The formation of endoplasmic reticulum-plasma membrane contact sites in mammalian cells

Das endoplasmatische Retikulum (ER) ist in seiner Morphologie verschiedenartig. Es setzt sich aus plattenförmigen und tubulären Strukturen zusammen. Die verschiedenen Domänen des ERs erfüllen vielfache Funktionen u.a. in der kotranslationalen Proteintranslokation, der Lipidsynthese, der Qualtitätskontrolle und dem Protein- und Lipidtransport zu unterschiedlichen Organellen. Das ER steht in engem Kontakt mit anderen Organellen, um Überleben und Wachstum einer Zelle zu gewährleisten. Zusätzlich bildet das ER Kontakte mit der Plasmamembran (PM) aus. An diesen Kontakten finden Lipidtransfer und Kopplung von Ca2+-Signalen statt. Eine Komponente des kortikalen ERs in der Bäcker-Hefe ist das integrale Membranprotein Ist2. Die Sortierung von Ist2 in das kortikale ER erfolgt mit Hilfe seines kortikalen Sortierungssignals (CSS), das an Lipide der PM bindet. Da bisher nicht bekannt war, ob Ist2 im kortikalen ER verbleibt oder durch einen unkonventionellen Weg zur Plasmamembran gelangt, habe ich die Lokalisation von Ist2 in mammalischen Zellen untersucht. Meine Ergebnisse demonstrieren, dass Ist2 das ER nicht verläßt und dort periphere Domänen ausbildet, die in enger Nachbarschaft zur PM liegen. Um die Merkmale dieser peripheren ER-Strukturen weiter zu analysieren, habe ich mammalische Typ1-Membranproteine mit dem CSSIst2 markiert und deren Lokalisation untersucht. Durch die Interaktion des CSSIst2 mit Lipiden der PM wurden alle getesteten Chimären zu den peripheren ER-Strukturen rekrutiert. Weiterhin konnte ich zeigen, daß diese peripheren ER-Strukturen statisch und mit dem restlichen ER verbunden sind. Neben dem Hefeprotein Ist2 sind die mammalischen Proteine STIM1 und STIM2 ebenfalls in der Lage, ER-PM-Kontaktstellen zu bilden. STIM-Proteine haben ihre Funktion in der Signalverstärkung während des Speicher-abhängigen Ca2+-Eintritts. Sie erkennen Ca2+-Konzentrationen durch ihre N-terminalen EF-Hand-Domänen. Nach Ca2+-Depletion des ERs multimerisieren sie und formen ER-PM-Kontaktstellen, an denen sie mit dem Ca2+-Kanal der PM, Orai1, interagieren und diesen aktivieren. Darüber hinaus habe ich den molekularen Mechanismus der Ausbildung von ER-PM-Kontaktstellen aufgedeckt. Durch in vitro Liposomen-Bindungsstudien habe ich gezeigt, dass die C-Termini von STIM1 und STIM2 mittels ihrer Lysin (K)-reichen Domänen an Lipide der PM binden. Diese Ergebnisse verdeutlichen, daß die Ausbildung der ER-PM-Kontaktstellen von der Expression einen integralen membranenprotein mit einem PM-Lipid-Bindungssignal abhängig ist. Da für das STIM1-Protein bereits eine Lokalisation an der Zelloberfläche demonstriert worden war, habe ich seine Retention im ER untersucht. Dabei konnte ich zwei Mechanismen identifizieren. Der erste Mechanismus beruht auf dem Zurückhalten des STIM1-Proteins im ER über mehrere Di-Arginin ER-Retentionssignale. Der zweite Mechanismus ist abhängig von der cytosolischen Ca2+-Konzentrationen. Meine Ergebnisse zeigen, dass die Depletion von cytosolischem Ca2+ den Transport von STIM1 an die Zelloberfläche fördert, wo STIM1 Orai1 aktiviert. Ausgehend von meinen Daten erkennt STIM1 indirekt das cytosolische Ca2+ durch seine K-reiche Domäne, die Ca2+ im Komplex mit Calmodulin bindet. Somit integriert STIM1 Ca2+-Signale im ER und im Cytosol

Psikolojik Şiddetin Örgütsel Bağliliğa Etkisi1 The Effect of Mobbing on Organizational Commitment

Günümüz yoğun rekabet koşulları, gelişen teknolojiye uyum sağlayabilmek ve hızla artan nüfusun ihtiyaçlarının karşılanabilmesi gibi sebeplerle insanlar her geçen gün çalışma ortamında daha fazla vakit geçirmek zorunda kalmaktadır. Çalışma ortamında geçirilen fazladan saatler karşılıklı çatışmaları arttırmakta ve stresi yükseltmektedir. Yapılan çalışmaların sonuçları ise stresin psikolojik şiddetin temel nedenlerinden biri olduğunu göstermektedir. Sağlık çalışanları çalışma koşullarından ve yaptıkları işin öneminden dolayı stres olgusunu oldukça fazla yaşamaktadırlar. Bu araştırma ile sağlık çalışanlarının psikolojik şiddete maruz kalmalarının örgütsel bağlılıklarına etkisi belirlenmeye çalışılmıştır. Araştırmanın evrenini Ankara ilindeki sağlık örgütlerinde görev alan sağlık çalışanları oluşturmuştur. Tüm evrene ulaşmak mümkün olmadığından basit tesadüfi örneklem yöntemiyle belirlenen 390 kişilik örneklem grubu üzerinden hareket edilmiştir. Araştırmanın problemini desteklemek üzere yapılan analizler sonucunda sağlık çalışanlarının maruz kaldıkları psikolojik şiddet artarken devamlılık bağlılıkları da artmakta ancak duygusal bağlılıkları ve normatif bağlılıkları azalmaktadır. Due to today's intense competition conditions, adaptation to developing technology and meeting the needs of rapidly growing population, people are forced to spend more time in working environment. The extra hours spent in the working environment increase the conflicts and the stress. The results of the studies show stress is the basic cause of mobbing. Health workers are experiencing a great deal of stress due to their working conditions and the importance of their job. This research was conducted with the purpose of determining the effect of psychological violence on organizational commitment of healthcare workers. This research has targeted the healthcare workers located in the province of Ankara. The study was limited to a coincidental sample group of 390 health workers. The final analysis shows that, with the increase of psychological violence exposure, it has been observed that while the healthcare workers’ continuance commitment increases their emotional and normative commitment decreases

A possible optical counterpart of the X-ray source NuSTARJ053449+2126.0

In this work, we report the observation of a possible optical counterpart to the recently discovered X-ray source NuSTAR J053449+2126.0. To search for an optical counterpart of NuSTAR J053449+2126.0 (J0534 in short), we observed the source with the 1.5-m Telescope (RTT150). Using the B, V, R, and I images of J0534, we detected the possible optical counterpart of J0534 and determined, based on our spectral analysis, the source distance for the first time. J0534 could be a high-redshift member of an Active Galactic Nucleus (AGN) sub-group identified as a quasar. Our analysis favours an accreting black hole of mass $\sim 7\times 10^8 M_{\odot}$ as a power supply for the quasar in J0534. Further observations in optical and other wavelengths are needed to confirm its nature.Comment: 7 pages, 4 figure

Deaf athlete: is there any difference beyond the hearing loss?

Regular physical activity and sport is important for enhanced physical fitness and skill performance of deaf athletes. However there are few data in the literature about their medical considerations. In this study we aimed to determine the morphological findings and cardiac status of the deaf athletes and compare them with the normal ones. Thirty deaf and twenty-two normal male athletes without cardiovascular diseases participated in the study. Transthoracic echocardiography and exercise stress testing were performed. Tissue Doppler imaging (TDI)-derived myocardial performance index (MPI) was also evaluated. VO2 max and heart rate recovery were calculated after exercise stress testing. Total cholesterol, LDL and trigliseride levels were significantly increased in the deaf athletes, but they were still found to be in normal ranges according to age and risk factor profile (p< 0.05). End-diastolic diameter and left ventricular mass index were found to be significantly increased in the controls when compared with the deaf athletes (p< 0.001). Heart rate recovery at 1 minute did not show any difference in the deaf group when compared with the control group (p> 0.05). MPI calculated from TDI-derived variables was found to be 0.41±0.073 in the deaf group and 0.46±0.061 in the controls respectively and significantly decreased in the deaf (p < 0.05). Beyond having a hearing loss, the deaf athletes have many cardiac structural and functional differences from their normal counterparts. The factors that give rise to these differences have to be revealed by further research

Factors associated with increased carotid intima-media thickness and being nondipper in nonobese and normotensive young patients affected by PCOS

Polycystic ovary syndrome (PCOS) is characterized by chronic unovulation, hyperandrogenism, and insulin resistance. We evaluated factors that affect nondipper status during 24-hour ambulatory blood pressure monitoring (ABPM) and carotid intima-media thickness (cIMT) in PCOS. Forty-two nonobese women newly diagnosed as PCOS and 32 healthy women were included. After biochemical and hormonal measurements, the ovaries were imaged by pelvic ultrasonography and cIMT was measured by B-mode ultrasonography. A 24-hour ABPM was performed thereafter. Carotid IMT and the ratio of nondippers were elevated compared with controls. Homeostasis model assessment insulin resistance index (HOMA-IR) and low-density lipoprotein cholesterol (LDL-C) were found to be related with being a nondipper in PCOS. None of the parameters evaluated were found to correlate with cIMT. In conclusion, patients with PCOS had increased nondipping ratios and cIMT when compared with controls. Insulin resistance and LDL cholesterol are factors that are related to diurnal variation in normotensive and young patients with PCOS

Association of total serum antioxidant capacity with the Tei index in echocardiography in patients with microvascular angina

Objectives Cardiac syndrome X (CSX) is a conditioncharacterized by exercise-induced chest pain that occursconsidering a normal coronary angiogram. We aimed toinvestigate the total serum antioxidant capacity (TAC) andbiventricular global functions using echocardiography inpatients with CSX.Patients and methods The study population included 55patients with typical anginal symptoms and a positiveexercise stress test, or ischemia in myocardial perfusionscintigraphy and normal coronary arteries detectedangiographically, and 49 healthy volunteers with atypicalchest pain and a negative stress test. TAC was assessedfrom blood samples. Transthoracic echocardiography wasperformed for the entire study population. The Tei index wascalculated using the formula IVCT+IVRT/ET.Results TAC was found to be significantly lower in the CSXgroup compared with the control group (0.70 ± 0.37 vs.1.5± 0.30, respectively, P1.77 mmol/l), it was found that the Tei indexwas higher in the decreased TAC group compared with theother groups (0.66 ± 0.18 vs. 0.49 ± 0.10 and0.46± 0.13 mmol/l, P<0.001, respectively).Conclusion Our study suggested that TAC wassignificantly decreased in CSX patients and decreasedantioxidant levels were related to impaired Tei index inechocardiography in patients with microvascularangina. Coron Artery Dis 26:620–625 Copyright © 2015Wolters Kluwer Health, Inc. All rights reserved

Retrospektivna analiza graničnih tumora jajnika: ishodi u jednom centru

We wanted to discuss our experiences in the approach to borderline ovarian tumors, which constitute a group different from epithelial ovarian tumors with respect to their biological structure in line with retrospective information gathered from our cases. A total of 25 patients operated on for the indication of adnexal masses diagnosed as borderline ovarian tumors based on frozen section results were included in our study. Patient age, tumor diameter, tumor markers and surgeries performed were discussed in the light of the literature. Statistical analyses were performed using the SPSS software. The patient mean age was 43.84±11.34 years. The mass was localized in the right (n=13), left (n=11) or both (n=1) adnexal regions. The mean tumor diameter was 12.9±5.84 cm. Histopathologic examination established the diagnosis of serous borderline (n=14 patients) and mucinous borderline (n=11) ovarian tumors. Although the results of our study are consistent with current literature data, a greater number of current studies should be performed on borderline ovarian tumors, which are defined as a class of tumors different from epithelial ovarian tumors.Želja nam je opisati naša iskustva u pristupu graničnim tumorima jajnika kao skupini tumora koji se razlikuju od epitelnih tumora jajnika prema biološkoj strukturi, sukladno retrospektivnim podacima prikupljenim iz naših slučajeva. U istraživanje je bilo uključeno 25 bolesnica operiranih pod indikacijom adneksnih tvorevina dijagnosticiranih kao granični tumori jajnika na osnovi rezultata dobivenih iz zamrznutih uzoraka. Prikazani su sljedeći podaci bolesnica: dob, promjer tumora, tumorski biljezi i izvedeni operativni zahvati, u odnosu na literaturne podatke. Statistička analiza je provedena primjenom programa SPSS. Srednja dob bolesnica bila je 43,84±11,34 godine. Tumorska masa bila je smještena u desnoj (n=13) ili lijevoj (n=11) adneksnoj regiji, a kod jedne bolesnice u objema adneksnim regijama. Srednji promjer tumora bio je 12,9±5,84 cm. Histopatološkom analizom postavljena je dijagnoza seroznog graničnog (n=14) i mucinoznog graničnog (n=11) tumora jajnika. Iako su rezultati ovoga istraživanja sukladni literaturnim podacima, potrebno je provesti veći broj studija graničnih tumora jajnika, koji se definiraju kao vrsta tumora različita od epitelnih tumora jajnika

Nutritional status and severity of coronary artery disease

Objective The aim of this study is to evaluate the association between Nutritional Risk Index (NRI), a simple tool to assess nutritional status, and coronary artery disease severity and complexity in patients undergoing coronary angiography. Methods This study is a retrospective analysis of 822 patients undergoing coronary angiography. Patients with previous revascularization were excluded. Gensini and SYNTAX scores were calculated according to the angiographic images to determine atherosclerosis severity. NRI was calculated as follows: NRI = [15.19 × serum albumin (g/dl)] + [41.7 × (body weight/ideal body weight)]. In patients ≥65 years of age, Geriatric NRI (GNRI) was used instead of NRI. GNRI was calculated as follows: GNRI = [14.89 × serum albumin (g/dl)] + [41.7 × (body weight/ideal body weight)]. Patients were then divided into three groups as previously reported: NRI < 92, NRI 92–98 and NRI > 98. Gensini and SYNTAX scores were compared between three groups. Results The mean age of study population was 61.9 ± 11.1 years. NRI 98 was measured in 212, 321 and 289 patients, respectively. There was no difference regarding to sex, BMI, smoking, hypertension and diabetes mellitus between three groups. Patients with NRI < 92 had the highest mean Gensini score than the patients with NRI 92–98 and NRI > 98 (38.0 ± 40.6 vs. 31.17 ± 42.4 vs. 25.8 ± 38.4, P = 0.005). Also patients with NRI < 92 had the highest mean SYNTAX score than the patients with NRI 92–98 and NRI > 98 (11.8 ± 12.9 vs. 9.3 ± 12.4 vs. 7.7 ± 11.8, P = 0.001). Also, Gensini score of ≥20 and high SYNTAX score of ≥33 were associated with lower NRI (P < 0.001 and P < 0.001, respectively). Conclusion In our study, nutritional status evaluated by the NRI was associated with more extensive and complex coronary atherosclerosis in patients undergoing coronary angiography