Mural Cell Associated VEGF Is Required for Organotypic Vessel Formation

Background: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells) and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. Methods and Findings: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. Conclusions: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation

Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Women's access to safe water - In times of change and uncertainty - A case study from Mangapwani in Zanzibar, Tanzania

The main concern of this thesis is to find out how the potable and safe water situation in one village in Zanzibar affects the lives of the women and how the women experience the situation. The focus is on what kinds of constraints there are on a local and administrative level that may affect women’s access to water. The current UN definition of access to water is in its definition an abstract rough measuring of distance and time spent. Research within the field show that access to water is more complicated as there are several constraining factors that affect whether water is accessible or not. On a global level there has been a policy shift within the water sector during the latest decades towards market-based solutions where water is being recognised as an economic good. As an effort to counter balance this process the UN has stated water to be a human right. Still, the neo-liberalisation of water projects in developing countries has led to structures of decentralising water management to the communities, tariff implementation, and cost recovery. Feminist critics have illuminated how, women as an effect of these implementations, have been pushed further to the margins even though they are considered important stakeholders because of their role as water managers in the majority of the developing countries. By examining the women’s situation regarding water in Mangapwani, Zanzibar we try to tie the complicated knots of access to water and the current neo-liberalisation of water policies to a local reality. Mangapwani consists of a poor population who are facing structural changes within the water supply system where an economic view on water is being applied. The women are central in this aspect as they are both responsible for collecting and managing water and hold a vulnerable position in the society. In order to address the purpose of this project a field study has been conducted in Mangapwani, a village area along the western coast of Unguja island in Zanzibar outside Tanzania Mainland. To fulfil the aim a qualitative approach was taken and semi-structured interviews; individual and group interviews, participatory observation and data collection through GPS were carried out. The GPS data analysis was done with GIS (Geographical Information Systems). An important finding of this study is that the water project initiated in Mangapwani that aims to increase the access to water might actually lead to a decrease in access to water because of the low paying capacity of the poorer sections of the population. Another finding is that the current definition of access to water is narrow. With the on-going neo-liberalisation of water management more effort is needed to evaluate how the impacts of water as an economic good will affect poor women’s access to water

Flickor med ADHD : Några lärares erfarenheter och arbetssätt i skolan

Syftet med den här studien är att få ta del av några lärares erfarenhet av att arbeta med flickor som har ADHD, i en pedagogisk kontext. I bakgrunden sker en övergripande genomgång av tidigare forskning och litteratur, som i många fall pekar åt ett och samma håll. Flickor med ADHD upptäcks inte i lika stor utsträckning som pojkar, förmodligen på grund av att de har ett annat beteende och att lärare behöver bli bättre på att se dessa flickor. För att kunna styrka undersökningen tillförlitlighet sker en noggrann redovisning utav metoden som använts i denna studie, vilket innebär att om någon annan skulle göra om samma studie så skulle de komma fram till ett liknande resultat. Den visar också på varför intervjuer är det bästa instrumentet för detta undersökningssyfte. De fem intervjupersoner som valdes antas ha en viss kunskap av flickor med ADHD, då de arbetat med dessa flickor i skolan. Resultatet redovisas uppdelat i tre olika underkategorier där centrala områden belyses med utgångspunkt från frågeställningarna. Den första kategorin handlar om lärarnas kunskap och erfarenheter, den andra om lärarnas arbetssätt och de tredje handlar om hur lärarnas utformning av skolmiljön kan påverka arbetet med dessa flickor. I analysen framkommer det att kunskap om flickors symptombild finns hos berörda lärare, men att de tycker sig ha svårt för att upptäcka dem. Sedan sker en diskussion med för och nackdelar av metoden som använts och av resultatet som framkommit, med förslag till vidare forskning

Flickor med ADHD : Några lärares erfarenheter och arbetssätt i skolan

Syftet med den här studien är att få ta del av några lärares erfarenhet av att arbeta med flickor som har ADHD, i en pedagogisk kontext. I bakgrunden sker en övergripande genomgång av tidigare forskning och litteratur, som i många fall pekar åt ett och samma håll. Flickor med ADHD upptäcks inte i lika stor utsträckning som pojkar, förmodligen på grund av att de har ett annat beteende och att lärare behöver bli bättre på att se dessa flickor. För att kunna styrka undersökningen tillförlitlighet sker en noggrann redovisning utav metoden som använts i denna studie, vilket innebär att om någon annan skulle göra om samma studie så skulle de komma fram till ett liknande resultat. Den visar också på varför intervjuer är det bästa instrumentet för detta undersökningssyfte. De fem intervjupersoner som valdes antas ha en viss kunskap av flickor med ADHD, då de arbetat med dessa flickor i skolan. Resultatet redovisas uppdelat i tre olika underkategorier där centrala områden belyses med utgångspunkt från frågeställningarna. Den första kategorin handlar om lärarnas kunskap och erfarenheter, den andra om lärarnas arbetssätt och de tredje handlar om hur lärarnas utformning av skolmiljön kan påverka arbetet med dessa flickor. I analysen framkommer det att kunskap om flickors symptombild finns hos berörda lärare, men att de tycker sig ha svårt för att upptäcka dem. Sedan sker en diskussion med för och nackdelar av metoden som använts och av resultatet som framkommit, med förslag till vidare forskning

Youth and stress : a study of stress and psychosomatic symptoms among secondary school students

BAKGRUND: Stress och psykosomatiska besvär är ett av de allvarligaste folkhälsoproblemen i Sverige. Psykisk ohälsa omfattar cirka 20% av sjukdomsbördan i Sverige. Även ungdomar uppvisar ökad grad av stress och psykosomatiska besvär. SYFTE: Syftet med studien var att undersöka förekomsten av självupplevd stress och psykosomatiska besvär hos gymnasieelever på en svensk gymnasieskola. MATERIAL OCH METOD: En enkät delades ut på skolan. 970 elever besvarade enkäten (75%). Enkäten innehöll 16 frågor rörande självupplevd stress och psykosomatiska besvär. Bakgrundsvariabler var kön, årskurs och program. RESULTAT: Majoriteten av eleverna känner sig ofta glada, att de klarar det de vill och har en positiv framtidstro, men en hög andel av eleverna upplever ofta stress, framför allt skolstress. Psykosomatiska besvär i form av sömnsvårigheter, oro, irritation, och nedstämdhet är vanliga. Det finns en tydlig könsskillnad i resultaten. Flickorna har en högre grad av stress och psykosomatiska besvär och en lägre grad av glädje, bemästring och framtidstro. De flesta eleverna hade en vuxen att prata med och i nio fall av tio var det en förälder. De som inte hade någon sådan vuxen uppvisade dubbelt så hög andel psykosomatiska besvär. SLUTSATSER OCH REKOMMENDATIONER: Studien visade att det finns ett samband mellan stress och psykosomatiska besvär. Det är viktigt att skolan, både lokalt och nationellt, vidtar åtgärder för att minska skolstressen. Samhället bör öka sitt stöd till familjer, så att fler ungdomar kan ha en öppen och förtroendefull relation till sina föräldrar. Det krävs vidare forskning om flickornas höga andel av stress och psykosomatiska besvär, så att trenden med ökade ohälsotal för kvinnor kan brytas.BACKGROUND: Stress and psychosomatic symptoms is one of the major public health problems in Sweden. Psychological disease accounts for 20% of the burden of disease in Sweden. Also young people show an increasing degree of stress and psychosomatic symptoms. OBJECTIVES: The objective of the study was to investigate the prevalence of self-rated stress and psychosomatic symptoms among secondary school students. MATERIAL AND METHODS: A questionnaire was distributed. 970 students filled it out (75%). The questionnaire had 16 questions on self-rated stress and psychosomatic symptoms. The background variables were sex, grade and program. RESULTS: The majority of the students often felt happy, a sense of mastering and had a positive view of their future, but a high proportion of the students felt stress, the level of school related stress was very high. Psychosomatic symptoms such as problems with sleep, feeling anxious, irritable and low was common. There was a clear gender difference. The girls had a higher degree of stress and psychosomatic symptoms and lower degree of happiness, sense of mastering and positive view of their future. A majority of the students had an adult to talk to, which in 90% of the cases was a parent. Those students who didn’t have such an adult had twice as high degree of psychosomatic symptoms. CONCLUSIONS AND RECOMMENDATIONS: The study showed an association between stress and psychosomatic symptoms. It is important that the school, both on local and national level, take measures to decrease the level of school related stress. The society should increase its support to families, so more young people can have an open and trusting relationship to their parents. Further research is needed about the high level of stress and psychosomatic symptoms among girls, so the increasing burden of disease among women can be reversed.ISBN 91-7997-133-4</p

New Techniques for Chiral Separations

Gas chromatography (GC) has been utilized for the study of enantiomer resolution of the atropisomers of PCBs, o,p´-DDD and o,p´-DDT. Different substituents and concentrations of cyclodextrin, capillary dimensions and type of stationary phase films have been investigated to achieve the resolution of as many of the atropisomers on one column as possible. The results indicated that the butyl substitution of 6-hydroxyl and the methyl substitution of 2- and 3-hydroxyl were the most promising for the enantiomeric separation. Using Capillary Electrophoresis (CE), the trimers and monomers of PM-β-CDs were compared for enantiomeric resolution, as well as comparing the cationic PMMA-β-CD with the anionic HS-β-CD. In these studies the trimer did not show an improved resolution for mepivacaine, when compared to the equimolar concentration of the monomer. The cationic CD gave increased resolution values for ibuprofen when compared to the anionic CD. A scheme for reversing enantiomeric elution order of both the basic propranolol and acidic ibuprofen is also presented, with the aim of facilitating the detection of impurities in a high sample loading. The detection of 1% of each enantiomer of propranolol, and 1% of R(-)-ibuprofen, was demonstrated, with elution prior to the tailing peak of the corresponding enantiomer. Dimethylacrylamide-coated capillaries were used in this work, and the stability of this coating was demonstrated, giving a highly reduced electroosmotic flow for up to six months. Enantiomeric baseline separations of omeprazole and 5-hydroxyomeprazole have also been achieved with both CE and Open Tubular Capillary Electrochromatography (OT-CEC) methods. With CE-UV, both a non-aqueous method (using HDMS-β-CD) and an aqueous method (using HS-β-CD) were used for enantiomeric resolution of the two racemates. Resolution of omeprazole was also achieved using CE-Electrospray Ionization-Mass Spectrometry (ESI-MS). In OT-CEC, avidin was immobilized on the inside surface of a fused silica capillary and was employed as chiral selector for the enantiomeric baseline resolution of omeprazole and 5-hydroxyomeprazole