BMP4-BMPR1A Signaling in β Cells Is Required for and Augments Glucose-Stimulated Insulin Secretion

SummaryImpaired glucose-stimulated insulin secretion (GSIS) and perturbed proinsulin processing are hallmarks of β cell dysfunction in type 2 diabetes. Signals that can preserve and/or enhance β cell function are therefore of great therapeutic interest. Here we show that bone morphogenetic protein 4 (Bmp4) and its high-affinity receptor, Bmpr1a, are expressed in β cells. Mice with attenuated BMPR1A signaling in β cells show decreased expression of key genes involved in insulin gene expression, proinsulin processing, glucose sensing, secretion stimulus coupling, incretin signaling, and insulin exocytosis and develop diabetes due to impaired insulin secretion. We also show that transgenic expression of Bmp4 in β cells enhances GSIS and glucose clearance and that systemic administration of BMP4 protein to adult mice significantly stimulates GSIS and ameliorates glucose tolerance in a mouse model of glucose intolerance. Thus, BMP4-BMPR1A signaling in β cells plays a key role in GSIS

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

Primary school teachers’ patterns in using communication-supporting strategies following a professional development program: lessons learned from an exploratory study with three teachers

Oral language skills underpin later literacy achievement and life prospects, and many children struggle with oral language for various reasons. Hence, it is crucial for teachers to provide a learning environment with rich opportunities for all children to practice their oral language. The aim of this exploratory study was to explore a professional development (PD) program designed to coach teachers in using communication-supporting strategies during verbal teacher-child interactions in regular classrooms. In focus were five strategies from the Communication Supporting Classroom Observation Tool. The study used a mixed-method case design with multiple observations across four time points over 10 weeks and a follow-up observation after two months. Outcome measures were collected at pre-and, post-intervention and at follow-up. The cases were two intervention teachers and one comparison teacher in second grade in Swedish primary schools. The teachers were directly observed and video-recorded during teacher-child structured small group conversations while discussing different texts with two groups of children each. The groups were mixed and comprised both children struggling with oral language as well as more typically developing children. To further understand the verbal interactions, the teachers’ amount of talk in relation to the children was analyzed in terms of the percentage distribution of the total number of words per minute. The overall patterns of strategy use showed that the two intervention teachers applied more varied strategies from the PD program during the intervention period, but this was not maintained at the follow-up. The amount of teacher talk appeared stable over time, with individual differences in the three teachers. We also discuss the teachers’ own insights and our experience in the design of the PD program, which may guide future research and applications of the PD program

Реконструкция системы электроснабжения ОАО «Салео-Гомель» в связи с модернизацией механического цеха № 2

The insulin-degrading enzyme (IDE) degrades amyloidogenic proteins such as Amyloid β (Aβ) and Islet Amyloid Polypeptide (IAPP), i.e. peptides associated with Alzheimer's disease and type 2 diabetes, respectively. In addition to the protease activity normally associated with IDE function an additional activity involving the formation of stable, irreversible complexes with both Aβ and α-synuclein, an amyloidogenic protein involved in Parkinson's disease, was recently proposed. Here, we have investigated the functional consequences of IDE-α-synuclein interactions in vitro. We demonstrate that IDE in a nonproteolytic manner and at sub-stoichiometric ratios efficiently inhibits α-synuclein fibril formation by binding to α-synuclein oligomers making them inert to amyloid formation. Moreover, we show that, within a defined range of α-synuclein concentrations, interaction with α-synuclein oligomers increases IDE's proteolytic activity on a fluorogenic substrate. We propose that the outcomes of IDE-α-synuclein interactions, i.e. protection against α-synuclein amyloid formation and stimulated IDE protease activity, may be protective in vivo

Later Stone Age human hair from Vaalkrans Shelter, Cape Floristic Region of South Africa, reveals genetic affinity to Khoe groups

Abstract: Please refer to full text to view abstract

Retinoic Acid Promotes the Generation of Pancreatic Endocrine Progenitor Cells and Their Further Differentiation into β-Cells

The identification of secreted factors that can selectively stimulate the generation of insulin producing β-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based β-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of β-cells during normal pancreatic development such putative factors may be identified. In the mouse, β-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of β-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when β-cells are generated. We also provide evidence that RA induces the generation of Ngn3+ endocrine progenitor cells and stimulates their further differentiation into β-cells by activating a program of cell differentiation that recapitulates the normal temporal program of β-cell differentiation

Predicting complete loss to follow-up after a health-education program: number of absences and face-to-face contact with a researcher

<p>Abstract</p> <p>Background</p> <p>Research on health-education programs requires longitudinal data. Loss to follow-up can lead to imprecision and bias, and <it>complete </it>loss to follow-up is particularly damaging. If that loss is predictable, then efforts to prevent it can be focused on those program participants who are at the highest risk. We identified predictors of complete loss to follow-up in a longitudinal cohort study.</p> <p>Methods</p> <p>Data were collected over 1 year in a study of adults with chronic illnesses who were in a program to learn self-management skills. Following baseline measurements, the program had one group-discussion session each week for six weeks. Follow-up questionnaires were sent 3, 6, and 12 months after the baseline measurement. A person was classified as completely lost to follow-up if none of those three follow-up questionnaires had been returned by two months after the last one was sent.</p> <p>We tested two hypotheses: that complete loss to follow-up was directly associated with the number of absences from the program sessions, and that it was less common among people who had had face-to-face contact with one of the researchers. We also tested predictors of data loss identified previously and examined associations with specific diagnoses.</p> <p>Using the unpaired t-test, the U test, Fisher's exact test, and logistic regression, we identified good predictors of complete loss to follow-up.</p> <p>Results</p> <p>The prevalence of complete loss to follow-up was 12.2% (50/409). Complete loss to follow-up was directly related to the number of absences (odds ratio; 95% confidence interval: 1.78; 1.49-2.12), and it was inversely related to age (0.97; 0.95-0.99). Complete loss to follow-up was less common among people who had met one of the researchers (0.51; 0.28-0.95) and among those with connective tissue disease (0.29; 0.09-0.98). For the multivariate logistic model the area under the ROC curve was 0.77.</p> <p>Conclusions</p> <p>Complete loss to follow-up after this health-education program can be predicted to some extent from data that are easy to collect (age, number of absences, and diagnosis). Also, face-to-face contact with a researcher deserves further study as a way of increasing participation in follow-up, and health-education programs should include it.</p

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Vi är inte här för att måla vackert : - Fem bildlärares syn på sitt ämne

Syftet med studien är att genom intervjuer undersöka hur fem bildlärare ser på sitt ämne och om de fokuserar bildkommunikation eller bildskapande. Studien visar att det kommunikativa begreppet upplevs som komplext och svårbegripligt. Därmed tolkas det på många olika sätt av bildlärarna. De tycks välja det sätt som passar in i deras synsätt och i undervisning. Undersökning baserat på forskningslitteratur samt kursplaner. Dessa tyder på att det kommunikativa har hamnat i skuggan av skapandeprocessen, men i uppsatsen lyfts även vikten av skapandet fram. Flera forskare menar att de båda begreppen bildskapande och bildkommunikationen kompletterar varandra. Resultatet tyder på att en förändring tycks vara på väg, trots att forskningen pekar åt annat håll