Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased — and, under conditions of decreased platelet adhesion, PDI inhibition reduced — fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet–secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury

Engineering and geological features of soils fundamentals buildings and engineering networks of the Dnipro city

The analysis of engineering and geological properties of soils both in the natural state and under the influence of human economic activity is performed in the work. The researches from the point of view of conditions of construction and operation of buildings and constructions of engineering infrastructure of the city of Dnipro are proved. As a result of the analysis of specific geomorphological zones, specific examples of violations of the operation of buildings on subsidence soils, a number of measures are proposed for maintenance and operation of buildings and structures located in areas composed of subsidence soils, on the example of specific areas exposed to past man-made events. An analytical assessment of the ecological catastrophe on the territory of the Topolya 1 railway in 1997 is provided. The paper considers a principled approach to the principles and conditions of operation of buildings and structures on specific subsidence soils of the city of Dnipro.В роботі виконано аналіз інженерно-геологічних властивостей грунтів як в природньому стані, так і під впливом господарської діяльності людини. Доведені дослідження з точки зору умов будівництва і експлуатації будівель та споруд інженерної інфрастуктури міста Дніпро. Внаслідок аналізу конкретних геоморфологічних зон, конкретних прикладів порушень умов експлуатації будівель на просідальних грунтах, пропонується ряд заходів по утриманню і експлуатації будівель і споруд, розташованих на територіях, складених просідальними грунтами, на прикладі конкретних районів, які піддавалися в минулому негативним подіям техногенного характреру. Надається аналітична оцінка екологічної катастрофи на території ж/м "Тополя -1" у 1997 році. В роботі розглядається принциповий підхід до принципів і умов експлуатації будівель і споруд на специфічних просідальних грунтах міста Дніпро