Műemlékek, polgárháború és helyi közösségek : A Duhok régió (iraki Kurdisztán) régészeti öröksége – 3. rész

Az iraki kurdisztáni Duhok régió régészeti örökségéről szóló cikksorozatunk harmadik és utolsó része a kulturális örökséget, annak a helyi társadalom életében betöltött szerepét, és a Szaddám-rezsim által okozott pusztítást vizsgálja. Szaddám uralmának évtizedei kitörölhetetlen nyomot hagytak Észak-Irak társadalmi és kulturális térképén, különösen a kurdisztáni régióban. A rezsimnek a helyi lakosság ellenében, néha a modernizáció jegyében, néha büntető katonai intézkedésként foganatosított kollektivizációs kísérletei átrajzolták a régió településmintázatát, megváltoztatták a hagyományos gazdasági és társadalmi struktúrákat, és tönkretették az épített örökséget

Műemlékek, polgárháború és helyi közösségek. A Duhok régió (iraki Kurdisztán) régészeti öröksége – 2. rész

Ez a cikksorozat az iraki Kurdisztánban található Duhok régió régészeti örökségét mutatja be, és a területen végzett csaknem két évtizedes kutatás eredményein alapul. Bár az elsődleges kutatási témám a jezidi vallás és népcsoport, szintén érdekes volt számomra az a szélesebb kulturális közeg, ahol a jezidik élnek. Így a terület régészeti emlékei, az ezekhez való viszonyulás, és ezek helye a kurdisztáni régió lakosainak kultúráról alkotott elképzeléseiben és történeti identitás-keresésében – legyenek akár jezidik, muszlimok vagy keresztények – felkeltette az érdeklődésemet. A munka jelen, második részében négy kevéssé ismert, a Duhok kormányzóság területén található lelőhelyet és a helyiek ezekhez való viszonyát mutatjuk be

Interactions between Electron and Proton Currents in Excised Patches from Human Eosinophils

The NADPH–oxidase is a plasma membrane enzyme complex that enables phagocytes to generate superoxide in order to kill invading pathogens, a critical step in the host defense against infections. The oxidase transfers electrons from cytosolic NADPH to extracellular oxygen, a process that requires concomitant H+ extrusion through depolarization-activated H+ channels. Whether H+ fluxes are mediated by the oxidase itself is controversial, but there is a general agreement that the oxidase and H+ channel are intimately connected. Oxidase activation evokes profound changes in whole-cell H+ current (IH), causing an approximately −40-mV shift in the activation threshold that leads to the appearance of inward IH. To further explore the relationship between the oxidase and proton channel, we performed voltage-clamp experiments on inside-out patches from both resting and phorbol-12-myristate-13-acetate (PMA)-activated human eosinophils. Proton currents from resting cells displayed slow voltage-dependent activation, long-term stability, and were blocked by micromolar internal [Zn2+]. IH from PMA-treated cells activated faster and at lower voltages, enabling sustained H+ influx, but ran down within minutes, regaining the current properties of nonactivated cells. Bath application of NADPH to patches excised from PMA-treated cells evoked electron currents (Ie), which also ran down within minutes and were blocked by diphenylene iodonium (DPI). Run-down of both IH and Ie was delayed, and sometimes prevented, by cytosolic ATP and GTP-γ-S. A good correlation was observed between the amplitude of Ie and both inward and outward IH when a stable driving force for e− was imposed. Combined application of NADPH and DPI reduced the inward IH amplitude, even in the absence of concomitant oxidase activity. The strict correlation between Ie and IH amplitudes and the sensitivity of IH to oxidase-specific agents suggest that the proton channel is either part of the oxidase complex or linked by a membrane-limited mediator

Pressure-dependent performance of CEN-specified Condensation Particle Counters

One of the most important parameters to quantify an aerosol is the particle number concentration. Condensation Particle Counters (CPCs) are commonly used to measure the aerosol number concentration in the nanometer range. To compare the data from different measurement stations and campaigns it is important to harmonize the instrument specifications, which is why the Technical Specification CEN/TS 16976:2016 was introduced for CPCs. There, the parameters of the CEN-CPC are specified for standard pressure and temperature. However, CEN-CPCs are used in various surroundings, on high mountains or on airplanes, where they are exposed to low-pressure conditions. Here, we present the pressure-dependent performance (including the concentration linearity and counting efficiency) of two different models of CEN-CPCs, the Grimm 5410 CEN and the TSI 3772-CEN. We found that their performance at 1000 hPa and 750 hPa was in accordance with the CEN-technical-specifications. Below 500 hPa, the performance decreased for both CPC-models, but the decrease was different for the two models. To gain insight into the performance of the two CPC-models, we performed a simulation study. This study included simulations of the saturation profiles and calculations of internal particle losses within the CPCs. The simulations reproduced the overall performance decrease with decreasing pressure and reveal that the internal structure of the CPC has a significant influence on the performance. We anticipate our publication to provide a deeper understanding of the counting efficiency of CPCs and their pressure dependence. Our findings might be a starting point for new standards that include the pressure-dependent performance or they could help for designing new CPCs.</p

Extramitochondrial OPA1 and adrenocortical function

We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial 27 Ca2+ signaling and aldosterone production in H295R adrenocortical cells. Since extramitochondrial OPA1 28 (emOPA1) was reported to facilitate cAMP-induced lipolysis, we hypothesized that emOPA1, via the 29 enhanced hydrolysis of cholesterol esters, augments aldosterone production in H295R cells. A few 30 OPA1 immunopositive spots were detected in �40% of the cells. In cell fractionation studies OPA1/COX 31 IV (mitochondrial marker) ratio in the post-mitochondrial fractions was an order of magnitude higher 32 than that in the mitochondrial fraction. The ratio of long to short OPA1 isoforms was lower in post-mito- 33 chondrial than in mitochondrial fractions. Knockdown of OPA1 failed to reduce db-cAMP-induced phos- 34 phorylation of hormone-sensitive lipase (HSL), Ca2+ signaling and aldosterone secretion. In conclusion, 35 OPA1 could be detected in the post-mitochondrial fractions, nevertheless, OPA1 did not interfere with 36 the cAMP – PKA – HSL mediated activation of aldosterone secretio

Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion

Glomerulosa cells secrete aldosterone in response to agonists coupled to Ca2+ increases such as angiotensin II and corticotrophin, coupled to a cAMP dependent pathway. A recently recognized interaction between Ca2+ and cAMP is the Ca2+-induced cAMP formation in the mitochondrial matrix. Here we describe that soluble adenylyl cyclase (sAC) is expressed in H295R adrenocortical cells. Mitochondrial cAMP formation, monitored with a mitochondria-targeted fluorescent sensor (4mtH30), is enhanced by HCO3 - and the Ca2+ mobilizing agonist angiotensin II. The effect of angiotensin II is inhibited by 2-OHE, an inhibitor of sAC, and by RNA interference of sAC, but enhanced by an inhibitor of phosphodiesterase PDE2A. Heterologous expression of the Ca2+ binding protein S100G within the mitochondrial matrix attenuates angiotensin II-induced mitochondrial cAMP formation. Inhibition and knockdown of sAC significantly reduce angiotensin II-induced aldosterone production. These data provide the first evidence for a cell-specific functional role of mitochondrial cAMP. © 2015 Elsevier Ireland Ltd

Decavanadate displaces inositol 1,4,5-trisphosphate (IP3) from its receptor and inhibits IP3 induced Ca2+ release in permeabilized pancreatic acinar cells

Inositol 1,4,5-trisphosphate (IP3) induced Ca2+ release in digitonin permeabilized rat pancreatic acinar cells is specifically inhibited by decavanadate. The Ca2+ release induced with 0.18 μM IP3 is half maximally inhibited with approximately 5 μM decavanadate. Complete inhibition is achieved with around 20 μM decavanadate. Removal of decavanadate from the permeabilized cells fully restores sensitivity towards IP3, indicating the reversibility of the inhibition. Oligovanadate, which inhibits ATP dependent Ca2+ uptake into intracellular stores, does not influence IP3 induced Ca2+ release. In order to reveal the mechanism underlying the effects of the different vanadate species, binding of IP3 to the same cellular preparations was investigated. We found that binding of IP3 to a high affinity receptor site (Kd approx. 1.2 nM) could be abolished by decavanadate but not by oligovanadate. With 0.5 μM decavanadate, IP3 binding was half maximally inhibited. A similar potency of decavanadate was also found with adrenal cortex microsomes which bind IP3 with the same affinity (Kd approx. 1.4 nM) as permeabilized pancreatic acinar cells. Labelled IP3 was displaced from these subcellular membranes with similar kinetics by unlabelled IP3 and decavanadate. The data suggest that the inhibitory action of decavanadate on IP3 induced Ca2+ release is a consequence of its effect on binding of IP3 to its receptor. EGTA, ethylene-glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid; EDTA, ethylenediaminetetraacetic acid; PEG, polyethylene glycol; IP3, inositol 1,4,5-trisphosphate; MOPS, morpholinopropane sulfonic acid; HEPES, N-(2-hydroxyethyl)-piperazine-N′-2-ethanesulfonic acid; Tris, tris(hydroxymethyl)-aminomethan

Signaling interactions in the adrenal cortex

The major physiological stimuli of aldosterone secretion are angiotensin II (AII) and extracellular K+ whereas cortisol production is primarily regulated by corticotrophin (ACTH) in fasciculata cells. AII triggers Ca2+ release from internal stores that is followed by store-operated and voltage-dependent Ca2+ entry whereas K+-evoked depolarisation activates voltage-dependent Ca2+ channels. ACTH acts primarily through the formation of cAMP and subsequent protein phosphorylation by protein kinase A. Both Ca2+ and cAMP facilitate the transfer of cholesterol to mitochondrial inner membrane. The cytosolic Ca2+ signal is transferred into the mitochondrial matrix and enhances pyridine nucleotide reduction. Increased formation of NADH results in increased ATP production whereas that of NADPH supports steroid production. In reality, the control of adrenocortical function is a lot more sophisticated with second messengers crosstalking and mutually modifying each other’s pathways. Cytosolic Ca2+ and cGMP are both capable of modifying cAMP metabolism whilst cAMP may enhance Ca2+ release and voltage-activated Ca2+ channel activity. Besides, mitochondrial Ca2+ signal brings about cAMP formation within the organelle and this further enhances aldosterone production. Maintained aldosterone and cortisol secretion are optimized by the concurrent actions of Ca2+ and cAMP, as exemplified by the apparent synergism of Ca2+ influx (inducing cAMP formation) and Ca2+ release during response to AII. Thus, cross-actions of parallel signal transducing pathways are not mere intracellular curiosities but rather substantial phenomena which fine-tune the biological response. Our review focuses on these functionally relevant interactions between the Ca2+ and the cyclic nucleotide signal transducing pathways hitherto described in the adrenal cortex