Rövid áttekintés a hazai for- és nonprofit szervezetfejlesztés gyakorlati, módszertani helyzetéről és problémáiról = An overview of the practice and methodology related position and problems of the for- and nonprofit organization development in Hungary

A hazai civil-nonprofit szektor a forprofit szektorral egy időben született újjá a rendszerváltást követően. Már akkoriban is világosan látták a szakemberek, ahhoz, hogy fennmaradjanak, hogy megtartsák további fejlődőképességüket, meg kell tanulniuk kezelni a változást, együtt kell tudni vele élni. A kilencvenes évek végére jutnak el a szervezetek abba a fejlődési szakaszba, hogy tudatosan elkezdenek szervezetfejlesztési kérdésekkel foglalkozni, szervezetfejlesztési tanácsadókkal kooperálni. Általánosan elmondható, hogy szükséges a célok és missziók újra definiálása és megtalálása mindkét oldalon. Az elmúlt évek viszontagságai mind a két területen felerősítették a rugalmas alkalmazkodás képességének igényét mind szervezeti, mind emberi oldalról. Minden szervezet szeretne jól gazdálkodni az erőforrásokkal, hatékonyan működni. Nonprofit területen továbbra is kérdés a forrásteremtés és a megfelelő szervezettségű működési szint megtalálása. Számos olyan módszertan és eszköz áll rendelkezésre, mint például a coaching szemlélete és módszertana, ami egy gyakorlatias megoldás a jelen kor kihívásaira. Az elmúlt években megnőtt az igény, hogy maguk a szervezetfejlesztők is hozzájárulnak a civil-nonprofit szektor fejlesztéséhez, ráadásul a fent említett módszertant pedig egyre többen űzik eredményesen, akikben megfogalmazódik az igény a tudásátadásra és visszaadásra. | The Hungarian nonprofit and forprofit sectors were reconstructed simultaneously after the regime change. Even then, professionals confirmed that in order to survive and to be able to further develop, they had to learn to manage change and to live with it. By the end of the 1990s, organisations had reached the stage of development where they consciously began to address issues in organisational development and to cooperate with consultants in this field. Generally speaking, it is necessary to redefine and reinvent goals and missions on both sides. The vicissitudes of recent years have reinforced the need for flexibility in both areas: both the organisational and the human side. Organisations want to manage resources well and operate efficiently. For the notfor-profit sector, generating resources and finding the right level of organisation remain the main challenges. The approach and the methodology of coaching seems to be a practical solution to the challenges of today. In recent years, there has been a growing demand for organisational development practitioners themselves to contribute to the development of the nonprofit sector, and the abovementioned methodologies are being used successfully by an increasing number of people who have a need to transfer and contribute their knowledge

Molekuláris chaperonok és a citoszkeleton kölcsönhatásai = Interactions of molecular chaperones and the cytoskeleton

Munkánk során azonosítottuk a citoplazma leggyakoribb stresszfehérjéje, a Hsp90 második, C-terminális nukleotid kötőhelyét, valamint e fehérje taxol-kötőhelyét, amely új Hsp90 támadáspontú gyógyszerek tervezésére ad lehetőséget. Bebizonyítottuk, hogy a Hsp90 inhibitorok hatásmódjában a megtámadott sejtek erőteljesebb lízise is részt vesz. A chaperonok rendezetlen régióin alapuló új elméletet dolgoztunk ki működésük megértésére. Elemeztük a chaperonok szerepét az öregedés során különös tekintettel az apoptózist gátló tulajdonságaikra. Az endoplazmatikus retikulum chaperonjai működési mechanizmusának számos új elemét tártuk fel egészséges, és krónikus stressznek kitett sejtekben. Számos új szempontot adtunk a chaperonok szerepének megértésére a sejt molekula-hálózataiban. Ezek legfontosabbikaként felismertük, hogy a hálózatok gyenge kölcsönhatásai részt vesznek minden komplex rendszer stabilizálásában. Kidolgoztunk és részben bizonyítottunk egy új gyógyszertervezési paradigmát, amely szerint a multi-target gyógyszerek hatékonyabbak, mint a jelenleg alkalmazott single-target gyógyszerek. Elvileg is új, rendkívül hatékony eljárás-családot dolgoztunk ki hálózatok átfedő moduljainak meghatározására és igen nagyméretű hálózatok hierarchikus ábrázolására. | We have identified a second, C-terminal nucleotide binding site, and an independent, taxol-binding site of the most abundant cytoplasmic stress protein, Hsp90. Both sites can be used as novel pharmacological targets in anticancer drug design. We demonstrated that the Hsp90 inhibitor drug candidates promote the lysis of the malignant cells by the immune system. We have discovered that chaperones contain a large amount of disordered regions and described the involvement of these regions in chaperone action. We analyzed the role of chaperones in aging with special reference to their anti-apoptotic effects. We identified several elements of chaperone action in the endoplasmic reticulum of normal cells and cells under chronic stress. We gave several new aspects to understand the role of chaperones in cellular networks. As the most important of these, we discovered that weak links stabilize all complex systems. We have developed and partially proved a novel drug design paradigm showing the efficiency of multi-target drugs. Lastly, we developed a novel, highly efficient group of methods to identify overlapping network modules and to visualize extremely large networks in a hiearachical (zoom-in) fashion

Superficial temporal artery access for carotid artery stenting: A case report

Percutaneous intervention of patients who suffer from generalized vascular disease is often a great challenge due to the limited accessibility of the access gates. We discuss the case of a 66-year-old man who presented with critical right internal carotid artery (ICA) stenosis after previous hospitalization due to stroke. In addition to arteria lusoria, the patient had known bilateral femoral amputation, occlusion of the left ICA and significant three-vessel coronary artery disease. After unsuccessful common carotid artery (CCA) cannulation from the right distal radial artery access, we successfully performed the diagnostic angiography and the planned right ICA-CCA intervention using superficial temporal artery (STA) puncture. We showed that STA access can be used as an alternative and additional access site for diagnostic carotid artery angiography and intervention when standard access sites alone are insufficient

Aging cellular networks: chaperones as major participants

We increasingly rely on the network approach to understand the complexity of cellular functions. Chaperones (heat shock proteins) are key "networkers", which have among their functions to sequester and repair damaged protein. In order to link the network approach and chaperones with the aging process, we first summarize the properties of aging networks suggesting a "weak link theory of aging". This theory suggests that age-related random damage primarily affects the overwhelming majority of the low affinity, transient interactions (weak links) in cellular networks leading to increased noise, destabilization and diversity. These processes may be further amplified by age-specific network remodelling and by the sequestration of weakly linked cellular proteins to protein aggregates of aging cells. Chaperones are weakly linked hubs [i.e., network elements with a large number of connections] and inter-modular bridge elements of protein-protein interaction, signalling and mitochondrial networks. As aging proceeds, the increased overload of damaged proteins is an especially important element contributing to cellular disintegration and destabilization. Additionally, chaperone overload may contribute to the increase of "noise" in aging cells, which leads to an increased stochastic resonance resulting in a deficient discrimination between signals and noise. Chaperone- and other multi-target therapies, which restore the missing weak links in aging cellular networks, may emerge as important anti-aging interventions.Comment: 7 pages, 4 figure

Protein-disulfide isomerase- and protein thiol-dependent dehydroascorbate reduction and ascorbate accumulation in the lumen of the endoplasmic reticulum.

The transport and intraluminal reduction of dehydroascorbate was investigated in microsomal vesicles from various tissues. The highest rates of transport and intraluminal isotope accumulation (using radiolabeled compound and a rapid filtration technique) were found in hepatic microsomes. These microsomes contain the highest amount of protein-disulfide isomerase, which is known to have a dehydroascorbate reductase activity. The steady-state level of intraluminal isotope accumulation was more than 2-fold higher in hepatic microsomes prepared from spontaneously diabetic BioBreeding/Worcester rats and was very low in fetal hepatic microsomes although the initial rate of transport was not changed. In these microsomes, the amount of protein-disulfide isomerase was similar, but the availability of protein thiols was different and correlated with dehydroascorbate uptake. The increased isotope accumulation was accompanied by a higher rate of dehydroascorbate reduction and increased protein thiol oxidation in microsomes from diabetic animals. The results suggest that both the activity of protein-disulfide isomerase and the availability of protein thiols as reducing equivalents can play a crucial role in the accumulation of ascorbate in the lumen of the endoplasmic reticulum. These findings also support the fact that dehydroascorbate can act as an oxidant in the protein-disulfide isomerase-catalyzed protein disulfide formation

Roles Played by the Na+/Ca2+ Exchanger and Hypothermia in the Prevention of Ischemia-Induced Carrier-Mediated Efflux of Catecholamines into the Extracellular Space: Implications for Stroke Therapy

The release of [3H]dopamine ([3H]DA) and [3H]noradrenaline ([3H]NA) in acutely perfused rat striatal and cortical slice preparations was measured at 37 °C and 17 °C under ischemic conditions. The ischemia was simulated by the removal of oxygen and glucose from the Krebs solution. At 37 °C, resting release rates in response to ischemia were increased; in contrast, at 17 °C, resting release rates were significantly reduced, or resting release was completely prevented. The removal of extracellular Ca2+ further increased the release rates of [3H]DA and [3H]NA induced by ischemic conditions. This finding indicated that the Na+/Ca2+ exchanger (NCX), working in reverse in the absence of extracellular Ca2+, fails to trigger the influx of Ca2+ in exchange for Na+ and fails to counteract ischemia by further increasing the intracellular Na+ concentration ([Na+]i). KB-R7943, an inhibitor of NCX, significantly reduced the cytoplasmic resting release rate of catecholamines under ischemic conditions and under conditions where Ca2+ was removed. Hypothermia inhibited the excessive release of [3H]DA in response to ischemia, even in the absence of Ca2+. These findings further indicate that the NCX plays an important role in maintaining a high [Na+]i, a condition that may lead to the reversal of monoamine transporter functions; this effect consequently leads to the excessive cytoplasmic tonic release of monoamines and the reversal of the NCX. Using HPLC combined with scintillation spectrometry, hypothermia, which enhances the stimulation-evoked release of DA, was found to inhibit the efflux of toxic DA metabolites, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL). In slices prepared from human cortical brain tissue removed during elective neurosurgery, the uptake and release values for [3H]NA did not differ from those measured at 37 °C in slices that were previously maintained under hypoxic conditions at 8 °C for 20 h. This result indicates that hypothermia preserves the functions of the transport and release mechanisms, even under hypoxic conditions. Oxidative stress (H2O2), a mediator of ischemic brain injury enhanced the striatal resting release of [3H]DA and its toxic metabolites (DOPAL, quinone). The study supports our earlier findings that during ischemia transmitters are released from the cytoplasm. In addition, the major findings of this study that hypothermia of brain slice preparations prevents the extracellular calcium concentration ([Ca2+]o)-independent non-vesicular transmitter release induced by ischemic insults, inhibiting Na+/Cl--dependent membrane transport of monoamines and their toxic metabolites into the extracellular space, where they can exert toxic effects

Endovascular Treatment for Anterior Circulation Large-Vessel Occlusion Ischemic Stroke with Low ASPECTS: a Systematic Review and Meta-Analysis

Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with Alberta Stroke Program Early CT Score (ASPECTS) 0-5 has not yet proven safe and effective by clinical trials. Objectives: The aim of the study was to assess whether EVT in AIS patients presenting with low ASPECTS is beneficial. Design: Systematic review and meta-analysis of available studies in accordance with the PRISMA statement. Data sources and methods: We have searched MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 28 May 2022 with the aim to calculate (1) modified Rankin scale (mRS) score 0-3 at 3 months, (2) mRS score 0-2 at 3 months, (3) symptomatic intracranial hemorrhage (sICH), and (3) mortality at 3 months. Results: Overall, 24 eligible studies were included in the meta-analysis, comprising a total of 2539 AIS patients with ASPECTS 0-5 treated with EVT. The pooled proportion of EVT-treated patients achieving mRS 0-3 at 3 months was calculated at 38.4%. The pooled proportion of EVT-treated patients achieving mRS 0-2 at 3 months was 25.7%. Regarding safety outcomes, sICH occurred in 12.8% of patients. The 3-month pooled mortality was 30%. In pairwise meta-analysis, patients treated with EVT had a higher likelihood of achieving mRS 0-3 at 3 months compared with patients treated with best medical therapy (BMT, OR: 2.41). sICH occurred more frequently in EVT-treated patients compared with the BMT-treated patients (OR: 2.30). Mortality at 3 months was not different between the two treatment groups (OR: 0.71). Conclusion: EVT may be beneficial for AIS patients with low baseline ASPECTS despite an increased risk for sICH. Further data from randomized-controlled clinical trials are needed to elucidate the role of EVT in this subgroup of AIS patients. Registration: The protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO; Registration Number: CRD42022334417.info:eu-repo/semantics/publishedVersio

Participation of Low Molecular Weight Electron Carriers in Oxidative Protein Folding

Oxidative protein folding is mediated by a proteinaceous electron relay system, in which the concerted action of protein disulfide isomerase and Ero1 delivers the electrons from thiol groups to the final acceptor. Oxygen appears to be the final oxidant in aerobic living organisms, although the existence of alternative electron acceptors, e.g. fumarate or nitrate, cannot be excluded. Whilst the protein components of the system are well-known, less attention has been turned to the role of low molecular weight electron carriers in the process. The function of ascorbate, tocopherol and vitamin K has been raised recently. In vitro and in vivo evidence suggests that these redox-active compounds can contribute to the functioning of oxidative folding. This review focuses on the participation of small molecular weight redox compounds in oxidative protein folding