A Portrait of the GET Pathway as a Surprisingly Complicated Young Man

Many eukaryotic membrane proteins have a single C-terminal transmembrane domain that anchors them to a variety of organelles in secretory and endocytic pathways. These tail-anchored (TA) proteins are post-translationally inserted into the endoplasmic reticulum by molecular mechanisms that have long remained mysterious. This review describes how, in just the past 5 years, intense research by a handful of laboratories has led to identification of all the key components of one such mechanism, the guided entry of TA proteins (GET) pathway, which is conserved from yeast to man. The GET pathway is both surprisingly complicated and yet more experimentally tractable than most other membrane insertion mechanisms, and is rapidly revealing new fundamental concepts in membrane protein biogenesis.Molecular and Cellular Biolog

The poetics of suffering and refuge in newer Serbian literature of Kosovo and Metohija

In the paper, we talk about the newer Serbian literature of Kosovo and Metohija which deals with the problem of persecution and fleeing of people from their home places and hearths. Such poetics has been especially present during the last few decades as a proof of massive affliction. Partially colored by neo-patriotic nuances, this kind of literature has more epic qualities than lyric ones; it is more of an expression of general suffering and sorrow, than sadness over personal fat

ER Targeting and Insertion of Tail-Anchored Membrane Proteins by the GET Pathway

Hundreds of eukaryotic membrane proteins are anchored to membranes by a single transmembrane domain at their C-terminus. Many of these tail-anchored (TA) proteins are post-translationally targeted to the endoplasmic reticulum (ER) membrane for insertion by the Guided-Entry of TA protein insertion (GET) pathway. In recent years most of the components of this conserved pathway have been biochemically and structurally characterized. Get3 is the pathway targeting factor that utilizes nucleotide-linked conformational changes to mediate the delivery of TA proteins between the GET pre-targeting machinery in the cytosol and the transmembrane pathway components in the ER. Here we focus on the mechanism of the yeast GET pathway and make a speculative analogy between its membrane insertion step and the ATPase-driven cycle of ABC transporters.Molecular and Cellular Biolog

Timing matters: species-specific interactions between spawning time, substrate quality, and recruitment success in three salmonid species

Substratum quality and oxygen supply to the interstitial zone are crucial for the reproductive success of salmonid fishes. At present, degradation of spawning grounds due to fine sediment deposition and colmation are recognized as main factors for reproductive failure. In addition, changes in water temperatures due to climate change, damming, and cooling water inlets are predicted to reduce hatching success. We tested the hypothesis that the biological effects of habitat degradation depend strongly on the species-specific spawning seasons and life-history strategies (e. g., fall-vs. spring-spawners, migratory vs. resident species) and assessed temperature as an important species-specific factor for hatching success within river substratum. We studied the species-specific differences in their responses to such disturbances using egg-to-fry survival of Danube Salmon (Hucho hucho),resident brown trout (Salmo trutta fario), and migratory brown trout (Salmo trutta lacustris) as biological endpoint. The egg incubation and hatching success of the salmonids and their dependence on temperature and stream substratum quality were compared. Hatching rates of Danube salmon were lower than of brown trout, probably due to higher oxygen demands and increased interstitial respiration in spring. Increases in maximum water temperature reduced hatching rates of resident and migratory brown trout (both fall-spawners) but were positively correlated with hatching rates of Danube salmon (a spring-spawner). Significantly longer incubation periods of resident and migratory brown trout coincided with relatively low stream substratum quality at the end of the egg incubation. Danube salmon seem to avoid low oxygen concentrations in the hyporheic zone by faster egg development favored by higher water temperatures. Consequently, the prediction of effects of temperature changes and altered stream substratum properties on gravel-spawning fishes and biological communities should consider the observed species-specific variances in life-history strategies to increase conservation success

High incidence of multiresistant bacterial isolates from bloodstream infections in trauma emergency department and intensive care unit in Serbia

We investigated the incidence of bloodstream infections (BSIs) in trauma emergency department (ED) and intensive care unit (ICU), to assess ED- and ICU-related predictors of BSI and to describe the most common bacteria causing BSI and their antimicrobial resistance markers. A prospective study was conducted in two trauma ICUs of the ED of Clinical Center of Serbia. Overall, 62 BSIs were diagnosed in 406 patients, of which 13 were catheter-related BSI (3.0/1,000 CVC-days) and 30 BSIs of unknown origin, while 15% were attributed to ED CVC exposure. Lactate ≥2 mmol/L and SOFA score were independent ED-related predictors of BSI, while CVC in place for >7 days and mechanical ventilation >7 days were significant ICU-related predictors. The most common bacteria recovered were Acinetobacter spp., Klebsiella spp., and Pseudomonas aeruginosa. All Staphylococcus aureus and coagulase-negative staphylococci isolates were methicillin-resistant, whereas 66% of Enterococcus spp. were vancomycin-resistant. All isolates of Enterobacteriaceae were resistant to third-generation cephalosporins, whereas 87.5% of P. aeruginosa and 95.8% of Acinetobacter spp. isolates were resistant to carbapenems. ED BSI contributes substantially to overall ICU incidence of BSI. Lactate level and SOFA score can help to identify patients with higher risk of developing BSI. Better overall and CVC-specific control measures in patients with trauma are needed

Einfluss von Vetiveröl auf Speichelcortisol und Befindlichkeit

Im Rahmen der vorliegenden Arbeit wurden die Auswirkungen des Vetiveröls auf den Speichelcortisolgehalt und die subjektive Befindlichkeit untersucht. Es wurde damit versucht, die aphrodisierende Wirkung des Vetiveröls zu belegen. Es nahmen 50 Probanden an der Studie teil, 25 Frauen und 25 Männer. Zusätzlich wurden die Effekte auf das Geschlecht untersucht. Der Aufbau der durchgeführten Studie basiert auf der Sandelholzöl-Geraniumöl Studie (Rameder, 2008; Angerer, Bichl, 2009). Während der Sitzungen der Sandelholzöl-Geraniumöl Studie standen die Probanden entweder unter dem Einfluss von Sandelholzöl, Geraniumöl oder Raumluft. Als Referenzwerte für die vorliegende Studie dienten die Luft- und Geraniumöldaten. Es wurde eine Sitzung mit jedem Probanden durchgeführt, während welcher das Vetiveröl mit dem Beduftungssystem von Venta® im Raum versprüht wurde. Die Teilnehmer wurden erst zum Schluss der Sitzung über die Anwesenheit eines Duftes informiert. Jede Sitzung umfasste zwei Durchgänge, in welchen die Probanden die Attraktivität von Frauen- und Männerbildern am Computer bewerteten. Zu Beginn und am Ende der Sitzung wurde der Blutdruck gemessen und ein Fragebogen zur Erhebung der subjektiven Befindlichkeit ausgefüllt. Während der Durchgänge wurden die physiologischen Parameter Hauttemperatur, Hautleitfähigkeit, Aktivität der Nackenmuskulatur und die Atem-, Herz- und Lidschlagfrequenz aufgezeichnet. Jeder Proband gab insgesamt drei Speichelproben zur Untersuchung des Speichelcortisolgehaltes ab. Die Auswertung des Speichelcortisols erfolgte mittels ELISA. Mittels ANOVA wurde die statistische Analyse durchgeführt. Für den Parameter Speichelortisol wurden keine signifikanten Ergebnisse festgestellt. Die statistische Analyse der Daten des Befindlichkeitsfragebogens ergab für 50 Probanden im Vergleich von Vetiveröl und Luft signifikante Ergebnisse für die Parameter Anspannung, Müdigkeit und Traurigkeit. Betrachtet man die Daten der Analyse bezogen auf das Geschlecht, so sind die Auswirkungen auf weiblichen Probanden stärker ausgeprägt als auf männlichen Probanden. Hinsichtlich der statistischen Daten von Vetiveröl und Geraniumöl mit 50 Probanden wurden signifikante Ergebnisse für die Parameter Anspannung, Verwirrtheit, Müdigkeit und Traurigkeit festgestellt. In Bezug auf das Geschlecht wurden signifikante Ergebnisse der Frauen für die Parameter Müdigkeit, Anspannung und Vitalität festgestellt. Für den Parameter Verwirrtheit wurde ein Trend festgestellt. In der Vergleichsstudie standen nur 13 Probanden in der ersten Sitzung unter Einfluss von Raumluft und 21 Probanden unter Einfluss von Geraniumöl. Das war der Grund dafür, dass zusätzlich eine statistische Analyse mit 13 und 21 Vetiverölprobanden im Vergleich zu 13 Luftprobanden und 21 Geraniumölprobanden durchgeführt wurde. Hinsichtlich der statistischen Analyse mit den Daten der 13 Probanden wurde ein signifikantes Ergebnis für die Müdigkeit festgestellt. Die statistische Analyse von 21 Probanden ergab signifikante Ergebnisse für die Parameter Müdigkeit und Vitalität. Für den Parameter Traurigkeit wurde ein Trend festgestellt. Betrachtet man die Ergebnisse der Parameter Hedonik und Bekanntheit, so ergab sich ein signifikantes Ergebnis für die Bekanntheit. Das Geraniumöl wurde als signifikant bekannter eingestuft. In dieser Arbeit wurden signifikante Unterschiede der Duftbedingugnen auf die menschliche Psyche festgestellt. Eine aphrodisierende Wirkung des Vetiveröls konnte mit dieser Studie nicht belegt werden.This study analyzes the effects of vetiver oil on salivary cortisol level, as well as the effects on the emotional state of the participants. The study has been conducted under specific conditions, which included the participation of 50 people, 25 male and 25 female. Additionally, gender effects were analyzed. The aim was to prove the aphrodisiac effects of the vetiver oil. The set-up of the study is consistent with the study of New Caledonian sandalwood oil and geranium oil. This study consisted of total three sessions per each person, while the vetiver oil study consisted of only one session per person. In the first study the subjects were either under the influence of sandalwood oil or geranium oil or odorless air. The data acquired under the influence of the odorless air and the geranium oil were used as reference values. During the session, vetiver oil was volatilized via Venta® equipment. The participants were told only at the end of the study that an odor had in fact been present. Each session consisted of two trials, in which the participants assessed the attractiveness of the male and female images on the computer. Moreover at the beginning and at the end of each trial, the participants had their blood pressure measured, and they also had to fill in a survey stating their emotional state. During the session, some physiological parameters were assessed, such as skin temperature, skin conductance level, neck muscle activity, heart rate, breathing rate and blink rate. Each of the participants turned in three saliva samples for cortisol analyzing. The statistical analysis was accomplished using ANOVA. No significant results could be demonstrated for salivary cortisol. Statistical analysis of the mood-questionnaire of the participants, evidenced some significant results when comparing the effects of vetiver oil and of odorless air on tension, fatigue and depression. Concerning gender-releated statistical analysis, the effects of the vetiver oil are significantly higher for women than for men. Concernig the statistical results for the vetiver oil and geranium oil, which was conducted on 50 participants, the vetiveroil group executed significant results in the parameters of tension, fatigue, confusion and depression. It was also demonstrated that the fatigue, vigor and tension significantly changed with women who were under the influence of the vetiver oil. There was an established trend for the confusion parameter. During the New Caledonian sandalwood oil and geranium oil study, only 13 of the participants were under the influence of odorless air during the first visit, while 21 of the participants were under influence of the geranium oil. This was a reason for accomplishing a statistical analysis with the 13 and 21 of the vetiver participants and to compare them with the 13 participants who were under the influence of odorless air and 21 of the participants who were under the influence of geranium oil. Concernig the results for the 13 subjects, there is a significant result concerning fatigue. A statistical analysis conducted on the 21 participants evidenced significant results for fatigue and vigor. There was also an established trend for the depression parameter. A significant result could be demonstrated for the recognition parameter: The participants appraised the geranium oil much more familiar. During this study, some significant effects could be demonstrated for vetiver oil, compared to odorless air and geranium oil. An aphrodisiac effect could not be found during this study

Prevalence of and factors associated with obstructive sleep apnea in a cohort of adults with long duration type 1 diabetes mellitus

Chronic health conditions like diabetes and sleep disorders have been increasing. Previous research showed that diabetes and sleep disorders are interrelated. The majority of studies examining this relationship focused on type 2 diabetes. Although a relationship between sleep disorders and type 1 diabetes (T1D) has been studied, investigations have been limited to youth and small samples. We, therefore, aimed to assess the prevalence, overall and gender-specific, and correlates, of obstructive sleep apnea (OSA) risk in an adult cohort with long-standing T1D. A total of 170 individuals with T1D attending the 25-year follow-up of the Pittsburgh Epidemiology of Diabetes Complications study who completed an OSA screening tool, the Berlin Questionnaire (BQ), were included in this cross-sectional analysis. Those scoring positively on the BQ and/or reported a previous OSA diagnosis were classified as being at high OSA risk. The OSA risk prevalence was 25.9% (25.0% among men, 26.6% among women). High versus low-OSA-risk individuals differed univariately with respect to markers of obesity, systolic blood pressure, estimated glucose disposal rate, lipid profile, and smoking history, although no differences were observed in hemoglobin A1c. In the final multivariable model, adjusting for sex and diabetes duration, body mass index (BMI) (directly, p=0.01), high-density lipoprotein (HDL) (inversely, p=0.03), and smoking history (directly, p=0.04) correlated with OSA risk. In gender-specific analyses, adjusting for diabetes duration, BMI (directly, p=0.007) and HDL (inversely, p=0.03) were also associated with OSA risk in women, while diastolic blood pressure (p=0.01) and smoking history (p=0.04) were positive OSA correlates in men. Our findings suggest that the prevalence of high OSA risk in adults with long-standing T1D is comparable to that in the general population. Given that both OSA screening tools and treatment are widely available, identifying high OSA risk among individuals already burdened with a serious chronic disease is of public health importance. Indeed, modifiable risk factors were independently associated with OSA risk in this study, suggesting that the adoption of a healthier lifestyle may reduce OSA risk in T1D, improving the wellbeing and reducing the subsequent risk of further complication development. Future prospective cohorts should be conducted to explore this hypothesis