Предварительные результаты бурения параметрической скважины на Новосветловских газовых куполах (Луганская область)

Обсяг робіт, виконаний при бурінні параметричної свердловини на Новосвітлівських газових куполах, і одержані результати дозволили вивчити літолого-стратиграфічний розріз, петрофізичні особливості, газоносні горизонти й визначити наявність вугільних ( у тому числі й зближених) пластів; установити закономірності, які дають можливість обгрунтовано підходити до вибору місць закладання параметричних свердловин, що позитивно відобразиться на економічній складовій «Проекту буріння…» [1].Scope of work executed in drilling wells on parametric Novosvitlivskyh gas domes, and the results obtained allowed to examine lithological and stratigraphic section, petrofizychni features hazonosni horizons and determine the presence of coal (including adjacent) layers, set the patterns that enable the necessity to treat choice for laying parametric wells, which will positively affect the economic component of the «Project drilling…» [1]

The Weibel-Palade Body Localized SNARE (Soluble NSF Attachment Protein Receptor) Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells

Objective Endothelial cells store von Willebrand factor (VWF) in rod-shaped secretory organelles, called Weibel-Palade bodies (WPBs). WPB exocytosis is coordinated by a complex network of Rab GTPases, Rab-effectors and SNARE proteins. We have previously identified STXBP1 as the link between the Rab27A-Slp4-a complex on WPBs and the SNARE proteins syntaxin-2 and -3. In this study we investigate the function of syntaxin-3 in VWF secretion. Approach and Results In human umbilical vein endothelial cells (HUVECs) and in blood outgrowth endothelial cells (BOECs) from healthy controls endogenous syntaxin-3 immunolocalized to WPBs. A detailed analysis of BOECs isolated from a patient with variant microvillus inclusion disease (MVID), carrying a homozygous mutation in STX3 (STX3-/-), showed a loss of syntaxin-3 protein and absence of WPB-associated syntaxin-3 immunoreactivity. Ultrastructural analysis revealed no detectable differences in morphology or prevalence of immature or mature WPBs in control versus STX3-/- BOECs. VWF multimer analysis showed normal patterns in plasma of the MVID patient, and media from STX3-/- BOECs, together indicating WPB formation and maturation are unaffected by absence of syntaxin-3. However, a defect in basal as well as Ca2+ - and cAMP-mediated VWF secretion was found in the STX3-/- BOECs. We also show that syntaxin-3 interacts with the WPB-associated SNARE protein VAMP8. Conclusions Our data reveal syntaxin-3 as a novel WPB-associated SNARE protein that controls WPB exocytosis

STXBP1 promotes Weibel-Palade body exocytosis through its interaction with the Rab27A effector Slp4-a.

Vascular endothelial cells contain unique rod-shaped secretory organelles, called Weibel-Palade bodies (WPBs), which contain the hemostatic protein von Willebrand factor (VWF) and a cocktail of angiogenic and inflammatory mediators. We have shown that the Rab27A effector synaptotagmin-like protein 4-a (Slp4-a) plays a critical role in regulating hormone-evoked WPB exocytosis. Using a nonbiased proteomic screen for targets for Slp4-a, we now identify syntaxin-binding protein 1 (STXBP1) and syntaxin-2 and -3 as endogenous Slp4-a binding partners in endothelial cells. Coimmunoprecipitations showed that STXBP1 interacts with syntaxin-2 and -3, but not with syntaxin-4. Small interfering RNA-mediated silencing of STXBP1 expression impaired histamine- and forskolin-induced VWF secretion. To further substantiate the role of STXBP1, we isolated blood outgrowth endothelial cells (BOECs) from an early infantile epileptic encephalopathy type 4 (EIEE4) patient carrying a de novo mutation in STXBP1. STXBP1-haploinsufficient EIEE4 BOECs contained similar numbers of morphologically normal WPBs compared with control BOECs of healthy donors; however, EIEE4 BOECs displayed significantly impaired histamine- and forskolin-stimulated VWF secretion. Based on these findings, we propose that the Rab27A-Slp4-a complex on WPB promotes exocytosis through an interaction with STXBP1, thereby controlling the release of vaso-active substances in the vasculature

Interaction between MyRIP and the actin cytoskeleton regulates Weibel-Palade body trafficking and exocytosis.

Weibel-Palade body (WPB)-actin interactions are essential for the trafficking and secretion of von Willebrand factor, yet, the molecular basis for this interaction remains poorly defined. Myosin Va (MyoVa) is recruited to WPBs by a Rab27A-MyRIP complex and is thought to be the prime mediator of actin binding, however, direct MyRIP-actin interactions can also occur. To evaluate the specific contribution of MyRIP-actin and MyRIP-MyoVa binding in WPB trafficking and Ca(2+)-driven exocytosis we used EGFP-MyRIP point mutants with disrupted MyoVa and/or actin binding and high-speed live-cell fluorescence microscopy. We now show that the ability of MyRIP to restrict WPB movement depends upon its actin rather than MyoVa binding properties. We also show that although the role of MyRIP in Ca(2+)-driven exocytosis requires both MyoVa and actin binding potential, it is the latter that plays a dominant role. In view of these results and together with the analysis of actin disruption or stabilisation experiments we propose that the role of MyRIP in regulating WPB trafficking and exocytosis is mediated largely through its interaction with actin rather than with MyoVa

Tuning the SNAREs that regulate Weibel-Palade body exocytosis

Endothelial cells form the inner lining of the vessel wall and provide a barrier between circulating blood and the underlying tissue. The endothelium participates in maintenance of vascular homeostasis and facilitates rapid responses to environmental changes such as inflammation or vascular damage. A cocktail of bioactive components participating in these processes are stored in endothelial-specific storage organelles, designated Weibel-Palade bodies (WPBs). The main component of WPBs is von Willebrand factor (VWF). VWF functions in arrest of bleeding by capturing platelets thereby promoting thrombus formation at sites of vascular injury. Furthermore, VWF acts as a carrier for coagulation factor VIII. Several other mediators of hemostasis, inflammation and angiogenesis are co-stored with VWF in WPBs and are secreted into the vascular lumen upon WPB exocytosis. In this thesis we aim to obtain a better understanding of the composition of WPBs and the molecular mechanisms that regulate the release of WPB components into the bloodstream

Global status report on energy efficiency 2008

There is wide agreement that energy efficiency improvement is one of the key strategies to achieve greater sustainability of the energy system. In the past, the contribution of energy efficiency has already been considerable.Without the energy efficiency improvements achieved since the 1970s, current energy use would have been much higher. However, the potential for energy efficiency improvement is much larger than has already been implemented. In the period leading to 2050, it is possible to stabilise worldwide energy use at the current level, while economic growth continues at 2.7 percent per year. However, this will require the ambitious adoption of existing and new energy-efficient technologies. In addition, policies to promote energy efficiency are very important to overcome existing market barriers such as high initial investment costs, split incentives, lack of information and ingrained habits of producers and consumers. In this report, we evaluate the progress in the field of energy efficiency in various sectors such as buildings and appliances, manufacturing industry, transport, agriculture and energy supply in the past years as well as the potential for further energy efficiency improvements for the coming years. This report also addresses what is required to enhance and speed up the rate of energy efficiency improvements to reach its potential levels

Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 1 regulates epinephrine-induced exocytosis of Weibel-Palade bodies

Thrombosis and Hemostasi