PROGNOSTIC FACTORS OF OUTCOMES OF TREATMENT OF ACUTE NONSPECIFIC EMPIEMA PLEURAE

The purpose of the given work is specification adverse prognostical criteria of outcomes of treatment of acute nonspecific empiema pleurae. Work is based on the results of complex treatment of 123 patients with empiema pleurae of not traumatic character. The acute abscess and a lung gangrene (37,9 %) was a principal cause of development of empiema. It is established that the most authentic factors of failures of treatment of empiema were overdue diagnostics acute empiema pleurae; defects and errors in treatment; insufficient preoperative preparation of the patient; an insufficient skill level of the surgeon; late reference for medical aid. Preventive maintenance of the specified defects of rendering of medical aid for the patient with acute empiema pleurae will allow to improve results of treatment of patients with the given pathology

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis on binding to its receptors, death receptor 4 and 5 (DR4, DR5). TRAIL can also activate c-Jun N-terminal kinase (JNK) through the adaptor molecules, TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP). The role of JNK in TRAIL-induced tumour cell apoptosis is unclear. In this study, we demonstrate that JNK is activated by TRAIL in colon cancer cells. Inhibition of JNK with L-JNKI reduced rhTRAIL-induced cell death but enhanced cell death induced by selective activation of DR4 or DR5. This difference was unrelated to receptor internalisation or differential activation of c-Jun, but activation of different JNK isoforms. Our data demonstrate that JNK1, but not JNK2 is activated by rhTRAIL in the examined colon cancer cell lines. Although rhTRAIL activated both the long and short isoforms of JNK1, selective activation of DR4 or DR5 led to predominant activation of the short JNK1 isoforms (JNK1α1 and/or JNK1β1). Knockdown of JNK1α1 by shRNA enhanced apoptosis induced by TRAIL, agonistic DR4 or DR5 antibodies. On the other hand, knockdown of the long JNK1 isoforms (JNK1α2 and JNK1β2) had the opposite effect; it reduced TRAIL-induced cell death. These data indicate that the short JNK1 isoforms transmit an antiapoptotic signal, whereas the long isoforms (JNK1α2 or JNK1β2) act in a proapoptotic manner

Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders

Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2

The inhibitors of apoptosis (IAP) proteins cIAP1 and cIAP2 have recently emerged as key ubiquitin-E3 ligases regulating innate immunity and cell survival. Much of our knowledge of these IAPs stems from studies using pharmacological inhibitors of IAPs, dubbed Smac mimetics (SMs). Although SMs stimulate auto-ubiquitylation and degradation of cIAPs, little is known about the molecular determinants through which SMs activate the E3 activities of cIAPs. In this study, we find that SM-induced rapid degradation of cIAPs requires binding to tumour necrosis factor (TNF) receptor-associated factor 2 (TRAF2). Moreover, our data reveal an unexpected difference between cIAP1 and cIAP2. Although SM-induced degradation of cIAP1 does not require cIAP2, degradation of cIAP2 critically depends on the presence of cIAP1. In addition, degradation of cIAP2 also requires the ability of the cIAP2 RING finger to dimerise and to bind to E2s. This has important implications because SM-mediated degradation of cIAP1 causes non-canonical activation of NF-κB, which results in the induction of cIAP2 gene expression. In the absence of cIAP1, de novo synthesised cIAP2 is resistant to the SM and suppresses TNFα killing. Furthermore, the cIAP2-MALT1 oncogene, which lacks cIAP2's RING, is resistant to SM treatment. The identification of mechanisms through which cancer cells resist SM treatment will help to improve combination therapies aimed at enhancing treatment response

Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity

Thermodynamic properties of myo-inositol

© 2017 Elsevier Ltd In the present work, the temperature dependence of heat capacity of vitamin B8 (myo-inositol) has been measured for the first time over the range from 8 K to 340 K by precision adiabatic vacuum calorimetry. Based on the experimental data, the thermodynamic functions of the vitamin B8, namely, the heat capacity, enthalpy H°(T)–H°(0), entropy S°(T)–S°(0) and Gibbs function G°(T)–H°(0) have been determined for the range from T → 0 K to 340 K. The value of the fractal dimension D in the function of multifractal generalization of Debye's theory of the heat capacity of solids was estimated and the character of heterodynamics of structure was detected. The enthalpy of combustion (−2747.0 ± 2.1) kJ·mol−1 of the vitamin B8 was measured for the first time using high-precision combustion calorimeter. The standard molar enthalpy of formation in the crystalline state (−1329.3 ± 2.3) kJ·mol−1 of B8 at 298.15 K was derived from the combustion experiments. Using combination of the adiabatic and combustion calorimetry results the thermodynamic functions of formation of the myo-inositol at T = 298.15 K and p = 0.1 MPa have been calculated. The low-temperature X-ray diffraction was used for the determination of coefficients of thermal expansion

Volumes of polytopes in spaces of constant curvature

We overview the volume calculations for polyhedra in Euclidean, spherical and hyperbolic spaces. We prove the Sforza formula for the volume of an arbitrary tetrahedron in $H^3$ and $S^3$. We also present some results, which provide a solution for Seidel problem on the volume of non-Euclidean tetrahedron. Finally, we consider a convex hyperbolic quadrilateral inscribed in a circle, horocycle or one branch of equidistant curve. This is a natural hyperbolic analog of the cyclic quadrilateral in the Euclidean plane. We find a few versions of the Brahmagupta formula for the area of such quadrilateral. We also present a formula for the area of a hyperbolic trapezoid.Comment: 22 pages, 9 figures, 58 reference

Bremsstrahlung Suppression due to the LPM and Dielectric Effects in a Variety of Materials

The cross section for bremsstrahlung from highly relativistic particles is suppressed due to interference caused by multiple scattering in dense media, and due to photon interactions with the electrons in all materials. We present here a detailed study of bremsstrahlung production of 200 keV to 500 MeV photons from 8 and 25 GeV electrons traversing a variety of target materials. For most targets, we observe the expected suppressions to a good accuracy. We observe that finite thickness effects are important for thin targets.Comment: 52 pages, 13 figures (incorporated in the revtex LaTeX file

SMG1 and NIK regulate apoptosis induced by Smac mimetic compounds

Smac mimetic compounds (SMCs) are experimental small molecules that induce tumour necrosis factor alpha (TNFα)-dependent cancer cell death by targeting the inhibitor of apoptosis proteins. However, many cancer cell lines are resistant to SMC-mediated apoptosis despite the presence of TNFα. To add insight into the mechanism of SMC-resistance, we used functional siRNA-based kinomic and focused chemical screens and identified suppressor of morphogenesis in genitalia-1 (SMG1) and NF-κB-inducing kinase (NIK) as novel protective factors. Both SMG1 and NIK prevent SMC-mediated apoptosis likely by maintaining FLICE inhibitory protein (c-FLIP) levels to suppress caspase-8 activation. In SMC-resistant cells, the accumulation of NIK upon SMC treatment enhanced the activity of both the classical and alternative nuclear factor-κB pathways, and increased c-FLIP mRNA levels. In parallel, persistent SMG1 expression in SMC-resistant cells repressed SMC-mediated TNFα-induced JNK activation and c-FLIP levels were sustained. Importantly, SMC-resistance is overcome by depleting NIK and SMG1, which appear to facilitate the downregulation of c-FLIP in response to SMC and TNFα treatment, leading to caspase-8-dependent apoptosis. Collectively, these data show that SMG1 and NIK function as critical repressors of SMC-mediated apoptosis by potentially converging on the regulation of c-FLIP metabolism

Comprehensive study of the thermodynamic properties for 2-methyl-3-buten-2-ol

© 2015 Elsevier Ltd. All rights reserved. The heat capacity of 2-methyl-3-buten-2-ol over the interval T = (5 to 370) K was measured in an adiabatic calorimeter. The standard entropy and heat capacity of the liquid phase at a reference temperature 298.15 K were found to be Som = (232.6 ± 1.0) J·K-1·mol-1 and Cs,m = (237.4 ± 0.9) J·K-1·mol-1. The triple-point temperature Tfus = (245.03 ± 0.03) K and the corresponding enthalpy of fusion ΔcrlHom = (5.199 ± 0.012) kJ·mol-1 were also determined. The enthalpy of vaporisation was determined with a Calvet-type calorimeter to be ΔlgHmo(305.1K) = (46.9 ± 1.6) kJ·mol-1. The vapour pressure over the temperature interval (280 to 328) K was measured with a static technique. The standard entropy of vaporisation at T = 298.15 K was found to be ΔlgSom = (132.7 ± 0.2) J·K-1·mol-1. The standard enthalpy of combustion for liquid 2-methyl-3-buten-2-ol ΔcHmo(l, 298.15 K) = -(3145.1 ± 2.7) kJ·mol-1 was measured with two static-bomb isoperibol combustion calorimeters. From the experimental data, the standard enthalpies of formation for liquid and gaseous 2-methyl-3-buten-2-ol were found to be ΔfHom(l, 298.15 K) = -(251.6 ± 2.8) kJ·mol-1 and ΔfHom (g, 298.15 K) = -(203.3 ± 2.8) kJ·mol-1, respectively. The latter value was confirmed by high-level quantum chemical calculations. Molecular association in the gas phase and its effect on thermodynamic properties of the compound were discussed