明:Gonyaulax tamarensis的周期性赤潮起源于海底沉积物中的休眠合子。在Gonyaula

El Ser como mediación. Ontología, estética y analogía en la interpretación del ‘esse’ tomasiano de H. U. von Balthasar

El presente artículo expone los fundamentos de la interpretación que del esse tomasiano lleva a cabo Hans Urs von Balthasar. En ella ofrece von Balthasar, a partir de una interpretación en la línea de Siewerth, y como tal novedosa para la historia de la crítica, las directrices fundamentales de su propio pensamiento filosóficoteológico, cuyo eje lo constituye la diferencia entre esse y Dios como modelo para una hermenéutica no monista de la realidad. Con todo, la propuesta no está exenta de algunas dificultades y arbitrariedades que, desde una perspectiva crítica y aconfesional (por la que aquí se opta), conviene ineludiblemente subrayar.

Zur kognitiven Konstruktion von (Un-)Gerechtigkeit militärischer Gewalt: Die moralische Beurteilung des Kosovo-Kriegs

With reference to the Kosovo war, we examined how the (un-)justness of military intervention is cognitively constructed. Four types of reinterpretation were hypothesized to relate to positive evaluation of the intervention: minimisation of negative consequences of NATO's intervention, denial of responsibility of the Western countries for the war, blame of Yugoslavia, and justification of the intervention through positive motives. As determinants of evaluation of the war, belief in a just world, militarism-pacifism, authoritarianism, and diffuse political support were taken into account. Hypotheses were tested with 165 university students using structural equation modelling. Consistent with our assumptions, the four types of reinterpretation related strongly to positive evaluation of the intervention, showing their relevance with regard to military intervention. Further, the assessed political attitudes influenced evaluation of the war while, contrary to predictions, belief in a just world did not. The causal status of the reinterpretations and the interplay of belief in a just world and political attitudes are discussed.

Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline.

Abstract A classic physiologic response to hypoxia in humans is the up-regulation of the ERYTHROPOIETIN (EPO) gene, which is the central regulator of red blood cell mass. The EPO gene, in turn, is activated by hypoxia inducible factor (HIF). HIF is a transcription factor consisting of an alpha subunit (HIF-alpha) and a beta subunit (HIF-beta). Under normoxic conditions, prolyl hydroxylase domain protein (PHD, also known as HIF prolyl hydroxylase and egg laying-defective nine protein) site specifically hydroxylates HIF-alpha in a conserved LXXLAP motif (where underlining indicates the hydroxylacceptor proline). This provides a recognition motif for the von Hippel Lindau protein, a component of an E3 ubiquitin ligase complex that targets hydroxylated HIF-alpha for degradation. Under hypoxic conditions, this inherently oxygen-dependent modification is arrested, thereby stabilizing HIF-alpha and allowing it to activate the EPO gene. We previously identified and characterized an erythrocytosis-associated HIF2A mutation, G537W. More recently, we reported two additional erythrocytosis-associated HIF2A mutations, G537R and M535V. Here, we describe the functional characterization of these two mutants as well as a third novel erythrocytosis-associated mutation, P534L. These mutations affect residues C-terminal to the LXXLAP motif. We find that all result in impaired degradation and thus aberrant stabilization of HIF-2alpha. However, each exhibits a distinct profile with respect to their effects on PHD2 binding and von Hippel Lindau interaction. These findings reinforce the importance of HIF-2alpha in human EPO regulation, demonstrate heterogeneity of functional defects arising from these mutations, and point to a critical role for residues C-terminal to the LXXLAP motif in HIF-alpha.

Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation

The hypoxia-inducible factors (HIFs; isoforms HIF-1 alpha, HIF-2 alpha, HIF-3 alpha) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2 alpha gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2 alpha gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2 alpha gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2 alpha gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1 alpha is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.-Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation. FASEB J. 25, 2001-2011 (2011). www.fasebj.org