Gene array identification of Ipf1/Pdx1-/- regulated genes in pancreatic progenitor cells

<p>Abstract</p> <p>Background</p> <p>The homeodomain transcription factor IPF1/PDX1 exerts a dual role in the pancreas; <it>Ipf1/Pdx1 </it>global null mutants fail to develop a pancreas whereas conditional inactivation of <it>Ipf1/Pdx1 </it>in β-cells leads to impaired β-cell function and diabetes. Although several putative target genes have been linked to the β-cell function of <it>Ipf1/Pdx1</it>, relatively little is known with respect to genes regulated by IPF1/PDX1 in early pancreatic progenitor cells.</p> <p>Results</p> <p>Microarray analyses identified a total of 111 genes that were differentially expressed in e10.5 pancreatic buds of <it>Ipf1/Pdx1</it>^-/-embryos. The expression of one of these, <it>Spondin 1</it>, which encodes an extracellular matrix protein, has not previously been described in the pancreas. Quantitative real-time RT-PCR analyses and immunohistochemical analyses also revealed that the expression of <it>FgfR2IIIb</it>, that encodes the receptor for FGF10, was down-regulated in <it>Ipf1/Pdx1</it>^-/-pancreatic progenitor cells.</p> <p>Conclusion</p> <p>This microarray analysis has identified a number of candidate genes that are differentially expressed in <it>Ipf1/Pdx1</it>^-/-pancreatic buds. Several of the differentially expressed genes were known to be important for pancreatic progenitor cell proliferation and differentiation whereas others have not previously been associated with pancreatic development.</p

Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease.

RATIONALE: The alveolar pathology in chronic obstructive pulmonary disease (COPD) involves antigen-driven immune events. However, the induction sites of alveolar adaptive immune responses have remained poorly investigated. OBJECTIVES: To explore the hypothesis that interfaces between the alveolar lumen and lymphoid aggregates (LAs) provide a structural basis for increased alveolar antigen uptake in COPD lungs. METHODS: Lung samples from patients with mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), moderate-severe (GOLD II-III), and very severe (GOLD IV) COPD were subjected to detailed histological assessments of adaptive immune system components. Never smokers and smokers without COPD served as controls. RESULTS: Quantitative histology, involving computerised three-dimensional reconstructions, confirmed a rich occurrence of alveolar-restricted LAs and revealed, for the first time, that the vast majority of vascular or bronchiolar associated LAs had alveolar interfaces but also an intricate network of lymphatic vessels. Uniquely to COPD lungs, the interface epithelium had transformed into a columnar phenotype. Accumulation of langerin (CD207)(+) dendritic cells occurred in the interface epithelium in patients with COPD but not controls. The antigen-capturing capacity of langerin(+) dendritic cells was confirmed by increased alveolar protrusions and physical T cell contact. Several of these immune remodelling parameters correlated with lung function parameters. CONCLUSIONS: Severe stages of COPD are associated with an emergence of remodelled and dendritic cell-rich alveolar-lymphoid interfaces. This novel type of immune remodelling, which predicts an increased capacity to respond to alveolar antigens, is suggested to contribute to aggravated inflammation in COPD

Leys from a Nordic perspective

The project involved creating a popular scientific review of the cultivation and use of leys for livestock. Target groups are the agricultural sector and industry. The project had four work packages (WP): crop production, harvest and conservation, feed value for different animals, and economy. Within each work package, search strings were developed and inclusion criteria defined, and a database for each WP developed through searching in online databases. Each selected article was assessed first on the title (include or exclude), second based on reading the abstract, and third based on reading the article. The review provides an extensive list of literature related to ley production and use, a description of the most important findings, and suggestions for future research

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

The role of nuclear envelope proteins in chromatin organization, differentiation and disease

In eukaryotes the genetic material is separated from the cytoplasm by the nuclear envelope (NE), consisting of the outer and inner nuclear membrane, the nuclear lamina and the nuclear pores. The genetic material is highly structured with transcriptionally inactive heterochromatin enriched at the nuclear periphery and transcriptionally active euchromatin in the nuclear interior. Underlying the inner nuclear membrane is the nuclear lamina (nucleoskeleton) that together with several hundred nuclear envelope transmembrane proteins (NETs) connect chromatin to the nuclear periphery. Most NETs are uncharacterized and expressed in a tissue-specific manner. Mutations in NE proteins are linked to distinct degenerative disorders, referred to as envelopathies or laminopathies. The NET primarily studied in this thesis is called Spindle-Associated Membrane Protein 1 (Samp1). We showed that overexpression of Samp1 induced a fast differentiation of human induced pluripotent stem cells and that the binding between two NETs, Samp1 and Emerin, is regulated by RanGTP. Another focus of this thesis was the development and use of a novel method called Fluorescent Ratiometric Imaging of Chromatin (FRIC). FRIC quantitatively monitors the epigenetic state of chromatin in live cells. Using FRIC, we were able to show that Samp1 promotes peripheral heterochromatin organization. FRIC also detected an increased distribution of heterochromatin at the nuclear periphery during neuronal differentiation. In conclusion, FRIC is a useful tool that could serve medical research in elucidating the effects of different chemical agents and the roles of NE proteins in chromatin organization

“I never have enough time to finish my to-do list” : A diary study showing how full-time employees with flexible working hours use their time

Titel: “Jag hinner aldrig igenom min ‘to do’-lista” Undertitel: En dagboksstudie om hur heltidsanställda med flexibelt arbete använder sin tid Författare: Cecilia Bergqvist och Larglinda Sopaj Handledare: Jean-Charles Languilaire Nivå: Kandidatuppsats inom företagsekonomi, vårterminen 2019 (15 hp) Nyckelord: flextid, flexibelt arbete, övertid, work-life conflict, gränslöst arbete, time, time management Forskningsfråga: Hur använder heltidsanställda med flexibelt arbete sin tid? Syfte: Att beskriva hur heltidsanställda med flexibelt arbete använder sin tid. Metod: Studien bygger på ett praktiskt problem med begränsad tidigare forskning om ämnet. Därför tillämpades ett induktivt tillvägagångssätt för att svara på studiens syfte. Forskarnas vetenskapliga förhållningssätt är hermeneutiskt. Empiriska data samlades in genom kvalitativa och kvantitativa frågor och analyserades därefter på ett kvalitativt sätt som en tematisk analys. Empirisk insamling: Empiriska data samlades in genom en dagbok på 5-arbetsdagar, rapporterad av 15 deltagare. För att delta i dagbokstudien krävdes att individen uppfyllde två kriterier, att: 1) vara heltidsanställda och 2) ha flexibla arbetstider. Dagboken innehöll både kvalitativa och kvantitativa frågor. Resultat och slutsats: Eftersom resultatet visar på att 73,3% av deltagarna arbetade övertid, är det då rimligt att dra slutsatsen att flexibelt arbete kan leda till att individer arbetar övertid. På grund av att deltagarna arbetade övertid påverkades deltagarnas fritid ofta negativt. Många av deltagarna hade konflikter mellan arbetsrollen och privatrollen, vilket resulterade i att dessa roller var inkompatibla. Konflikterna visades ofta genom att deltagarna avbokade eller bortprioriterade fysiska aktiviteter på grund av övertid. Resultatet visade på att anställda hade god time management och använde sin tid effektivt, men obalans mellan inflöde och utflöde av arbetsuppgifter resulterade i att anställda ofta kände att de inte hann klart med sina arbetsuppgifter. Resultaten visade även ett svagt positivt samband mellan nöjdhet över dagens arbetsinsats och påverkat välmående. Deltagarna som hade barn som bodde hemma brukade ofta ha ett mer strukturerade arbetsrutiner, medan individer som inte var föräldrar eller barnen hade flyttat hemifrån, brukade ofta ha mindre strukturerade arbetsrutiner.Title: “I never have enough time to finish my to-do list” Subtitle: A diary study showing how full-time employees with flexible working hours use their time. Authors: Cecilia Bergqvist and Larglinda Sopaj Advisor: Jean-Charles Languilaire Level: Bachelor thesis in Business Administration, Spring 2019 (15 credits) Keywords: flextime, flexible work, overtime, work-life conflict, boundaryless work, time, time management Question: How do full-time employees with flexible working hours use their time? Purpose: Describe how full-time employees with flexible working hours use their time. Method: The study is based on a practical problem with limited previous studies on the matter. Therefore, an inductive approach was implemented to answer the purpose of the study and the researchers’ scientific approach to data is hermeneutic. Empirical data was collected through qualitative and quantitative questions, and thereafter analyzed in a qualitative manner as a thematic analysis. Empirical framework: Empirical data was collected by a 5-workday diary reported by 15 participants. To participate in the diary study, an individual had to meet two criteria: (1) they must be full-time employee and (2) must have flexible working hours. The diary included both qualitative and quantitative-based questions. Results and conclusion: Since the results show that 73.3% of participants were working overtime, it is reasonable to conclude that flexible working hours can lead to individuals working overtime. Furthermore, due to the overtime, participants’ spare time was often affected negatively. Indeed, many participants had work-life conflicts, where the work-life and the private life were incompatible. This phenomenon is evident through reported cancelled or rebooked physical training due to extended working hours. Additionally, participants who had minor children usually had a more coherent and predictable working schedule. On the other hand, individuals who were not parents of minor children had less coherent and less predictable working schedule. The results from the study also showed that the participants had good time management and used their time effectively, but the consistent imbalance between ingoing work tasks and outgoing work tasks resulted in participants often felt like they never finished their task assignments. The results also showed a slight positive correlation between satisfaction over the work effort of the day and the impact on well-bein

“I never have enough time to finish my to-do list” : A diary study showing how full-time employees with flexible working hours use their time

Titel: “Jag hinner aldrig igenom min ‘to do’-lista” Undertitel: En dagboksstudie om hur heltidsanställda med flexibelt arbete använder sin tid Författare: Cecilia Bergqvist och Larglinda Sopaj Handledare: Jean-Charles Languilaire Nivå: Kandidatuppsats inom företagsekonomi, vårterminen 2019 (15 hp) Nyckelord: flextid, flexibelt arbete, övertid, work-life conflict, gränslöst arbete, time, time management Forskningsfråga: Hur använder heltidsanställda med flexibelt arbete sin tid? Syfte: Att beskriva hur heltidsanställda med flexibelt arbete använder sin tid. Metod: Studien bygger på ett praktiskt problem med begränsad tidigare forskning om ämnet. Därför tillämpades ett induktivt tillvägagångssätt för att svara på studiens syfte. Forskarnas vetenskapliga förhållningssätt är hermeneutiskt. Empiriska data samlades in genom kvalitativa och kvantitativa frågor och analyserades därefter på ett kvalitativt sätt som en tematisk analys. Empirisk insamling: Empiriska data samlades in genom en dagbok på 5-arbetsdagar, rapporterad av 15 deltagare. För att delta i dagbokstudien krävdes att individen uppfyllde två kriterier, att: 1) vara heltidsanställda och 2) ha flexibla arbetstider. Dagboken innehöll både kvalitativa och kvantitativa frågor. Resultat och slutsats: Eftersom resultatet visar på att 73,3% av deltagarna arbetade övertid, är det då rimligt att dra slutsatsen att flexibelt arbete kan leda till att individer arbetar övertid. På grund av att deltagarna arbetade övertid påverkades deltagarnas fritid ofta negativt. Många av deltagarna hade konflikter mellan arbetsrollen och privatrollen, vilket resulterade i att dessa roller var inkompatibla. Konflikterna visades ofta genom att deltagarna avbokade eller bortprioriterade fysiska aktiviteter på grund av övertid. Resultatet visade på att anställda hade god time management och använde sin tid effektivt, men obalans mellan inflöde och utflöde av arbetsuppgifter resulterade i att anställda ofta kände att de inte hann klart med sina arbetsuppgifter. Resultaten visade även ett svagt positivt samband mellan nöjdhet över dagens arbetsinsats och påverkat välmående. Deltagarna som hade barn som bodde hemma brukade ofta ha ett mer strukturerade arbetsrutiner, medan individer som inte var föräldrar eller barnen hade flyttat hemifrån, brukade ofta ha mindre strukturerade arbetsrutiner.Title: “I never have enough time to finish my to-do list” Subtitle: A diary study showing how full-time employees with flexible working hours use their time. Authors: Cecilia Bergqvist and Larglinda Sopaj Advisor: Jean-Charles Languilaire Level: Bachelor thesis in Business Administration, Spring 2019 (15 credits) Keywords: flextime, flexible work, overtime, work-life conflict, boundaryless work, time, time management Question: How do full-time employees with flexible working hours use their time? Purpose: Describe how full-time employees with flexible working hours use their time. Method: The study is based on a practical problem with limited previous studies on the matter. Therefore, an inductive approach was implemented to answer the purpose of the study and the researchers’ scientific approach to data is hermeneutic. Empirical data was collected through qualitative and quantitative questions, and thereafter analyzed in a qualitative manner as a thematic analysis. Empirical framework: Empirical data was collected by a 5-workday diary reported by 15 participants. To participate in the diary study, an individual had to meet two criteria: (1) they must be full-time employee and (2) must have flexible working hours. The diary included both qualitative and quantitative-based questions. Results and conclusion: Since the results show that 73.3% of participants were working overtime, it is reasonable to conclude that flexible working hours can lead to individuals working overtime. Furthermore, due to the overtime, participants’ spare time was often affected negatively. Indeed, many participants had work-life conflicts, where the work-life and the private life were incompatible. This phenomenon is evident through reported cancelled or rebooked physical training due to extended working hours. Additionally, participants who had minor children usually had a more coherent and predictable working schedule. On the other hand, individuals who were not parents of minor children had less coherent and less predictable working schedule. The results from the study also showed that the participants had good time management and used their time effectively, but the consistent imbalance between ingoing work tasks and outgoing work tasks resulted in participants often felt like they never finished their task assignments. The results also showed a slight positive correlation between satisfaction over the work effort of the day and the impact on well-bein

An inner nuclear membrane protein induces rapid differentiation of human induced pluripotent stem cells

The ability of iPSCs (induced pluripotent stem cells) to generate any cell type in the body makes them valuable tools for cell replacement therapies. However, differentiation of iPSCs can be demanding, slow and variable. During differentiation chromatin is re-organized and silent dense heterochromatin becomes tethered to the nuclear periphery by processes involving the nuclear lamina and proteins of the INM (inner nuclear membrane). The INM protein, Samp1 (Spindle Associated Membrane Protein 1) interacts with Lamin A/C and the INM protein Emerin, which has a chromatin binding LEM (Lap2-Emerin-Man1)-domain. In this paper we investigate if Samp1 can play a role in the differentiation of iPSCs. Samp1 levels increased as differentiating iPSCs started to express Lamin A/C. Interestingly, even under pluripotent culturing conditions, ectopic expression of Samp1 induced a rapid differentiation of iPSCs, of which some expressed the neuronal marker βIII-tubulin already after 6 days. This suggests that Samp1 is involved in early differentiation of iPSCs and could potentially be explored as a tool to promote progression of the differentiation process

Alveolar T-helper type-2 immunity in atopic asthma is associated with poor clinical control

Real-world evaluation studies have shown that many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICSs). As conventional ICSs have poor access to the peripheral airways, the aim of the present paper was to study the relationship between peripheral airway inflammation and clinical control in allergic asthma. Consequently, bronchial and transbronchial biopsies were obtained from patients with poorly controlled asthma [n=12, asthma control test (ACT) score = 20) and healthy controls (n= 8). Tissue sections were immunostained to assess multiple leucocyte populations. To determine the degree of T-helper type-2 (Th2) immunity, the logarithmic value of the ratio between Th2 cells/mm(2) and Th1 cells/mm(2) was used as a surrogate score for Th2-skewed immunity. In the bronchi, the leucocyte infiltration pattern and the Th2-score were similar between patients with well-controlled asthma and those with poorly controlled asthma. In contrast, in the alveolar parenchyma, the expression of T-helper cells was significantly higher in patients with poorly controlled asthma than in patients with well-controlled asthma (P < 0.01). Furthermore, the alveolar Th2-score was significantly higher in patients with poorly controlled asthma (median 0.4) than in the controlled patients (median -0.10, P < 0.05). In addition, in contrast with bronchial Th2-score, the alveolar Th2-score correlated significantly with ACT score (r(s)=-0.62, P < 0.01) in the pooled asthma group. Collectively, our data reveal an alveolar Th2-skewed inflammation, specifically in asthmatic patients who are poorly controlled with ICSs, and suggest that pharmacological targeting of the peripheral airways may be beneficial in this large patient category