👤 Siegfried Perz

Transport along the endolysosomal system requires multiple fusion events at early and late endosomes. Deletion of several endosomal fusion factors, including the Vac1 tether and the Class C core vacuole/endosome tethering (CORVET) complex-specific subunits Vps3 and Vps8, results in a class D vps phenotype. As these mutants have an apparently similar defect in endosomal transport, we asked whether CORVET and Vac1 could still act in distinct tethering reactions. Our data reveal that CORVET mutants can be rescued by Vac1 overexpression in the endocytic pathway but not in CPY or Cps1 sorting to the vacuole. Moreover, when we compared the ultrastructure, CORVET mutants were most similar to deletions of the Rab Vps21 and its guanine nucleotide exchange factor Vps9 and different from vac1 deletion, indicating separate functions. Likewise, CORVET still localized to endosomes even in the absence of Vac1, whereas Vac1 localization became diffuse in CORVET mutants. Importantly, CORVET localization requires the Rab5 homologs Vps21 and Ypt52, whereas Vac1 localization is strictly Vps21-dependent. In this context, we also uncover that Muk1 can compensate for loss of Vps9 in CORVET localization, indicating that two Rab5 guanine nucleotide exchange factors operate in the endocytic pathway. Overall, our study reveals a unique role of CORVET in the sorting of biosynthetic cargo to the vacuole/lysosome. Show less

Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38,991 subjects of European ancestry, estimating the association between age-, sex- and body mass-adjusted RR interval (inverse heart rate) and approximately 2.5 million markers. Results with P < 5 × 10(-8) were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain approximately 0.7% of RR interval variance. A multivariant regression model including 20 variants with P < 10(-5) increased the explained variance to 1.6%, suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care. Show less

In Poland approximately 33% adults are active smokers. Both active smoking and passive exposition to tobacco smoke leads to serious diseases and causes many other problems. This is why the decrease of smoking prevalence seems to be one of the most important targets of contemporary medicine. In this task the attitude of medical staff plays a great role (prevention, education, behaviour of a medical employee as a positive example). The research was carried out among 48 employees of Regional Station of Ambulance Service in Poznan (16 physicians, 19 medical rescuers and 13 nurses). The group comprised 21 women and 27 men. The investigative tool was a questionnaire concerning smoking, passive exposition to tobacco smoke and attitude of the examined persons towards smoking. We found that smoking prevalence in the investigated group considerably exceeds the average values for Polish population (particularly the number of smoking women) whereas passive exposition to tobacco smoke affects everyone in this group. In the opinion of the examined people the main factors inducing and maintaining tobacco smoking are: addiction, pleasure connected with smoking or influence of someone's company. In a case of medical personnel tobacco smoking (similarly to other behaviours which are harmful for someone's health) weakens the authority of a health care provider as an example of health promotion. Show less

Prevalence of tobacco smoking among young people is one of the most important aspects in prevention of smoking and smoking-related diseases. The aim of this study was assessment of pharmacy students' exposition to tobacco smoke (active and passive smoking) and searching for circumstances promoting tobacco smoking and exposition to ETS (environmental tobacco smoke). In the examined cohort of 161 students we found 37 smokers (23%; 21.2% women and 31% men), among them 14 (8.7%) everyday smokers. ETS affected 155 persons (96.3%) and usually took place in a circle of friends. The most common factors promoting tobacco smoking were: pleasure connected with smoking, smoking as a support in stress situation or as a facilitation of society functioning and getting to know new friends. We must emphasize again the leading role of prevention of smoking initiation in young people in all preventive activities. Show less

Harmful influence of tobacco smoke on mother and child comprises many effects, among which the best known are: impaired fecundability, increased risk of pregnancy and perinatal period complications, increased morbidity of neonates and respiratory, circulatory and neurological disorders in neonates, infants and older children. The aim of this study was to assess smoking prevalence among pregnant women and young mothers and to assess the degree of exposition of infants to environmental tobacco smoke (ETS). The study was carried out among 74 women after delivery in the F. Raszeja City Hospital in Poznan, Poland, between December 2005 and May 2006. Smoking prevalence among pregnant women was 8.1% (women with high educational level--2.6%, others--14.3%). Smoking prevalence among mothers within the first year after delivery was 4.05% (women with high educational level--0%, others--8.6%). 17.6% infants (10.3% children of mothers with high educational level and 25.7% children delivered by the other mothers) were exposed to ETS because of smokers at home (other than mother); 10 infants exposed to ETS had non-smoking mother. Show less

Sudden infant death syndrome (SIDS) means the sudden death of an infant which is unexpected by history and in which an examination of the death scene and a thorough postmortem examination fails to reveal an adequate cause of death. Etiology of this syndrome is unknown but many risk factors were identified; the most important and preventable risk factors are prone sleeping position and influence of tobacco smoke (both smoking by pregnant woman and environmental tobacco smoke (ETS) near child's bed). The aim of this study was to assess the prevalence of smoking among women (also during pregnancy) and exposure of neonates and infants to ETS, to establish what circumstances are likely to make smoking woman stop smoking and to examine women's knowledge concerning risk factors of SIDS (mainly influence of tobacco smoke). The study comprised 61 women, aged 24 to 47, among them 35 nurses and 26 women without any medical education. The average percentage of smoking women was near 25% but among nurses was up to 30%. The prevalence of smoking during pregnancy was 6%. We identified high risk of ETS influence among both women and their children. The most important cause of smoking cessation was pregnancy. Among arguments for smoking cessation the risk of SIDS takes an important place. Women's knowledge about risk factors of SIDS (among them influence of tobacco smoke) and activity of physicians and midwifes to educate women as for this risk factors are unsatisfactory. Show less