Overexpression of vesicle-associated membrane protein PttVAP27-17 as a tool to improve biomass production and the overall saccharification yields in Populus trees

Background Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth. Results In this study, we report on transgenic hybrid aspen (Populus tremula x tremuloides) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct for Populus tremula x tremuloides vesicle-associated membrane protein (VAMP)-associated protein PttVAP27-17 that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20-44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26-50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control. Conclusions The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants

Pediatric drug safety signal detection: a new drug-event reference set for performance testing of data-mining methods and systems

BACKGROUND: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)-Network of Excellence aims to develop pediatric-specific methods that can be applied to these data sources. A reference set of positive and negative drug-event associations is required. OBJECTIVE: The aim of this study was to develop a pediatric-specific reference set of positive and negative drug-event associations. METHODS: Considering user patterns and expert opinion, 16 drugs that are used in individuals aged 0-18 years were selected and evaluated against 16 events, regarded as important safety outcomes. A cross-table of unique drug-event pairs was created. Each pair was classified as potential positive or negative control based on information from the drug's Summary of Product Characteristics and Micromedex. If both information sources consistently listed the event as an adverse event, the combination was reviewed as potential positive control. If both did not, the combination was evaluated as potential negative control. Further evaluation was based on published literature. RESULTS: Selected drugs include ibuprofen, flucloxacillin, domperidone, methylphenidate, montelukast, quinine, and cyproterone/ethinylestradiol. Selected events include bullous eruption, aplastic anemia, ventricular arrhythmia, sudden death, acute kidney injury, psychosis, and seizure. Altogether, 256 unique combinations were reviewed, yielding 37 positive (17 with evidence from the pediatric population and 20 with evidence from adults only) and 90 negative control pairs, with the remainder being unclassifiable. CONCLUSION: We propose a drug-event reference set that can be used to compare different signal detection methods in the pediatric population

Plant biology through quantitative proteomics

Over the last decade the field of mass spectrometry based proteomics has advanced from qualitative, analyses leading to publications revolving around lists of identified proteins and peptides, to addressing more biologically relevant issues requiring measurement of the abundance of identified proteins and hence quantitive mass spectrometry. The work described in this thesis addresses problems with quantitive proteomics in plant sciences, particularly complications caused by the complexity of plant proteomes (generated by genomic duplications), which makes mass spectrometry-based based proteomic analyses more difficult than in mammalian species. In order to understand complex biological processes it is vital to analyse the participating molecules with as little bias as possible. Strategies for minimizing and maximizing the acquired information in proteomic investigations of plants are presented in the appended papers and discussed in the thesis

Omsorgsfylld landsbygd : Rumsliga perspektiv på åldrande och omsorg på den svenska landsbygden

The aim of this thesis is to study the intersection of rural areas, ageing and care. It is  based on interviews with elderly and caregivers carried out in the municipality of Heby in the middle of Sweden. Care is given a broad definition and includes help with many daily activities given by family members, the public sector, the private sector, voluntary organisations and neighbours. The studied rural area is described as filled with care, as there exist people with care needs and caregivers from several sectors. Together the elderly and their caregivers create a landscape of care which they strive to describe as characterized by mutual dependency and carefulness, as well as created between formal and informal relationships. The different care givers are dependent on, complement and sometimes exclude each other. With an increasing trend with ageing in place, the own home is becoming more Important for the rural aged. This creates special careneeds, and reshapes the home physically and gives it and the local community a specific meaning. The own home and its surroundings are seen as consisting of physical features, social relationships and memories of the lived life. The own home is both seen as a place where the elderly can be independent and as a place where they are dependent, which defines the home as a contradictory place. The study wants to contribute to a more developed theoretical understanding of the rural with an age and care perspective. Above all it is stressed that the rural is filled with care relations. Also it is stated that the elderly live in a constantly changing rural society and that the rural is placed between a material and social understanding respectively between the concepts of periphery and center

Childhood Body Mass Index and Pubertal Timing - Changes over time and associations with adult cardiovascular mortality

Puberty in boys has long been an under-investigated area of research mainly due to the lack of an easily available pubertal marker, corresponding to menarche for girls. Using a unique, large, population-based cohort, this thesis targets some of the knowledge gaps regarding puberty and BMI change during puberty in boys. We collected information on height and weight throughout childhood until young adulthood for all included subjects from archived school health records and from the military conscription register, into the BMI Epidemiology study (BEST) cohort. Using these measurements, we estimated prepubertal childhood BMI, post pubertal young adult BMI, BMI change during puberty, and age at Peak Height Velocity (PHV) an objective assessment of pubertal timing. Through linkage with the Cause of Death register we obtained cause of death for all subjects. Childhood BMI and the prevalence of overweight and obesity among 8-year-old boys have overall increased substantially since birth year 1946 until birth year 2006. However, after a significant increase in BMI starting in the 1970s and with a peak at birth year 1991, we observed a moderate but significant decrease (Paper I). Furthermore, we have demonstrated that childhood BMI was inversely associated with pubertal timing in normal weight but not in overweight boys (Paper II). Age at PHV displayed a clear secular trend towards earlier puberty among boys. Since the 1940s until birth year 1996, the pubertal growth spurt was 1.5 months earlier per decade, and this trend could only slightly be explained by the coinciding increase in childhood BMI (Paper III). We demonstrated that BMI change during puberty, but not childhood BMI, was independently associated with the risk of adult cardiovascular mortality. This association between BMI change during puberty and cardiovascular mortality was non-linear, with 22% increased risk of cardiovascular mortality per additional increase in BMI units for individuals in the highest quartile. (Paper IV). This unique material has enabled us to identify long-term trends of childhood BMI and pubertal timing, and to identify a large BMI increase during puberty as a novel independent risk marker for increased risk of adult cardiovascular mortality. The results from this thesis have the potential to transmit directly into benefits for the society through adjustments of the school health care program for improved identification of individuals at risk

Omsorgsfylld landsbygd : Rumsliga perspektiv på åldrande och omsorg på den svenska landsbygden

The aim of this thesis is to study the intersection of rural areas, ageing and care. It is  based on interviews with elderly and caregivers carried out in the municipality of Heby in the middle of Sweden. Care is given a broad definition and includes help with many daily activities given by family members, the public sector, the private sector, voluntary organisations and neighbours. The studied rural area is described as filled with care, as there exist people with care needs and caregivers from several sectors. Together the elderly and their caregivers create a landscape of care which they strive to describe as characterized by mutual dependency and carefulness, as well as created between formal and informal relationships. The different care givers are dependent on, complement and sometimes exclude each other. With an increasing trend with ageing in place, the own home is becoming more Important for the rural aged. This creates special careneeds, and reshapes the home physically and gives it and the local community a specific meaning. The own home and its surroundings are seen as consisting of physical features, social relationships and memories of the lived life. The own home is both seen as a place where the elderly can be independent and as a place where they are dependent, which defines the home as a contradictory place. The study wants to contribute to a more developed theoretical understanding of the rural with an age and care perspective. Above all it is stressed that the rural is filled with care relations. Also it is stated that the elderly live in a constantly changing rural society and that the rural is placed between a material and social understanding respectively between the concepts of periphery and center

Omsorgsfylld landsbygd : Rumsliga perspektiv på åldrande och omsorg på den svenska landsbygden

The aim of this thesis is to study the intersection of rural areas, ageing and care. It is  based on interviews with elderly and caregivers carried out in the municipality of Heby in the middle of Sweden. Care is given a broad definition and includes help with many daily activities given by family members, the public sector, the private sector, voluntary organisations and neighbours. The studied rural area is described as filled with care, as there exist people with care needs and caregivers from several sectors. Together the elderly and their caregivers create a landscape of care which they strive to describe as characterized by mutual dependency and carefulness, as well as created between formal and informal relationships. The different care givers are dependent on, complement and sometimes exclude each other. With an increasing trend with ageing in place, the own home is becoming more Important for the rural aged. This creates special careneeds, and reshapes the home physically and gives it and the local community a specific meaning. The own home and its surroundings are seen as consisting of physical features, social relationships and memories of the lived life. The own home is both seen as a place where the elderly can be independent and as a place where they are dependent, which defines the home as a contradictory place. The study wants to contribute to a more developed theoretical understanding of the rural with an age and care perspective. Above all it is stressed that the rural is filled with care relations. Also it is stated that the elderly live in a constantly changing rural society and that the rural is placed between a material and social understanding respectively between the concepts of periphery and center

Depreciation and tax deduction regarding RnD-expenses

Avdragsrätten för forsknings- och utvecklingsutgifter, nedan betecknat FoU, är en lex specialis bestämmelse i inkomstskattelagen (1999:1229), vilket framgår av 16 kap. 9 § IL. Det subjekt som hävdar avdrag enligt specialbestämmelsen behöver endast visa att utgiften som erlagts har varit av rimligt intresse sett till verksamheten som bedrivs. Således har FoU-avdraget en vid tillämpning. Periodiseringen sker, för det fall inte annan lag föreskriver annat, enligt det materiella sambandet till redovisningen. Periodiseringen kommer därmed, i viss mån, att påverkas av vilken kompletterande normgivning subjektet tillämpar för redovisningen. Periodiseringen kan dessutom ske enligt skatterättsliga regler, vilket uppsatsen även redogör för.  Eftersom skatterätten har kopplingar till redovisningen är den första delen av uppsatsen fokuserad kring att försöka förklara hur kopplingen är uppbyggd. Begrepp såsom klassificering, god redovisningssed, periodisering, kompletterande normgivning förklaras och problematiseras. Nästkommande avsnitt redogör för tillämpligheten av respektive kompletterande normgivning samt redogör för respektive kompletterande normgivning klassificerar tillgångar. Därefter förklaras mer ingående hur periodiseringen går till utifrån de olika kompletterande normerna samt tillämpliga skatterättsliga regler. I analysen diskuteras vilken påverkan tillämpningen av olika kompletterande normer får för periodiseringsfrågan, hur subjektiviteten hos företag kan leda till skattedriven redovisning, klassificerings- och omfångfrågans betydelse för periodiseringen och konsekvenserna av utformningen av 18 kap. IL. Därtill analyseras skillnaden mellan internt bedriven FoU och externt förvärvad FoU. För de slutsatser som vi drar i vårt arbete hänvisar vi läsaren till avsnitt 7. Analysen och slutsatsen bidrar med insikt om hur olika klassificeringar i redovisningen och beskattningen kan leda till olika utfall

Pubertal timing and adult fracture risk in men: A population-based cohort study

Background: Puberty is a critical period for bone mass accrual, and late puberty in boys is associated with reduced bone mass in adult men. The role of variations in pubertal timing within the normal range for adult fracture risk in men is, however, unknown. We, therefore, assessed the association between age at peak height velocity (PHV), an objective measure of pubertal timing, and fracture risk in adult men. Methods and findings: In the BMI Epidemiology Study Gothenburg, 31,971 Swedish men born between January 1, 1945, and December 31, 1961, with detailed growth data (height and weight) available from centrally archived school healthcare records and the conscription register were followed until December 31, 2016. Age at PHV was calculated according to a modified infancy–childhood–puberty model, and fracture information was retrieved from the Swedish National Patient Register. The mean ± SD age at PHV was 14.1 ± 1.1 years. In total, 5,872 men (18.4%) sustained at least 1 fracture after 20 years of age and 5,731 men (17.9%) sustained a non-vertebral fracture after 20 years of age during a mean ± SD follow-up of 37.3 ± 11.7 years. Cox proportional hazards models adjusted for birth year and country of origin revealed that age at PHV was associated with the risk of any fracture and non-vertebral fracture. Participants with age at PHV in the highest tertile (after 14.5 years of age) were at greater risk of any fracture (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08–1.22, P < 0.001) and non-vertebral fracture (HR 1.16, 95% CI 1.09–1.24, P < 0.001) compared with those with age at PHV in the lowest tertile (at 13.6 years of age or younger). Additional adjustments for birthweight, childhood BMI, adult educational level, and young adult height did not attenuate the associations between age at PHV and adult fracture risk. Limitations of this study include the inability to adjust for important risk factors for fracture, inadequate power to assess the relation between pubertal timing and specific fracture types, and the limited generalizability to other populations. Conclusions: In this study, we observed that late pubertal timing was associated with increased adult fracture risk in men. These findings suggest that information on pubertal timing might aid in the identification of those men at greatest risk of fracture

Rho-kinase inhibitor Y-27632 and hypoxia synergistically enhance chondrocytic phenotype and modify S100 protein profiles in human chondrosarcoma cells

Articular chondrocytes are slowly dividing cells that tend to lose their cell type-specific phenotype and ability to produce structurally and functionally correct cartilage tissue when cultured. Thus, culture conditions, which enhance the maintenance of chondrocyte phenotype would be very useful for cartilage research. Here we show that Rho-kinase inhibition by Y-27632 under hypoxic conditions efficiently maintains and even enhances chondrocyte-specific extracellular matrix production by chondrocytic cells. The effects of long-term Y-27632 exposure to human chondrosarcoma 2/8 cell phenotype maintenance and extracellular matrix production were studied at normoxia and at a 5% low oxygen atmosphere. Y-27632 treatment at normoxia induced ACAN and COL2A1 gene up-regulation and a minor increase of sulfated glycosaminoglycans (sGAGs), while type II collagen expression was not significantly up-regulated. A further increase in expression of ACAN and COL2A1 was achieved with Y-27632 treatment and hypoxia. The production of sGAGs increased by 65.8%, and ELISA analysis revealed a 6-fold up-regulation of type II collagen. Y-27632 also induced the up-regulation of S100-A1 and S100-B proteins and modified the expression of several other S100 protein family members, such as S100-A4, S100-A6, S100-A13 and S100-A16. The up-regulation of S100-A1 and S100-B proteins is suggested to enhance the chondrocytic phenotype of these cells