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Many decisions within healthcare are based on results from laboratory tests. These results all have an uncertainty, which can be either neglectable or large enough to affect the clinical assessment. In external quality assessment (EQA) the laboratories make independent observations on the same control sample, with values unknown for the participants. The results can be used to determine if quality improvement is needed. We present EQA data for laboratory tests with three different measurement scales; quantitative, ordinal and nominal. Results from EQA should be used in the discussions of quality in test results and necessary analytical performance specifications should be agreed upon.

The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity., National Science Foundation (U.S.). (Grant PHY1743900), National Institutes of Health (U.S.) (Grants GM123511, GM117370 and T32CA009172), German Research Foundation Research Fellowship (DE 3069/1-1)

Denna rapport redogör för ett projekt inom området industriell teknik och hållbarhet. Studien utreder möjligheten att tillämpa en förnyelsebar energikälla där solenergi skall utvinnas genom solceller. Energin som utvinns skall till en viss grad leda till energiförsörjning hos Rosendals Trädgård. Verksamhet har valts som ett hypotetiskt förslag på hur man kan anpassa, beräkna och implementera solceller. För att uppnå ett realistiskt förslag har företaget HP Solartech används som ett “verktyg” och teoretiskt stöd kring solcellstekniker och beräkningsmodeller. Syftet med detta projekt var att ta fram beslutsunderlag för Rosendal, med hjälp av att använda HP Solartechs simuleringsprogram för solcellsanläggningar. Resultatet visade att en solcellsanläggning på Rosendal skulle täcka 24% av den årliga energiförbrukningen och ge en kostnadsbesparing på SEK 160 900. This report describes a project concerning the area within industrial technology and sustainability. The research investigates the possibility to apply a renewable energy source utilizing solar energy through solar cells. The energy that extracts shall, to a certain extent, be applied as an energy source to the establishment Rosendals Trädgård. Rosendals Trädgård was chosen as a hypothetical example of how an implementation of an organization can be successful. The company HP solartech was a leading hand during the study since they attain professional knowledge within this subject. In order to make the study accurate, HP solartech supported the data by sharing the ground theories about solar energy, the difficult calculations and the implementation of solar cells. With their guiding and support, valuable facts and results was attained. The aim to this project is to present a proposition to Rosendals Trädgråd with support from HP solartech. The result for Rosendal turned out to a production of solar energy that covers 24% of their current energy consumption and an economical saving of SEK 160 900 annually.

© 2019 Elsevier Inc. Enhancers are DNA elements that are bound by transcription factors (TFs), which recruit coactivators and the transcriptional machinery to genes. Phase-separated condensates of TFs and coactivators have been implicated in assembling the transcription machinery at particular enhancers, yet the role of DNA sequence in this process has not been explored. We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactivators. A combination of specific structured (TF-DNA) and weak multivalent (TF-coactivator) interactions allows for condensates to form at particular genomic loci determined by the DNA sequence and the complement of expressed TFs. DNA features found to drive condensation promote enhancer activity and transcription in cells. Our study provides a framework to understand how the genome can scaffold transcriptional condensates at specific loci and how the universal phenomenon of phase separation might regulate this process. Shrinivas et al. demonstrate that specific types of motif compositions encoded in DNA drive localized formation of transcriptional condensates. These findings explain how phase separation can occur at specific genomic locations and shed light on why only some genomic loci become highly active enhancers.

3131 Background: The molecules of the cell are compartmentalized into membrane- and non-membrane-bound organelles. Many non-membrane-bound organelles are phase-separated biomolecular condensates with distinct physicochemical properties that can absorb and concentrate specific proteins and nucleic acids involved in discrete biochemical processes. We reasoned that selective condensate partitioning might also occur with small molecule drugs whose targets occur within condensates, and that the therapeutic index and efficacy of such compounds might therefore relate to their ability to partition into condensates. Methods: To study the behavior of drugs within condensates, these were modeled in cells and in vitro with purified proteins and visualized by fluorescent confocal microscopy. The functional outcomes of condensate partitioning were queried in cells. Results: We found that cisplatin, tamoxifen, JQ1, THZ1, and mitoxantrone are concentrated in specific protein condensates in vitro, and that this occurs through physicochemical properties independent of the drug target. A screen of a chemically diverse fluorescent probes and mutant-protein condensates demonstrated that pi-system interactions between aromatic moieties in the protein and small molecule govern concentration in condensates. These results show that clinically important drugs partition into specific protein condensates in vitro by virtue of defined chemical properties, thereby altering their local concentration. In vitro droplet assays revealed that cisplatin is selectively concentrated in transcriptional condensates, and that this ability is required for efficient platination of target DNA. In cell studies revealed that cisplatin preferentially targets DNA contained within MED1 condensates, and disrupts the genetic regulatory elements that compose phase-separated transcriptional condensates. Live cell imaging demonstrated that transcriptional condensates are dissolved by cisplatin, whereas other condensates remain intact. Conclusions: Our results show that antineoplastic drugs partition selectively into biomolecular condensates, that this can occur through physicochemical properties independent of their molecular targets, and that drug activity may occur through condensate-related mechanisms. These results have implications for development of efficacious cancer therapeutics; effective target engagement will depend on factors such as drug partitioning in condensates. Assays of the type described here may thus help optimize condensate partitioning, target engagement, and the therapeutic index of drugs for cancer treatment.

SummaryWound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogendeficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.Supplementary Material to this article is available online at www.thrombosis-online.com.

The synthesis of pre-mRNA by RNA polymerase II (Pol II) involves the formation of a transcription initiation complex, and a transition to an elongation complex

Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well characterized, but little is known about the mechanisms by which ADs effect gene activation. Here, we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation., National Institutes of Health (U.S.) (Grant GM123511), National Institutes of Health (U.S.) (Grant GM117370), Swedish Research Council (Postdoctoral Fellowship VR 2017-00372), Damon Runyon Cancer Research Foundation ( Fellowship 2309-17)

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in the control of key cell-identity genes., National Institutes of Health (U.S.) (Grant GM123511), National Institutes of Health (U.S.) (Grant P01-CA042063), National Science Foundation (U.S.) (Grant PHY-1743900), National Cancer Institute (U.S.) (Grant P30-CA14051)

Studien fokuserar på om könsfördelningen i företagsledningen hos svenska börsnoterade företag påverkar den frivilliga information som redovisas i årsredovisningar. Data har samlats in från databaser och manuellt från årsredovisningar. Studien använder en regressionsanalys och resultatet visar att fler kvinnor i styrelsen eller en kvinnlig ekonomidirektör leder till att företag redovisar mer frivillig information. Vi finner inget samband mellan könet hos den verkställande direktören och frivillig redovisning, något som förmodligen beror på att urvalet endast består av två procent kvinnliga verkställande direktörer. Resultatet bidrar till att öka informationen om frivillig redovisning och hur det påverkas av könsfördelning i svenska företagsledningar. Det är av praktisk relevans för svenska företag och investerare då ökad informationsgivning bidrar till minskad informationsasymmetri vilket ger lägre agent- och kapitalkostnader. Framtida studier kan med fördel använda ett större urval för att undersöka om könsfördelningen i ledningen påverkar mängden frivillig redovisning. Exempelvis genom att även inkludera mindre och onoterade företag.

In order for a new organism to form, the genomes of the highly specialized egg and sperm need to be reprogrammed into a totipotent state that is capable of generating all of the cell types that comprise an organism. This reprogramming occurs by erasing chromatin modifications, leaving the cells in a naive state, followed by the induction of specialized programming events. Pioneer factors bind to the genome prior to zygotic genome activation, followed by acetylation of histones and further chromatin specialization by the addition of methylation marks later during differentiation. Genome-wide approaches have provided insight into the genomic and epigenomic regulation of gene expression during development, providing a new perspective on the process of cell specification and differentiation. In this review, we discuss how distal DNA and core promoter elements, RNA polymerase pausing, transcription factors, and co-regulators interact to shape the chromatin landscape and direct tissue-specific expression patterns during embryo development, focusing on the well-characterized Drosophila embryo.

Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro’s critical role in development and disease, relatively little is known about Atro’s binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways. We show that Atro regulates Dpp and Notch signaling in larval imaginal discs, at least partially via regulation of thickveins and fringe. In addition, bioinformatics analyses, sequential ChIP and coimmunoprecipitation experiments reveal that Atro interacts with the Drosophila GAGA Factor, Trithorax-like (Trl), and they bind to the same loci simultaneously. Phenotypic analyses of Trl and Atro clones suggest that Atro is required to modulate the transcription activation by Trl in larval imaginal discs. Taken together, these data indicate that Atro is a major Trl cofactor that functions to moderate developmental gene transcription. DOI: http://dx.doi.org/10.7554/eLife.23084.001, eLife digest Cells with the same genetic information can look and behave differently to each other. This is because they can control the activity of their genes, changing the effects the genes have in the cell. Regulating genes in this way is important in allowing cells to adapt to their surroundings and to perform different tasks. Proteins called transcription factors control the activity of genes through other proteins called transcriptional co-activators and co-repressors. Atrophins are a group of co-repressors found in many animals including humans and fruit flies. Atrophins suppress the activity of certain genes, reducing the effects that they have in the cell. Losing Atrophin from cells can lead to severe diseases, but how Atrophin causes these effects is currently not well understood. Yeung et al. examined which genes Atrophin regulates in cells from the fruit fly Drosophila melanogaster. This investigation revealed that, amongst other genes, Atrophin controls several well-studied genes including engrailed and thickveins. These genes are important in allowing cells to communicate and co-ordinate before birth, ensuring cells work together to build complex tissues and organs. These results suggest Atrophin plays key roles in organising and shaping the body before birth. Further examination revealed that Atrophin acts in partnership with another molecule called Trithorax-like. Inside the cell many genes are protected by structures called nucleosomes that make them difficult to access, and Trithorax-like helps Atrophin to gain access to these genes. Further work will examine whether Atrophin and Trithorax-like work directly together or if other molecules bring about their interaction. It will also be important to examine how Atrophins suppress the activity of the genes they control. Errors in Atrophin1 in humans result in a nerve-damaging disease known as DRPLA; this work could also help researchers to better understand this disorder. DOI: http://dx.doi.org/10.7554/eLife.23084.002

Conditional stability constants of coordination complexes comprising divalent transition metals, Cu2+, Ni2+, Zn2+, Co2+, and ethylenediaminetetraacetic acid (EDTA) were determined utilizing electrospray ionization mass spectrometry. The deviation of signal response of a reference complex was monitored at addition of a second metal ion. The conditional stability constant for the competing metal was then determined through solution equilibria equations. The method showed to be applicable to a system where Co2+ and Zn2+ competed for EDTA at pH 5. When Cu2+ and Ni2+ competed for EDTA, the equilibrium changed over time. This change was shown to be affected in rate and size by the type of organic solvent added. In this work, 30% of either methanol or acetonitrile was used. It was found that if calibration curves are prepared for both metal complexes in solution and the measurements are repeated with sufficient time space, any change in equilibrium of sample solutions will be discovered. Copyright © 2014 John Wiley a Sons, Ltd. Copyright © 2014 John Wiley a Sons, Ltd.

The correlation between interaction parameters and ion flotation efficiency in mixtures of chelating surfactant metal complexes and different foaming agents was investigated. We have recently shown that chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) forms strong coordination complexes with divalent metal ions, and this can be utilized in ion flotation. Interaction parameters for mixed micelles and mixed monolayer formation for Mg(2+) and Ni(2+) complexes with the chelating surfactant 4-C12-DTPA and different foaming agents were calculated by Rubingh's regular solution theory. Parameters for the calculations were extracted from surface tension measurements and NMR diffusometry. The effects of metal ion coordination on the interactions between 4-C12-DTPA and the foaming agents could be linked to a previously established difference in coordination chemistry between the examined metal ions. As can be expected from mixtures of amphoteric surfactants, the interactions were strongly pH-dependent. Strong correlation was found between interaction parameter β(σ) for mixed monolayer formation and the phase-transfer efficiency of Ni(2+) complexes with 4-C12-DTPA during flotation in a customized flotation cell. In a mixture of Cu(2+) and Zn(2+), the significant difference in conditional stability constants (log K) between the metal complexes was utilized to selectively recover the metal complex with the highest log K (Cu(2+)) by ion flotation. Flotation experiments in an excess concentration of metal ions confirmed the coordination of more than one metal ion to the headgroup of 4-C12-DTPA.

Coordination complexes of some divalent metal ions with the DTPA (diethylenetriaminepentaacetic acid)-based chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) have been examined in terms of chelation and solution behavior. The headgroup of 4-C12-DTPA contains eight donor atoms that can participate in the coordination of a metal ion. Conditional stability constants for five transition metal complexes with 4-C12-DTPA were determined by competition measurements between 4-C12-DTPA and DTPA, using electrospray ionization mass spectrometry (ESI-MS). Small differences in the relative strength between the coordination complexes of DTPA and 4-C12-DTPA indicated that the hydrocarbon tail only affected the chelating ability of the headgroup to a limited extent. The coordination of Cu(2+) ions was investigated in particular, using UV-visible spectroscopy. By constructing Job's plots, it was found that 4-C12-DTPA could coordinate up to two Cu(2+) ions. Surface tension measurements and NMR diffusometry showed that the coordination of metal ions affected the solution behavior of 4-C12-DTPA, but there were no specific trends between the studied divalent metal complexes. Generally, the effects of the metal ion coordination could be linked to the neutralization of the headgroup charge of 4-C12-DTPA, and the resulting reduced electrostatic repulsions between adjacent surfactants in micelles and monolayers. The pH vs concentration plots, on the other hand, showed a distinct difference between 4-C12-DTPA complexes of the alkaline earth metals and the transition metals. This was explained by the difference in coordination between the two groups of metal ions, as predicted by the hard and soft acid and base (HSAB) theory.

Dabigatran is an oral direct thrombin inhibitor for which routine laboratory monitoring is currently not recommended. However, there are situations in which measurements of the drug and its effect are desirable. We therefore compared and validated different coagulation methods for assessments of dabigatran in clinical samples in relation to measurements of plasma dabigatran, without the purpose of establishing effective and safe concentrations of dabigatran in plasma.Samples were obtained from 70 atrial fibrillation patients treated with dabigatran etexilate. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were compared with coagulation methods Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as with prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT).A wide range of dabigatran concentrations was determined by LC-MS/MS (0.5-586 ng/mL). Correlations between LC-MS/MS results and estimated concentrations were excellent for both HTI and ECA overall (r(2) = 0.97 and 0.96 respectively, p0.0001), but the precision and variability of these assays were not fully satisfactory in the low range of dabigatran plasma concentrations, in which ECA performed better than HTI. aPTT performed poorly, and was normal (40 s) even with dabigatran levels of 60 ng/mL. PT-INR was normal even at supratherapeutic dabigatran concentrations.LC-MS/MS is the gold standard for measurements of dabigatran in plasma. Alternatively, either HTI or ECA assays may be used, but neither of these assays is dependable when monitoring low levels or to infer total absence of dabigatran. The aPTT assay is relatively insensitive to dabigatran, and normal aPTT results may be observed even with therapeutic dabigatran concentrations.

Epigenetic patterns of histone modifications contribute to the maintenance of tissue-specific gene expression. Here, we show that such modifications also accompany the specification of cell identities by the NF-κB transcription factor Dorsal in the precellular Drosophila embryo. We provide evidence that the maternal pioneer factor, Zelda, is responsible for establishing poised RNA polymerase at Dorsal target genes before Dorsal-mediated zygotic activation. At the onset of cell specification, Dorsal recruits the CBP/p300 coactivator to the regulatory regions of defined target genes in the presumptive neuroectoderm, resulting in their histone acetylation and transcriptional activation. These genes are inactive in the mesoderm due to transcriptional quenching by the Snail repressor, which precludes recruitment of CBP and prevents histone acetylation. By contrast, inactivation of the same enhancers in the dorsal ectoderm is associated with Polycomb-repressed H3K27me3 chromatin. Thus, the Dorsal morphogen gradient produces three distinct histone signatures including two modes of transcriptional repression, active repression (hypoacetylation), and inactivity (H3K27me3). Whereas histone hypoacetylation is associated with a poised polymerase, H3K27me3 displaces polymerase from chromatin. Our results link different modes of RNA polymerase regulation to separate epigenetic patterns and demonstrate that developmental determinants orchestrate differential chromatin states, providing new insights into the link between epigenetics and developmental patterning.

During cell specification, temporal and spatially restricted gene expression programs are set up, forming different cell types and ultimately a multicellular organism. In this thesis, we have studied the molecular mechanisms by which sequence specific transcription factors and coactivators regulate RNA polymerase II (Pol II) transcription to establish specific gene expression programs and what epigenetic patterns that follows. We found that the transcription factor Dorsal is responsible for establishing discrete epigenetic patterns in the presumptive mesoderm, neuroectoderm and dorsal ectoderm, during early Drosophila embryo development. In addition, these different chromatin states can be linked to distinct modes of Pol II regulation. Our results provide novel insights into how gene regulatory networks form an epigenetic landscape and how their coordinated actions specify cell identity. CBP/p300 is a widely used co-activator and histone acetyltransferase (HAT) involved in transcriptional activation. We discovered that CBP occupies the genome preferentially together with Dorsal, and has a specific role during development in coordinating the dorsal-ventral axis of the Drosophila embryo. While CBP generally correlates with gene activation we also found CBP in H3K27me3 repressed chromatin. Previous studies have shown that CBP has an important role at transcriptional enhancers. We provide evidence that the regulatory role of CBP does not stop at enhancers, but is extended to many genomic regions. CBP binds to insulators and regulates their activity by acetylating histones to prevent spreading of H3K27me3. We further discovered that CBP has a direct regulatory role at promoters. Using a highly potent CBP inhibitor in combination with ChIP and PRO-seq we found that CBP regulates promoter proximal pausing of Pol II. CBP promotes Pol II recruitment to promoters via a direct interaction with TFIIB, and promotes transcriptional elongation by acetylating the first nucleosome. CBP is regulating Pol II activity of nearly all expressed genes, however, either recruitment or release of Pol II is the rate-limiting step affected by CBP. Taken together, these results reveal mechanistic insights into cell specification and transcriptional control during development. At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

BACKGROUND: CREB-binding protein (CBP, also known as nejire) is a transcriptional co-activator that is conserved in metazoans. CBP plays an important role in embryonic development and cell differentiation and mutations in CBP can lead to various diseases in humans. In addition, CBP and the related p300 protein have successfully been used to predict enhancers in both humans and flies when they occur with monomethylation of histone H3 on lysine 4 (H3K4me1). RESULTS: Here, we compare CBP chromatin immunoprecipitation sequencing data from Drosophila S2 cells with modENCODE data and show that CBP is bound at genomic sites with a wide range of functions. As expected, we find that CBP is bound at active promoters and enhancers. In addition, we find that the strongest CBP sites in the genome are found at Polycomb response elements embedded in histone H3 lysine 27 trimethylated (H3K27me3) chromatin, where they correlate with binding of the Pho repressive complex. Interestingly, we find that CBP also binds to most insulators in the genome. At a subset of these, CBP may regulate insulating activity, measured as the ability to prevent repressive H3K27 methylation from spreading into adjacent chromatin. CONCLUSIONS: We conclude that CBP could be involved in a much wider range of functions than has previously been appreciated, including Polycomb repression and insulator activity. In addition, we discuss the possibility that a common role for CBP at all functional elements may be to regulate interactions between distant chromosomal regions and speculate that CBP is controlling higher order chromatin organization. Erratum to: CBP binding outside of promoters and enhancers in Drosophila melanogasterEpigenetics & Chromatin 2016 9:3810.1186/s13072-015-0042-4

In order for a new organism to form, the genomes of the highly specialized egg and sperm need to be reprogrammed into a totipotent state that is capable of generating all of the cell types that comprise an organism. This reprogramming occurs by erasing chromatin modifications, leaving the cells in a naïve state, followed by the induction of specialized programming events. Pioneer factors bind to the genome prior to zygotic genome activation, followed by acetylation of histones and further chromatin specialization by the addition of methylation marks later during differentiation. Genome-wide approaches have provided insight into the genomic and epigenomic regulation of gene expression during development, providing a new perspective on the process of cell specification and differentiation. In this review, we discuss how distal DNA and core promoter elements, RNA polymerase pausing, transcription factors, and co-regulators interact to shape the chromatin landscape and direct tissue-specific expression patterns during embryo development, focusing on the well-characterized Drosophila embryo.

We have determined drug partitioning into phospholipid bilayers by immobilized-liposome chromatography (ILC). Electrostatic effects on the drug partitioning were observed on neutral bilayers at low ionic strength. The size of the counterions affected the partitioning. When liposomes were supplemented with ionic detergents the partitioning of charged drugs was strongly affected, allowing complete separation of drugs of different charges which showed similar retention on neutral bilayers. Partial separation was obtained on bilayers containing fatty acid. Detergent ions or fatty acid inserted into phospholipid bilayers affected the partitioning of drugs much more than did free ions or phospholipid head group charges.

Transcription activation involves RNA polymerase II (Pol II) recruitment and release from the promoter into productive elongation, but how specific chromatin regulators control these steps is unclear. Here, we identify a novel activity of the histone acetyltransferase p300/CREB-binding protein (CBP) in regulating promoter-proximal paused Pol II. We find that Drosophila CBP inhibition results in "dribbling" of Pol II from the pause site to positions further downstream but impedes transcription through the +1 nucleosome genome-wide. Promoters strongly occupied by CBP and GAGA factor have high levels of paused Pol II, a unique chromatin signature, and are highly expressed regardless of cell type. Interestingly, CBP activity is rate limiting for Pol II recruitment to these highly paused promoters through an interaction with TFIIB but for transit into elongation by histone acetylation at other genes. Thus, CBP directly stimulates both Pol II recruitment and the ability to traverse the first nucleosome, thereby promoting transcription of most genes.

Conditional stability constants of coordination complexes comprising divalent transition metals, Cu(2+), Ni(2+), Zn(2+), Co(2+), and ethylenediaminetetraacetic acid (EDTA) were determined utilizing electrospray ionization mass spectrometry. The deviation of signal response of a reference complex was monitored at addition of a second metal ion. The conditional stability constant for the competing metal was then determined through solution equilibria equations. The method showed to be applicable to a system where Co(2+) and Zn(2+) competed for EDTA at pH 5. When Cu(2+) and Ni(2+) competed for EDTA, the equilibrium changed over time. This change was shown to be affected in rate and size by the type of organic solvent added. In this work, 30% of either methanol or acetonitrile was used. It was found that if calibration curves are prepared for both metal complexes in solution and the measurements are repeated with sufficient time space, any change in equilibrium of sample solutions will be discovered.

Introduktion: Diabetes Typ 2 är ett världsomfattande hälsoproblem. Sjukdomen är ärftligmen beror till största del på levnadsvanor. Livstilen påverkar allvarlighetsgraden avsjukdomen. Denna rapport fokuserar uteslutande på typ 2-diabetes mellitus (T2DM). Hur välegenvården fungerar påverkar prognosen hos personer med T2DM. Syfte: Syftet är att genomen litteraturöversikt belysa hur livsstilsintervention påverkar personer med T2DM. Metod:Denna literaturöversikt baseras på 13 vetenskapliga artiklar med kvantitativ, kvalitativ ochmixad ansats. Resultat: Resultatet visade att motiverande samtal och gruppdiskussioner varett effektivt sätt att höja motivation och kunskapsnivån hos personer med T2DM. Kost ochträningsinterventioner hade sin främsta styrka i att signifikant förbättra fysiologiska aspektersom t.ex. HbA1c och midjemått, men även psykologiska förbättringar kunde ses, somminskad oro för kardiovaskulära sjukdomar. Tekniska hjälpmedel för egenvårdåskådliggjorde sambandet mellan levnadsvanor och glykemisk kontroll. Diskussion: Vi anseratt det inte finns ett överlägset alternativ av interventionerna, vi vill belysa vikten av stegvisförändring, med början på en intervention för att öka motivationen. Det är viktigt attinterventionen känns meningsfull för individen. Slutsats: Det kan i verkligheten vara svårt attuppnå en helt individbaserad vård, vi anser med detta i åtanke att motiverande samtal är denbästa standardiserade lösningen.

t Boija, L & Stark Isaksson, M. (2013) Förskolans arbete med barns fysiska hälsa – En enkätundersökning om tre förskolors arbete med barns fysiska hälsa. Examensarbete i pedagogik 15hp. Lärarprogrammet, akademin för utbildning och ekonomi. Högskolan i Gävle. Barns hälsa är ett stort område som alltid diskuteras på olika sätt. Trötta, stressade, överviktiga och med koncentrationssvårigheter är de ord som ofta beskriver dagens barn och unga. Syftet med denna studie är att undersöka om pedagogerna på berörda förskolor anser sig ha tillräcklig kunskap, tillgång till lokaler och andra förutsättningar för att ge barnen tillfälle till planerade fysiska aktiviteter. Fysiska aktiviteter är beroende av pigga, koncentrerade och inte stressade barn för att minimera skador vid lek och annan aktivitet. För att nå dit brukar kosten komma på tal vilket har gjort att vi även valt att lägga lite fokus på att se över livsmedelsverkets riktlinjer och de pedagogiska måltiderna. Vi valde att göra kvantitativa enkätundersökningar med hjälp av 31 pedagoger i två olika kommuner för att få svar på våra frågor. Resultatet visar på deras likheter och olikheter i arbetet med fysisk aktivitet inom förskolorna. Resultatet pekar även på att skillnader finns på utövandet av planerade fysiska aktiviteter beroende på om pedagogerna anser sig ha tillgång till anpassade lokaler. Vidare visar även resultatet att måltiderna skiljer sig åt på de olika förskolorna. Nyckelord: Pedagogik, förskola, fysisk hälsa.

Titel Att kommunicera svår förändring - Ett medarbetarperspektiv Författare Therése Boija & Fanny Nyberg Handledare Catrin Johansson Examinator Elisabeth Stúr Utbildning Medie- och kommunikationsvetenskap, HT 2011, Mittuniversitetet Syfte Syftet med studie är att ta reda på hur medarbetare från tre olika arbetsplatser inom Spendrups uppfattar kommunikationen kring förändringen på Vårby bryggeri. Frågeställningar Hur den dagliga kommunikationen mellan chefer och medarbetare upplevs av medarbetarna. Hur medarbetarna vill att kommunikationen mellan chefer och medarbetare ska fungera. Hur medarbetarna upplever kommunikationen kring nedläggningen. Metod Studien har gjorts i form av nio fokusgrupper bestående av 3-5 deltagare från Spendrups medarbetare. Resultat I studien framgår det att Spendrups förändringskommunikation fungerar bra initialt men saknar uppföljning. Dessutom vill medarbetarna i regel ha en mer tillgänglig chef. De tillfrågade medarbetarna anser att kommunikationen i organisationen oftast sker muntligt, och de vill ha det så, men att informationen inte är tillräcklig. Detta har resulterat i ryktesspridning och en del oro, främst på bryggerierna i Vårby och Hällefors. Nyckelord Förändringskommunikation, intern kriskommunikation, medarbetarskap, ryktesspridning, kommunikationsprocesser, förändringsprocesser.