| 1. |
- Valiente-Dobon, J. J., et al.
(författare)
-
Conceptual design of the AGATA 2 pi array at LNL
- 2023
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 1049
-
Tidskriftsartikel (refereegranskat)abstract
- The Advanced GAmma Tracking Array (AGATA) has been installed at Laboratori Nazionali di Legnaro (LNL), Italy. In this installation, AGATA will consist, at the beginning, of 13 AGATA triple clusters (ATCs) with an angular coverage of 1n,and progressively the number of ATCs will increase up to a 2 pi angular coverage. This setup will exploit both stable and radioactive ion beams delivered by the Tandem-PIAVE-ALPI accelerator complex and the SPES facility. The new implementation of AGATA at LNL will be used in two different configurations, firstly one coupled to the PRISMA large-acceptance magnetic spectrometer and lately a second one at Zero Degrees, along the beam line. These two configurations will allow us to cover a broad physics program, using different reaction mechanisms, such as Coulomb excitation, fusion-evaporation, transfer and fission at energies close to the Coulomb barrier. These setups have been designed to be coupled with a large variety of complementary detectors such as charged particle detectors, neutron detectors, heavy-ion detectors, high-energy gamma-ray arrays, cryogenic and gasjet targets and the plunger device for lifetime measurements. We present in this paper the conceptual design, characteristics and performance figures of this implementation of AGATA at LNL.
|
|
| 2. |
|
|
| 3. |
- Lindqvist, A, et al.
(författare)
-
Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels
- 2020
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 511
-
Tidskriftsartikel (refereegranskat)abstract
- It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.
|
|
| 4. |
- Salami, F, et al.
(författare)
-
DETECTION OF LACTOBACILLI IN MONTHLY MAIL-IN STOOL SAMPLES FROM 3-18 MONTHS OLD INFANTS AT GENETIC RISK FOR TYPE 1 DIABETES
- 2012
-
Ingår i: International journal of probiotics & prebiotics. - 1555-1431. ; 7:3-4, s. 135-144
-
Tidskriftsartikel (refereegranskat)abstract
- The feasibility to detect lactobacilli in mail-in infant stools collected monthly from 3-18 months old children was investigated. The aim was to determine total lactobacilli and Lactobacillus plantarum (L. plantarum) content (ng/g feces) in 50 infants each from Colorado (648 samples), Finland (624 samples) and Sweden (685 samples) who participated in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. Total lactobacilli content varied markedly between 5 and 16,800 ng/g feces in the three clinical sites within and between individuals especially in infants. L.plantarum also varied markedly intra- and inter-individually from <0.5 - 736 ng/g feces. A higher variability of total lactobacilli was found before 10 months of age than after in the three different clinical sites. Sweden had the lowest total lactobacilli content compared to Colorado and Finland while the L.plantarum content was higher in Sweden. Mail-in stool samples from infants should prove useful in analyzing probiotics in childhood.
|
|
| 5. |
- Abels, Esther, et al.
(författare)
-
Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the Digital Pathology Association
- 2019
-
Ingår i: Journal of Pathology. - : WILEY. - 0022-3417 .- 1096-9896. ; 249:3, s. 286-294
-
Forskningsöversikt (refereegranskat)abstract
- In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. (c) 2019 The Authors. The Journal of Pathology published by John Wiley amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
|
|
| 6. |
- Andersson, Birger, et al.
(författare)
-
Towards a common ontology for business models
- 2006
-
Ingår i: CEUR Workshop Proceedings.
-
Konferensbidrag (refereegranskat)abstract
- To create an understanding of enterprises and the ways they do business, a starting point could be to identify the main actors and the values transferred between them. Business models are created in order to make clear who the business actors are in a business case and to make their relations explicit. The relations are formulated in terms of values exchanged between the actors. The purpose of the work reported in this paper is to create a better understanding of business models by identifying basic notions used in such models. It does so by constructing a common ontology based on three established business model ontologies: e3-value, REA, and BMO. By means of a careful analysis of these ontologies a conceptual schema is created that defines the common concepts. An example is worked out that explains how the common ontology should be understood.
|
|
| 7. |
- Chriett, S., et al.
(författare)
-
SCRT1 is a novel beta cell transcription factor with insulin regulatory properties
- 2021
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 521
-
Tidskriftsartikel (refereegranskat)abstract
- Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.
|
|
| 8. |
- Lindqvist, Andreas, et al.
(författare)
-
GPR162 is a beta cell CART receptor
- 2023
-
Ingår i: iScience. - 2589-0042. ; 26:12
-
Tidskriftsartikel (refereegranskat)abstract
- Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.
|
|
| 9. |
- Nicholas, Lisa M., et al.
(författare)
-
Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic β-cells
- 2017
-
Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 6:7, s. 651-663
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Insulin release from pancreatic β-cells is controlled by plasma glucose levels via mitochondrial fuel metabolism. Therefore, insulin secretion is critically dependent on mitochondrial DNA (mtDNA) and the genes it encodes. Mitochondrial transcription factor B2 (TFB2M) controls transcription of mitochondrial-encoded genes. However, its precise role in mitochondrial metabolism in pancreatic β-cells and, consequently, in insulin secretion remains unknown. Methods: To elucidate the role of TFB2M in mitochondrial function and insulin secretion in vitro and in vivo, mice with a β-cell specific homozygous or heterozygous knockout of Tfb2m and rat clonal insulin-producing cells in which the gene was silenced were examined with an array of metabolic and functional assays. Results: There was an effect of gene dosage on Tfb2m expression and function. Loss of Tfb2m led to diabetes due to disrupted transcription of mitochondrial DNA (mtDNA) and reduced mtDNA content. The ensuing mitochondrial dysfunction activated compensatory mechanisms aiming to limit cellular dysfunction and damage of β-cells. These processes included the mitochondrial unfolded protein response, mitophagy, and autophagy. Ultimately, however, these cell-protective systems were overridden, leading to mitochondrial dysfunction and activation of mitochondrial-dependent apoptotic pathways. In this way, β-cell function and mass were reduced. Together, these perturbations resulted in impaired insulin secretion, progressive hyperglycemia, and, ultimately, development of diabetes. Conclusions: Loss of Tfb2m in pancreatic β-cells results in progressive mitochondrial dysfunction. Consequently, insulin secretion in response to metabolic stimuli is impaired and β-cell mass reduced. Our findings indicate that TFB2M plays an important functional role in pancreatic β-cells. Perturbations of its actions may lead to loss of functional β-cell mass, a hallmark of T2D.
|
|
| 10. |
- Shcherbina, L, et al.
(författare)
-
Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes
- 2017
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 447, s. 52-60
-
Tidskriftsartikel (refereegranskat)abstract
- Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype.
|
|
