Functional characterization of hexokinases in the moss Physcomitrella patens

Carbohydrates are important nutrients and structural components in all living organisms. In plants they affect the developmental and metabolic processes throughout the plant life cycle. However, the mechanisms by which plants recognise and respond to carbohydrates are mainly unknown. Hexokinase, an enzyme that mediates the first catalytic step in hexose metabolism, has recently been suggested to be involved in sugar sensing and signalling in plants. The moss Physcomitrella patens has recently emerged as a powerful model system in plant functional genomics following the discovery that gene targeting works in it with frequencies comparable to those in yeast. The aim of this thesis was to learn more about the function of plant hexokinases, both as key metabolic enzymes and in their putative role as sensors in sugar signalling, using Physcomitrella patens as a model system. Five hexokinases from Physcomitrella patens were cloned and studied with respect to their subcellular localizations. PpHxk1 and PpHxk5 are located in the stroma of chloroplasts and are dependent on N-terminal transit peptides for correct localization. PpHxk2 and PpHxk3 both contain hydrophobic membrane anchors that localize the proteins to the outer envelope of chloroplasts. PpHxk4 contain neither a transit peptide nor an anchor, and is found in the cytosol. A targeted knockout revealed that PpHxk1 is the major hexokinase in Physcomitrella, accounting for 80% of the glucose phosphorylating activity. Consistent with this, the knockout mutant exhibits an artificial starvation phenotype with altered sensitivities to plant hormones and a disturbed development

Pathways to Employment

Background This project’s aims are twofold (1) to uncover and define the underlying theories of change guiding competing active labor market programs (ALMP) in Sweden, and (2) to assess the relative effectiveness of these competing programs in a theory-based non-randomized controlled trial. The purpose is to assess the extent to which competing ALMPs are effective in moving long-term unemployed individuals (i.e. unemployed for 6 months or more) closer to the labor-market. Methods/Design This project will engage ALMP program administrators and service providers in semi-structured interviews. The transcribed interview material will be used as a basis for program theory reconstruction. All specified program theories will be presented back to program stakeholders for validation. ALMP program effectiveness will be assessed quasi-experimentally with pre- (T1) and posttest (T2) collection of self-reported data. Additionally, official register data from the Longitudinal integrated database for health insurance and labor market studies (LISA) will be collected for all participants. In addition, a matched sample will be collected from LISA to be used as a non-treated control group on final policy outcomes (e.g., employment, salary/wage). This study also assesses program implementation and economic outcomes of the included ALMPs. Discussion Long-term unemployment has profound impact of the health and wellbeing of individuals, families, and communities. In addition, the effects of long-term unemployment have been found to impact subgroups differently. Today we have scant knowledge on the mechanisms that are influential in moving individuals from long-term unemployment closer to the labor market. This study is designed to answer six research questions using a variety of methods (mixed-methods) and outcome measures (self-report, official register). In addition, this study leverages official register data to construct an untreated control group. This study will assess the extent to which an emerging theory of becoming job ready holds under experimental scrutiny

Omvårdnadsåtgärder kring måltiden som främjar hälsan för personer med anorexia nervosa. En litteraturstudie.

Bakgrund: Anorexia nervosa är en psykisk sjukdom som påverkar både den fysiska och psykiska hälsan och minst 10% av patientgruppen dör i sjukdomen på lång sikt. Måltiden är en viktig del av behandlingen inom slutenvården och sjuksköterskan har en viktig roll i att hjälpa patienterna mot en god hälsa. Syfte: Syftet med litteraturstudien var att beskriva vilka omvårdnadsåtgärder i anslutning till måltiden som kan främja hälsan för personer med anorexia nervosa inom slutenvården. Resultat: En god terapeutisk relation är en förutsättning för att normalisera ätbeteendet hos patienterna. Tydliga rutiner är viktiga för att återfå ett normalt ätmönster och främja hälsan. Under måltiden bör sjuksköterskan sitta med för att handleda, agera förebild och använda olika metoder för att distrahera patienten, såsom musik och videoklipp. När patienterna får agera förebild för varandra kan deras utveckling i behandlingen bli positivt påverkad. Diskussion: Litteraturstudien har en mindre omfattning. Eftersom en större litteraturstudie aldrig gjorts på ämnet skulle en sådan behövas för att sammanställa kunskap som kan vara användbar i den kliniska sjuksköterskan arbete

Two novel types of hexokinases in the moss Physcomitrella patens

<p>Abstract</p> <p>Background</p> <p>Hexokinase catalyzes the phosphorylation of glucose and fructose, but it is also involved in sugar sensing in both fungi and plants. We have previously described two types of hexokinases in the moss <it>Physcomitrella</it>. Type A, exemplified by PpHxk1, the major hexokinase in <it>Physcomitrella</it>, is a soluble protein that localizes to the chloroplast stroma. Type B, exemplified by PpHxk2, has an N-terminal membrane anchor. Both types are found also in vascular plants, and localize to the chloroplast stroma and mitochondrial membranes, respectively.</p> <p>Results</p> <p>We have now characterized all 11 hexokinase encoding genes in <it>Physcomitrella</it>. Based on their N-terminal sequences and intracellular localizations, three of the encoded proteins are type A hexokinases and four are type B hexokinases. One of the type B hexokinases has a splice variant without a membrane anchor, that localizes to the cytosol and the nucleus. However, we also found two new types of hexokinases with no obvious orthologs in vascular plants. Type C, encoded by a single gene, has neither transit peptide nor membrane anchor, and is found in the cytosol and in the nucleus. Type D hexokinases, encoded by three genes, have membrane anchors and localize to mitochondrial membranes, but their sequences differ from those of the type B hexokinases. Interestingly, all moss hexokinases are more similar to each other in overall sequence than to hexokinases from other plants, even though characteristic sequence motifs such as the membrane anchor of the type B hexokinases are highly conserved between moss and vascular plants, indicating a common origin for hexokinases of the same type.</p> <p>Conclusions</p> <p>We conclude that the hexokinase gene family is more diverse in <it>Physcomitrella</it>, encoding two additional types of hexokinases that are absent in vascular plants. In particular, the presence of a cytosolic and nuclear hexokinase (type C) sets <it>Physcomitrella </it>apart from vascular plants, and instead resembles yeast, where all hexokinases localize to the cytosol. The fact that all moss hexokinases are more similar to each other than to hexokinases from vascular plants, even though both type A and type B hexokinases are present in all plants, further suggests that the hexokinase gene family in <it>Physcomitrella </it>has undergone concerted evolution.</p

Alternativa distributionskanaler för mjölkprodukter

Mjölkproduktion är viktigt för svenskt jordbruk. Sektorn står för sammanlagt en femtedel av jordbrukets produktionsvärde. Trenden bland mjölkproducenterna går mot att de med små besättningar avvecklar sin verksamhet medan de stora växer. Orsaken till det konstant minskande antalet producenter är rationaliseringen inom jordbruket, men även den svaga lönsamheten som i dagsläget råder i branschen. Distributionen och förädlingen inom den svenska mjölkindustrin domineras av ett fåtal stora mejerikooperativ som har marknadsmakt. Genom att använda sig av alternativa distributionskanaler, som i denna uppsats definieras som de kanaler som inte är direkt via de stora konventionella mejerikooperativen så som Arla, Milko och Skånemejerier, kan mjölkproducenten få större inflytande i distributionskedjan. Denna typ av distribution kan även skapa mervärden för producenten vilket gör att motiven att behålla verksamheten ökar. Problemet för mjölkproducenter som vill distribuera sina produkter via alternativa kanaler är att det är svårt för nya aktörer att träda in på mjölkmarknaden på grund av marknadsdominansen. Syftet med denna uppsats är att studera vilka fördelar och problem mjölkproducenter upplever med att använda alternativa distributionskanaler. Syftet är även att analysera vilka strategier mjölkproducenterna kan utnyttja för att vara konkurrenskraftiga på marknaden när de använder sig av alternativa distributionskanaler. För att utreda uppsatsens syfte har en empirisk studie i form av en kvalitativ intervjustudie med mjölkproducenter som använder alternativa distributionskanaler gjorts. Intervjustudien har kompletterats med en litteraturstudie inom området. Resultatet är att de fördelar mjölkproducenterna upplever med de alternativa distributions-kanalerna är att de får ökat inflytande och kontroll i distributionskanalen. En annan betydande fördel är att de kan skapa ett eget varumärke baserat på mervärden och därigenom förmedla en stolthet över sin produktion. Problem för mjölkproducenter som använder sig av alternativa distributionskanaler är att mejeriindustrin är reglerad av hårda krav och dessutom är kapitalintensiv. Ett annat problem är att distributionen blir ineffektiv då mjölkproducenten i många fall är småskalig och inte kan utnyttja stordriftsfördelar. Mjölkproducenterna upplever även svårigheter i att komma in i butikssortimentet. Ett framtida problem på marknaden för mjölkprodukter som distribueras genom alternativa kanaler är att konkurrensen ökar. För att en mjölkproducent ska kunna använda alternativa distributionskanaler och samtidigt vara konkurrenskraftig på marknaden krävs att producenten har en strategi som bygger på ett koncept med ett varumärke som förmedlar produktens mervärden. Dessa mervärden måste producenten sedan förmedla till konsumenten på ett trovärdigt sätt för att kunna bygga upp ett konkurrenskraftigt varumärke. Distributionen bör ske med få mellanhänder så att producenten har kontroll och inflytande över kedjan. För att underlätta och effektivisera distributionen bör producenten samarbeta med andra aktörer som strävar mot gemensamma intressen. Distributionen av mjölkprodukter bör ske genom en intensiv strategi men profileras med en exklusiv image eller så bör mjölken vidareförädlas så att produkten blir mer unik. På vilket sätt en mjölkproducent bör utnyttja distributionsstrategierna beror på verksamhetens omfattning och struktur

The role of relationships in lending to farmers

There have been significant changes in the agricultural sector during the past 20 years (Jordbruksverket, 2008). The development of today is towards deregulation and adaption to global market conditions. As farmers try to adapt to the changed and more competitive market conditions investments are often necessary (LRF Konsult et al, 2012). Loans to agriculture and forestry businesses have increased to record levels and debt has doubled over the past years. The financial turbulence of the past years has contributed to an increase of the meaningfulness and willingness of the banks to be able to understand and handle risks associated with agriculture and forestry (Breiding, 2010). Handelsbanken has during the last five years made a major expansion in the segment of farm and forestry clients. When assessing finance to farm businesses, it can be a costly and complicated process for the loan officer to find the right objective information; therefore the personal contact and relationship between the loan officer and the credit applicant is a very important factor in the credit evaluation process (Akhavein et al, 2004). Yet little is known about how the relationship is established and which factors affect the relationship (Hedelin & Sjöberg, 1992; Bruns 2003). The farm- and forestry division of Handelsbanken is interested in investigating how the relationship between the bank and its clients is established and what factors are influencing the relationship. The purpose of this study is to investigate how loan officers establish an understanding of applicants' personal character in the loan application process, and how that understanding together with the personal relationship that is formed between the loan officer and the credit applicant affects the credit evaluation. The approach of this project is explorative. According to Kvale (1997) the aim of an explorative study is to search for new dimensions of the unit of analysis. The reason for choosing an explorative approach of the study is that there has not been much research about the lending relationship between loan officers and farmers (Lindstrand, 2003). This study consists of a theoretical framework where data was collected in order to obtain a general understanding about relationships and the problems and solutions associated with lending relationships. In order to obtain a deeper understanding of the characteristics of the relationship in the credit evaluation process, literature that describes the problem associated with lending relationships is studied. A case study including interviews with 16 loan officers working at Handelsbanken were conducted in March and April 2012, in order to collect data for studying the relationship between loan officers and farmers. The conclusion that can be drawn from this study is that the loan officers establish an understanding of applicants' personal character in the loan application process by being interested in the credit applicant and his business. This creates legitimacy for the loan officer and he receives the credit applicants’ approval, which creates trust in the relationship. A relationship built on trust leads to improved communication between the loan officer and the credit applicant. The good communication can increase the flow of information, which leads to the establishment of a mutual understanding. This understanding between the parties decreases the problems of information asymmetry in the credit evaluation process, which makes the process more efficient and viable in a long-term perspective.Under de senaste 20 åren har det skett stora förändringar inom den agrara sektorn i Sverige (Jordbruksverket, 2008). Förändringarna har inneburit avregleringar av jordbrukspolitiken, vilket resulterat i lantbruksföretagare måste anpassa sig till alltmer marknadsmässiga krav och regelverk. Många lantbruksföretagare måste göra stora investeringar för att uppfylla de nya kraven och vara konkurrenskraftiga på marknaden (LRF Konsult et al, 2012). Investeringar innebär för många lantbrukare belåning av externt kapital, vilket också märks hos banker och kreditinstitut där utlåningsnivåerna till kunder inom den agrara sektorn fördubblats under de senaste åren. Den finansiella turbulens som råder på världsmarknaden sedan en tid gör att det är än viktigare att bankerna är insatta i och förstår förutsättningarna och riskerna med att bedriva skog- och lantbruk (Breiding, 2010). Handelsbanken är en av de svenska bankerna som under de senaste åren gjort en stor satsning inom detta segment genom att bygga upp en egen division för skog och lantbruk. Det kan vara en kostsam och komplicerad process för bankerna att hitta trovärdig och objektiv information om lantbruksföretag (Akhavein et al, 2004). Den personliga relationen mellan kreditgivaren och kredittagaren kan därför vara av stor betydelse för att kunna göra en rättvis kreditbedömning. Det finns inte så mycket forskning gjord om vilken betydelse den personliga relationen har vid kreditbedömningar och vilka faktorer som påverkar relationen (Hedelin & Sjöberg, 1992; Bruns 2003). Handelsbanken skog- och lantbruk är intresserade av att få en djupare förståelse för hur relationen mellan kreditgivare och kredittagare etableras samt hur relationen påverkar kreditgivningsprocessen. Syftet med denna studie är att undersöka hur kreditgivare skapar sig en förståelse för kredittagarens personliga egenskaper, samt hur denna förståelse påverkar kreditbedömningsprocessen. Denna studie har ett explorativt angreppssätt. Enligt Kvale (1997) är syftet med en explorativ studie att söka efter nya dimensioner av studieobjektet. Ett explorativt angreppssätt passar denna studie eftersom ämnet ”betydelsen av relationen mellan kreditgivare och lantbruksföretagare” är relativt outforskat (Lindstrand, 2003). Denna studie består av ett teoretiskt ramverk för att ge en förståelse om affärsrelationer. Litteraturstudien består av en genomgång av vetenskapliga artiklar och böcker för att ge en djupare inblick i bankrelationer och relationens betydelse i kreditgivningsprocessen. För att applicera frågeställningen på lantbrukssektorn gjordes under mars och april 2012 en telefonintervjustudie med 16 skog- och lantbruksansvariga kredithandläggare inom Handelsbanken. Slutsatsen av denna studie är att kreditgivaren skapar sig en förståelse för kredittagarens personliga egenskaper genom sitt intresse för kredittagaren och dennes verksamhet. Kreditgivarens intresse och förståelse skapar ett gillande hos kredittagaren, vilket resulterar i ökad legitimitet för kreditgivaren och skapar ett förtroende i relationen. En relation baserad på förtroende leder till förbättrad kommunikation mellan parterna. Förbättrad kommunikation mellan de båda parterna kan öka flödet av information i kreditbedömningsprocessen. Ökat flöde av information och en ömsesidig förståelse minskar problemen med asymmetrisk information. Detta resulterar i en effektivare kreditbedömningsprocess och ger bättre förutsättningar för att relationen ska vara hållbar i ett längre perspektiv

Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.

AIMS/HYPOTHESIS: To date, the molecular function of most of the reported type 2 diabetes-associated loci remains unknown. The introduction or removal of cytosine-phosphate-guanine (CpG) dinucleotides, which are possible sites of DNA methylation, has been suggested as a potential mechanism through which single-nucleotide polymorphisms (SNPs) can affect gene function via epigenetics. The aim of this study was to examine if any of 40 SNPs previously associated with type 2 diabetes introduce or remove a CpG site and if these CpG-SNPs are associated with differential DNA methylation in pancreatic islets of 84 human donors. METHODS: DNA methylation was analysed using pyrosequencing. RESULTS: We found that 19 of 40 (48%) type 2 diabetes-associated SNPs introduce or remove a CpG site. Successful DNA methylation data were generated for 16 of these 19 CpG-SNP loci, representing the candidate genes TCF7L2, KCNQ1, PPARG, HHEX, CDKN2A, SLC30A8, DUSP9, CDKAL1, ADCY5, SRR, WFS1, IRS1, DUSP8, HMGA2, TSPAN8 and CHCHD9. All analysed CpG-SNPs were associated with differential DNA methylation of the CpG-SNP site in human islets. Moreover, six CpG-SNPs, representing TCF7L2, KCNQ1, CDKN2A, ADCY5, WFS1 and HMGA2, were also associated with DNA methylation of surrounding CpG sites. Some of the type 2 diabetes CpG-SNP sites that exhibit differential DNA methylation were further associated with gene expression, alternative splicing events determined by splice index, and hormone secretion in the human islets. The 19 type 2 diabetes-associated CpG-SNPs are in strong linkage disequilibrium (r (2) > 0.8) with a total of 295 SNPs, including 91 CpG-SNPs. CONCLUSIONS/INTERPRETATION: Our results suggest that the introduction or removal of a CpG site may be a molecular mechanism through which some of the type 2 diabetes SNPs affect gene function via differential DNA methylation and consequently contributes to the phenotype of the disease

Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people

Objective To investigate whether sleep deprived people are perceived as less healthy, less attractive, and more tired than after a normal night’s sleep

Two common genetic variants near nuclear-encoded OXPHOS genes are associated with insulin secretion in vivo

Context Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the β-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes. OBJECTIVE: The aim of this study was to identify genetic loci in or adjacent to nuclear encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo. DESIGN AND METHODS: To find polymorphisms associated with glucose-stimulated insulin secretion, data from a genome-wide association study (GWAS) of 1467 non-diabetic individuals, the Diabetes Genetic Initiative (DGI), was examined. 413 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) ≥0.05 located in or adjacent to 76 OXPHOS genes were included in the DGI GWAS. A more extensive population based study of 4323 non-diabetics, the PPP-Botnia, was used as a replication cohort. Insulinogenic index during an oral glucose tolerance test (OGTT) was used as a surrogate marker of glucose-stimulated insulin secretion. Multivariate linear regression analyses were used to test genotype-phenotype associations. RESULTS: Two common variants were indentified in the DGI, where the major C-allele of rs606164, adjacent to NDUFC2 (NADH dehyrogenase (ubiqinone) 1 subunit C2), and the minor G-allele of rs1323070, adjacent to COX7A2 (cythochrome c oxidase subunit VIIa polypeptide 2), showed nominal associations with decreased glucose-stimulated insulin secretion (p=0.0009 respective p=0.003). These associations were replicated in PPP-Botnia (p=0.002 and p=0.05). CONCLUSION: Our study shows that genetic variation near genes involved in oxidative phosphorylation may influence glucose-stimulated insulin secretion in vivo

Neighborhood conditions in a Swedish context-Two studies of reliability and validity of virtual systematic social observation using Google Street View

IntroductionThe goal of these studies was to investigate the reliability and validity of virtual systematic social observation (virtual SSO) using Google Street View in a Swedish neighborhood context.MethodsThis was accomplished in two studies. Study 1 focused on interrater reliability and construct validity, comparing ratings conducted in-person to those done using Google Street View, across 24 study sites within four postal code areas. Study 2 focused on criterion validity of virtual SSO in terms of neighborhoods with low versus high income levels, including 133 study sites within 22 postal code areas in a large Swedish city. In both studies, assessment of the neighborhood context was conducted at each study site, using a protocol adapted to a Swedish context.ResultsScales for Physical Decay, Neighborhood Dangerousness, and Physical Disorder were found to be reliable, with adequate interrater reliability, high consistency across methods, and high internal consistency. In Study 2, significantly higher levels of observed Physical Decay, Neighborhood Dangerousness, and signs of garbage or litter were observed in postal codes areas (site data was aggregated to postal code level) with lower as compared to higher income levels.DiscussionWe concluded that the scales within the virtual SSO with Google Street View protocol that were developed in this series of studies represents a reliable and valid measure of several key neighborhood contextual features. Implications for understanding the complex person-context interactions central to many theories of positive development among youth were discussed in relation to the study findings