Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiae

Due to its genetic tractability and increasing wealth of accessible data, the yeast Saccharomyces cerevisiae is a model system of choice for the study of the genetics, biochemistry, and cell biology of eukaryotic lipid metabolism. Glycerolipids (e.g., phospholipids and triacylglycerol) and their precursors are synthesized and metabolized by enzymes associated with the cytosol and membranous organelles, including endoplasmic reticulum, mitochondria, and lipid droplets. Genetic and biochemical analyses have revealed that glycerolipids play important roles in cell signaling, membrane trafficking, and anchoring of membrane proteins in addition to membrane structure. The expression of glycerolipid enzymes is controlled by a variety of conditions including growth stage and nutrient availability. Much of this regulation occurs at the transcriptional level and involves the Ino2–Ino4 activation complex and the Opi1 repressor, which interacts with Ino2 to attenuate transcriptional activation of UASINO-containing glycerolipid biosynthetic genes. Cellular levels of phosphatidic acid, precursor to all membrane phospholipids and the storage lipid triacylglycerol, regulates transcription of UASINO-containing genes by tethering Opi1 to the nuclear/endoplasmic reticulum membrane and controlling its translocation into the nucleus, a mechanism largely controlled by inositol availability. The transcriptional activator Zap1 controls the expression of some phospholipid synthesis genes in response to zinc availability. Regulatory mechanisms also include control of catalytic activity of glycerolipid enzymes by water-soluble precursors, products and lipids, and covalent modification of phosphorylation, while in vivo function of some enzymes is governed by their subcellular location. Genome-wide genetic analysis indicates coordinate regulation between glycerolipid metabolism and a broad spectrum of metabolic pathways

Prenatal Ultrasound and X-ray - Potentially Adverse Effects on the CNS

The aim with this thesis was to assess the impact of prenatal ultrasound exposure on psychotic illness, childhood brain tumors (CBT) and school achievement, and to evaluate prenatal X-ray exposure and the risk of CBT. In a cohort study, children born in Malmö 1973-1978, where prenatal ultrasound was used routinely, were considered exposed (n=13, 212) and children born at hospitals with no use of ultrasound, were considered unexposed (n=357,733). Exposed men had a tendency toward a higher risk of schizophrenia. For other psychoses there were no differences between groups. Other factors related to place of birth might have influenced the results. In a case control study, children born 1975-1984 with a diagnosis of CBT (n=512), and randomly selected control children (n=524) were included. Exposure data on X-ray and ultrasound from antenatal records was completed with information from the Medical Birth Register. We found no overall increased risk for CBT after prenatal X-ray exposure. When stratifying by histological subgroups, primitive neuroectodermal tumors had the highest risk estimates. For ultrasound exposure, no increased risk for CBT was seen and numbers of examinations or gestational age at exposure had no substantial impact on the results. In a follow-up of a randomized trial on prenatal ultrasound scanning 1985-87, we assessed the children’s school grades when graduating from primary school (15-16 years of age). We performed analyses according to randomization, ultrasound exposure in the second trimester and exposure at any time during pregnancy. There were no differences in school performance for boys or girls according to randomization or exposure in the second trimester. Boys exposed to ultrasound any time during fetal life had a reduced mean score in physical education and small, non-significant increased risk of poor school performance in general

Regionalization : a new step in companies internationalization process?

Bakgrund: Det sista steget i Uppsala-skolans etableringskedja innebär att företagen flyttar betydande delar av verksamheten utomlands, men är det verkligen det sista steget? Sedan en tid tillbaka har alltfler företag valt att regionalisera sin internationella verksamhet, vilket innebär att olika nationella verksamheter samordnas och att en regional organisation skapas över nationsgränserna. Hur tar sig en regionalisering i uttryck och kan regionalisering ses som ett nytt steg i företags internationaliseringsprocess? S yfte: Utifrån en studie av företags regionalisering syftar uppsatsen till att bidra med kunskap om företags internationalisering genom att undersöka om regionalisering är ett nytt steg i företags internationaliseringsprocess. Genomförande: För att kunna uppfylla vårt syfte har vi genomfört 12 stycken intervjuer med representanter på åtta multinationella företag som har en regionaliserad Nordenverksamhet. Resultat: Utifrån våra teoretiskt förankrade kriterier för regionalisering har vi kunnat konstatera att samtliga fallföretag kan karaktäriseras som regionaliserade då de; har en geografisk samordning över nationsgränserna genom integration av ländernas verksamhetsområden, har ett gemensamt huvudkontor med en övergripande regionledning, tillämpar både en global och lokal internationaliseringsstrategi, tar vara på kompetenser inom regionen, effektiviserar och rationaliserar sin regionala verksamhet genom att ta hänsyn till var olika verksamhetsfunktioner skall skötas. Vidare har vi kommit fram till att regionalisering kan ses som ett nytt steg i Uppsala-skolans etableringsprocess med utgångspunkt i våra uppsatta kriterier för ett nytt steg. Vi anser således att en regionalisering bidrar med tillräckligt omfattande förändringar av organisationsstrukturen för att det skall kunna klassificeras som ett nytt steg i företags internationaliseringsprocess

Att organisera förskolan. : En kvalitativ undersökning om yttre och inre faktorer som påverkar pedagogers val i den pedagogiska verksamheten.

Sammanfattning Syftet med denna studie var att ta reda på hur yttre och inre faktorer påverkar pedagogens arbete och hur det styrs från huvudmannen ner till förskolan samt hur dessa ramar ger både möjligheter och hinder i den pedagogiska verksamheten. Vi har använt oss av två kvalitativa metoder, intervju och observation, för att få både en uppfattning om hur faktorerna upplevs och hur det faktiskt påverkar pedagogernas val. En fenomenografisk forskningsansats har använts där föresatsen var att få se hur pedagogerna uppfattar sin omgivande miljö. Vi har utfört 9 intervjuer fördelade på tre förskolechefer, tre förskollärare och tre barnskötare. 22 mindre observationer på två förskolor har även utförts. All datainsamling är gjord i samma kommun. Resultatet påvisar att det finns faktorer som påverkar pedagogers val men att det är upp till varje förskola om det blir en förutsättning eller ett hinder. Det skiljer sig mellan förskolor hur de organiserar sig efter organisation, ekonomi, tid, miljö och barngrupp.    Abstract The purpose of this study was to find out how external and internal factors affect the preschool teachers' work and how it is controlled from the principal down to the nursery and how these frames provide both opportunities and obstacles in the educational activities. We have used two qualitative methods, interviews and observation to provide both a sense of how factors are perceived and how it actually affects the preschool teachers' choice. It has used a phenomenographic research approach where the intention was to see how preschool teachers perceive their surrounding environment. We conducted 9 interviews divided with three preschool directors, three preschool teachers and three nannies. It has also been performed 22 minor observations on two preschools. All data collection is made in the same municipality. The result demonstrates that there are factors that affect preschool teachers' choices, but it is up to each preschool if it becomes a condition or an obstruction. It differs from preschools how to organize after the organization, finances, time, environment, and how they divide the children into group

Gynecologists are afraid of prescribing hormone replacement to endometrial/ovarian cancer survivors despite national guidelines-a survey in Sweden

Background: Prolonged survival in ovarian and endometrial cancer patients increases the importance of paying attention to quality of life. Hormone replacement therapy (HRT) after gynecologic cancer has been controversial. With this survey, we sought to describe Swedish gynecologists’ and gynecologic oncologists’ attitudes towards prescribing HRT to these cancer survivors and see if prescribing practice is consistent with the available evidence and national guidelines. Material and methods: A web-based survey containing three hypothetical cases with a total of 15 questions was distributed to gynecologists and gynecologic oncologists in Sweden. Respondents were asked about their HRT prescription practices in endometrial/ovarian cancer patients with moderate to severe menopausal symptoms. Results: In total 262 gynecologists and 24 gynecologic oncologists answered the survey. In the low-risk endometrial cancer case a majority of the gynecologists (55%) and gynecologic oncologists (66.7%) would prescribe local estrogen. A total of 30% of the gynecologists would prescribe estrogen replacement therapy (ERT) in the high-risk endometrial cancer case compared to 58.3% of the gynecologic oncologists. The gynecologic oncologists felt more comfortable treating patients with endometrial cancer than did gynecologists, and the gynecologists were more likely to read the national guidelines. In the ovarian cancer case, 63.7% of the gynecologists would prescribe HRT compared to 92% of the gynecologic oncologists. Conclusion: Swedish gynecologic oncologists have a more favorable attitude towards HRT for endometrial/ovarian cancer patients and feel more comfortable treating their patients than do gynecologists. This study illustrates a need for education in these matters in order not to withhold HRT from women due to doctors’ sometimes unjustified anxiety

Preoperative Fasting and General Anaesthesia Alter the Plasma Proteome

BACKGROUND: Blood plasma collected at time of surgery is an excellent source of patient material for investigations into disease aetiology and for the discovery of novel biomarkers. Previous studies on limited sets of proteins and patients have indicated that pre-operative fasting and anaesthesia can affect protein levels, but this has not been investigated on a larger scale. These effects could produce erroneous results in case-control studies if samples are not carefully matched. METHODS: The proximity extension assay (PEA) was used to characterize 983 unique proteins in a total of 327 patients diagnosed with ovarian cancer and 50 age-matched healthy women. The samples were collected either at time of initial diagnosis or before surgery under general anaesthesia. RESULTS: 421 of the investigated proteins (42.8%) showed statistically significant differences in plasma abundance levels comparing samples collected at time of diagnosis or just before surgery under anaesthesia. CONCLUSIONS: The abundance levels of the plasma proteome in samples collected before incision, i.e., after short-time fasting and under general anaesthesia differs greatly from levels in samples from awake patients. This emphasizes the need for careful matching of the pre-analytical conditions of samples collected from controls to cases at time of surgery in the discovery as well as clinical use of protein biomarkers

Advanced gynaecological cancer : Quality of life one year after diagnosis

Objective: Gynecological cancer treatment impacts women’s physical and psychological health. Our objective was to examine quality of life (QoL) in women with advanced gynecological cancer at diagnosis and one year later, and to identify sociodemographic and clinical characteristics associated with QoL. Methods: Women with endometrial, ovarian or cervical cancer treated in Uppsala, Sweden 2012-2019 were included. FIGO stage ≥II was considered advanced gynecological cancer, whereas women in FIGO stage I were used as a control group. QoL was assessed with SF-36. We obtained information on sociodemographic and clinical characteristics from medical records and health questionnaires. Differences in QoL domains were tested with t-tests, a mixed model ANOVA and multiple linear regression analyses.  Results: The study population (n=372) included 150 (40.3%) women with advanced gynecological cancer. At diagnosis, women with advanced cancer reported lower physical (71.6 vs 81.8 (mean) p<0.05) and role functioning/physical scores (62.6 vs 77.2 (mean) p<0.05) than women in FIGO stage I. One year later, women with advanced cancer reported higher scores in the mental health domain (78.3 vs 73.2 (mean) p<0.05) than women in FIGO stage I. Women with a history of psychiatric illness, higher BMI and comorbidity reported poorer physical and mental QoL at follow-up, while advanced stage, level of education and smoking were not associated with QoL. Conclusion: Women with advanced gynecological cancer have equally good QoL one year after diagnosis as women with limited disease. Women with previous psychiatric illness, high BMI, and comorbidities are at risk of impaired physical and mental health

Advanced gynecological cancer : Quality of life one year after diagnosis

Objective: Gynaecological cancer treatment impacts women's physical and psychological health. Our objective was to examine quality of life (QoL) in women with advanced gynaecological cancer at diagnosis and one year later, and to identify sociodemographic and clinical characteristics associated with QoL. Methods: Women with endometrial, ovarian or cervical cancer treated in Uppsala, Sweden 2012-2019 were included. FIGO stage & GE;II was considered advanced gynaecological cancer, whereas women in FIGO stage I were used as a control group. QoL was assessed with SF-36. We obtained information on sociodemographic and clinical characteristics from medical records and health questionnaires. Differences in QoL domains were tested with t-tests, a mixed model ANOVA and multiple linear regression analyses. Results: The study population (n = 372) included 150 (40.3%) women with advanced gynaecological cancer. At diagnosis, women with advanced cancer reported lower physical (71.6 vs 81.8 (mean) p<0.05) and role functioning/physical scores (62.6 vs 77.2 (mean) p<0.05) than women in FIGO stage I. One year later, women with advanced cancer reported higher scores in the mental health domain (78.3 vs 73.2 (mean) p<0.05) than women in FIGO stage I. However, no difference was found in the QoL scores of women with advanced disease one year after diagnoses when stratified by diagnosis. Women with a history of psychiatric illness and higher BMI reported poorer physical and mental QoL at follow-up, while advanced stage, level of education and smoking were not associated with QoL. Conclusion: Women with advanced gynaecological cancer have equally good QoL one year after diagnosis as women with limited disease. Women with previous psychiatric illness and high BMI, are at risk of impaired physical and mental health