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Sökning: WFRF:(Ahlgren Ulf)

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3.
  • Ahlgren, Jennie, et al. (författare)
  • Consumers on the Internet : ethical and legal aspects of commercialization of personalized nutrition
  • 2013
  • Ingår i: Genes & Nutrition. - : Springer. - 1555-8932 .- 1865-3499. ; 8:4, s. 349-355
  • Forskningsöversikt (refereegranskat)abstract
    • Consumers often have a positive attitude to the option of receiving personalized nutrition advice based upon genetic testing, since the prospect of enhancing or maintaining one’s health can be perceived as empowering. Current direct-to-consumer services over the Internet, however, suffer from a questionable level of truthfulness and consumer protection, in addition to an imbalance between far-reaching promises and contrasting disclaimers. Psychological and behavioral studies indicate that consumer acceptance of a new technology is primarily explained by the end user’s rational and emotional interpretation as well as moral beliefs. Results from such studies indicate that personalized nutrition must create true value for the consumer. Also, the freedom to choose is crucial for consumer acceptance. From an ethical point of view, consumer protection is crucial, and caution must be exercised when putting nutrigenomic-based tests and advice services on the market. Current Internet offerings appear to reveal a need to further guaranty legal certainty by ensuring privacy, consumer protection and safety. Personalized nutrition services are on the borderline between nutrition and medicine. Current regulation of this area is incomplete and undergoing development. This situation entails the necessity for carefully assessing and developing existing rules that safeguard fundamental rights and data protection while taking into account the sensitivity of data, the risks posed by each step in their processing, and sufficient guarantees for consumers against potential misuse.
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5.
  • Ahlgren, Jennie, et al. (författare)
  • Ethical considerations in relation to personalised nutrition : An overview of Work Package 5, with respect to ethics
  • 2015
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The objectives of Food4Me work package 5 included a baseline assessment of the ethical and legal aspects of personalised nutrition at the start of the project in 2011, as well as a final assessment at the end of the project (2015), taking into account results achieved in other work packages. The initial assessment made a number of ethical issues visible, most of them relating to the consumer of personalised nutrition service. The results depicted in this publication indicate that many of the questions raised in relation to these issues remain unsolved, and in some cases they seem to be neglected in relation to the services offered by internet companies.
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6.
  • Ahlgren, Jennie, et al. (författare)
  • Ska generna styra vad vi äter?
  • 2008
  • Ingår i: Miljöforskning: Formas tidning för ett uthålligt samhälle. ; :3
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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7.
  • Ahlgren, Jennie, 1978-, et al. (författare)
  • Ska generna styra vad vi äter?
  • 2005
  • Ingår i: Miljöforskning. ; :3
  • Tidskriftsartikel (populärvet., debatt m.m.)
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8.
  • Ahlgren, Jennie, et al. (författare)
  • Ska generna styra vad vi äter?
  • 2005
  • Ingår i: Miljöforskning : Formas tidning för ett uthålligt samhälle. - 1650-4925. ; 2005:3, s. 16-17
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • This article gives an overview of some ethical problems raised in connection to nutritional genomics, especially the use of knowledge from nutrigenomics as a basis for personalised nutrition after a genetic test.
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12.
  • Ahlgren, Ulf, et al. (författare)
  • Approaches for imaging islets
  • 2010
  • Ingår i: Advances in Experimental Medicine and Biology. - Dordrecht : Springer Netherlands. - 0065-2598 .- 2214-8019. ; 654, s. 39-57
  • Tidskriftsartikel (refereegranskat)abstract
    • The establishment of improved technologies for imaging of the pancreas is a key element in addressing several aspects of diabetes pathogenesis. In this respect, the development of a protocol that allows for non-invasive scoring of human islets, or islet beta-cells, is of particular importance. The development of such a technology would have profound impact on both clinical and experimental medicine, ranging from early diagnosis of diabetes to the evaluation of therapeutic regimes. Another important task is the development of modalities for high-resolution imaging of experimental animal models for diabetes. Rodent models for diabetes research have for decades been instrumental to the diabetes research community. The ability to image, and to accurately quantify, key players of diabetogenic processes with molecular specificity will be of great importance for elucidating mechanistic aspects of the disease. This chapter aims to overview current progress within these research areas.
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15.
  • Ahlgren, Ulf, et al. (författare)
  • Imaging the pancreatic beta cell : chapter 13
  • 2011
  • Ingår i: Type 1 diabetes. - : InTech. - 9789533073620
  • Bokkapitel (refereegranskat)abstract
    • This book is a compilation of reviews about the pathogenesis of Type 1 Diabetes. T1D is a classic autoimmune disease. Genetic factors are clearly determinant but cannot explain the rapid, even overwhelming expanse of this disease. Understanding etiology and pathogenesis of this disease is essential. A number of experts in the field have covered a range of topics for consideration that are applicable to researcher and clinician alike. This book provides apt descriptions of cutting edge technologies and applications in the ever going search for treatments and cure for diabetes. Areas including T cell development, innate immune responses, imaging of pancreata, potential viral initiators, etc. are considered.
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16.
  • Ahlgren, Ulf, et al. (författare)
  • Optical imaging of islets : new possibilities by the development of infrared fluorescent proteins
  • 2009
  • Ingår i: Islets. - : Informa UK Limited. - 1938-2022 .- 1938-2014. ; 1:2, s. 163-164
  • Tidskriftsartikel (refereegranskat)abstract
    • The capacity to record the spatial and quantitative distribution of cellular subtypes involved in diabetogenic processes is a key element in experimental diabetes research. A non-invasive technique to accurately monitor parameters such as pancreatic β-cell mass (BCM) and its distribution would provide a stepping stone in understanding different aspects of diabetes pathogenesis. It would also assist in the development of therapeutic regimes by providing a tool for the evaluation of anti-diabetic drugs or other curative or diagnostic measures. At present, a range of imaging modalities are being explored for this purpose. Whereas nuclear imaging techniques, characterised by their high tissue penetration depth but relatively low spatial resolution, appear most promising for the study of humans and large animals, optical imaging enables a route to cost-effective, high sensitivity, high resolution imaging in rodent models for disease. In this commentary, the potential impact of infrared fluorescent proteins (IFPs), as recently reported by Shu et al in Science, for imaging of the pancreas in small animals will be discussed.
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17.
  • Alanentalo, Tomas, et al. (författare)
  • High-resolution three-dimensional imaging of islet-infiltrate interactions based on optical projection tomography assessments of the intact adult mouse pancreas
  • 2008
  • Ingår i: Journal of Biomedical Optics. - Bellingham, WA : SPIE--the International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 13:5, s. 054070-
  • Tidskriftsartikel (refereegranskat)abstract
    • A predicament when assessing the mechanisms underlying the pathogenesis of type-1 diabetes (T1D) has been to maintain simultaneous global and regional information on the loss of insulin-cell mass and the progression of insulitis. We present a procedure for high-resolution 3-D analyses of regions of interest (ROIs), defined on the basis of global assessments of the 3-D distribution, size, and shape of molecularly labeled structures within the full volume of the intact mouse pancreas. We apply a refined protocol for optical projection tomography (OPT)-aided whole pancreas imaging in combination with confocal laser scanning microscopy of site-directed pancreatic microbiopsies. As such, the methodology provides a useful tool for detailed cellular and molecular assessments of the autoimmune insulitis in T1D. It is anticipated that the same approach could be applied to other areas of research where 3-D molecular distributions of both global and regional character is required.
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18.
  • Alanentalo, Tomas, et al. (författare)
  • Mesoscopic Optical Imaging of the Pancreas : Revisiting Pancreatic Anatomy and Pathophysiology
  • 2021
  • Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
  • Forskningsöversikt (refereegranskat)abstract
    • The exocrine-endocrine multipart organization of the pancreas makes it an exceedingly challenging organ to analyze, quantitatively and spatially. Both in rodents and humans, estimates of the pancreatic cellular composition, including beta-cell mass, has been largely relying on the extrapolation of 2D stereological data originating from limited sample volumes. Alternatively, they have been obtained by low resolution non-invasive imaging techniques providing little detail regarding the anatomical organization of the pancreas and its cellular and/or molecular make up. In this mini-review, the state of the art and the future potential of currently existing and emerging high-resolution optical imaging techniques working in the mm-cm range with μm resolution, here referred to as mesoscopic imaging approaches, will be discussed regarding their contribution toward a better understanding of pancreatic anatomy both in normal conditions and in the diabetic setting. In particular, optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) imaging of the pancreas and their associated tissue processing and computational analysis protocols will be discussed in the light of their current capabilities and future potential to obtain more detailed 3D-spatial, quantitative, and molecular information of the pancreas.
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19.
  • Alanentalo, Tomas, 1978- (författare)
  • Optical projection tomography based 3D-spatial and quantitative assessments of the diabetic pancreas
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The gastrointestinal tract comprises a number of digestive organs including the stomach and pancreas. The stomach is involved in the digestion and short term storage of food while the pancreas is a mixed endocrine and exocrine gland which provides the body with hormones and enzymes essential for nutritional utilisation. The pancreas consists of three different cell lineages, acinar, ductal and endocrine cells. The endocrine cells, organised in the islets of Langerhans, are scattered throughout the exocrine parenchyma and regulate blood glucose levels by production of hormones such as glucagon and insulin. The Nkx family of homeodomain proteins controls numerous processes during development. Previous studies have identified two members belonging to the Nkx6 subfamily of Nkx proteins, Nkx6.1 and Nkx6.2. We have described the cloning and embryonic expression pattern of Nkx6.3. All three members of the Nkx6 gene family were shown to be expressed in partially overlapping domains during the development of the gastrointestinal tract and the central nervous system. Nkx6.2 was also identified as a transient marker for pancreatic exocrine cells. Analysing gene expression patterns and morphological features in tissues and organs is often performed by stereologic sampling which is a labour-intensive two dimensional approach that rely on certain assumptions when calculating e.g. β-cell mass and islet number in the pancreas. By combined improvements in immunohistochemical protocols, computational processing and tomographic scanning, we have developed a methodology based on optical projection tomography (OPT) allowing for 3D visualisation and quantification of specifically labelled objects within intact adult mouse organs. In the pancreas, this technique allows for spatial and quantitative measurements of total islet number and β-cell mass. We have further developed a protocol allowing for high resolution regional analyses based on global OPT assessments of the pancreatic constitution. This methodology is likely to facilitate detailed cellular and molecular analysis of user defined regions of interest in the pancreas, at the same time providing information on the overall disease state of the gland. Type 1 diabetes mellitus (T1D) can occur at any age and is characterized by the marked inability of the pancreas to secrete insulin due to an autoimmune destruction of the insulin producing β-cells. Information on the key cellular and molecular events underlying the recruitment of lymphocytes, their infiltration of the islets of Langerhans and consequent β-cell destruction is essential for understanding the pathogenesis of T1D. Using the developed methodology we have recorded the spatial and quantitative distribution of islet β-cells and infiltrating lymphocytes in the non obese diabetic (NOD) mouse model for T1D. This study shows that the smaller islets, which are predominantly organised in the periphery of the organ, are the first to disappear during the progression of T1D. The larger islets appear more resistant and our data suggest that a compensatory proliferative process is going on side by side with the autoimmune-induced β-cell destruction. Further, the formation of structures resembling tertiary lymphoid organs (TLOs) in areas apparently unaffected by insulitis suggests that local factors may provide cues for the homing of these lymphocytes back to the pancreas.
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20.
  • Alanentalo, Tomas, et al. (författare)
  • Quantification and 3-D imaging of the insulitis-induced destruction of β-cells in murine type 1 diabetes
  • 2010
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:7, s. 1756-1764
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the NOD mouse model of the disease.Research design and methods: Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the 3D spatial development and progression of insulitis and beta-cell destruction in pancreas from diabetes prone NOD and non-diabetes prone congenic NOD.H-2b mice between 3 and 16 weeks of age.Results: Together with results showing the spatial dynamics of the insulitis process we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression.Conclusions: Our data provides a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.
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22.
  • Albin, Maria, et al. (författare)
  • Cytogenetic and morphologic subgroups of myelodysplastic syndromes in relation to occupational and hobby exposures.
  • 2003
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 29:5, s. 378-387
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This study investigated the association between occupational and hobby exposure and the risk of myelodysplastic syndromes (MDS) while focusing on differential patterns of clonal chromosome aberrations and morphologic subgroups. METHODS: A case-referent study was conducted with 330 MDS patients investigated cytogenetically in 1976-1993 (cases) and matched referents. Telephone interviews with either the person or a next-of-kin were used. The participation rate of the cases and referents was 85% and 60%, respectively. Information was obtained from the next-of-kin more often for the cases (88%) than for the referents (26%). Occupational hygienists assessed the exposure using interview data on worktasks and hobbies. Associations with disease risk were evaluated for 10 exposures with a logistic regression analysis. RESULTS: The investigated exposures were generally not associated with cytogenetically abnormal MDS. Effect estimates for specific cytogenetic or morphologic subgroups were generally imprecise. Occupational exposure to extremely low-frequency magnetic fields (EMF) was associated with MDS with a normal karyotype [odds ratio (OR) 2.0, 95% confidence interval (95% CI) 1.0-4.0]. The exposure-response association was consistent for intensity but inconclusive for duration. A decreased risk was observed for MDS, irrespective of karyotypic pattern, among farmers and farmhands (OR 0.53, 95% CI 0.35-0.81). CONCLUSIONS: Cytogenetically abnormal MDS was generally not associated with occupational or hobby exposure to known or suspected genotoxic agents. However, exposure prevalences and intensities were low for several agents. An association was suggested between occupational exposure to EMF and MDS with a normal karyotype. Biases due to differential information quality and selective participation cannot be ruled out.
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  • Asayesh, Amir, et al. (författare)
  • Spleen versus pancreas : strict control of organ interrelationship revealed by analyses of Bapx1-/- mice.
  • 2006
  • Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 20:16, s. 2208-2213
  • Tidskriftsartikel (refereegranskat)abstract
    • During early stages of pancreatic development, the mesenchyme that contributes to the spleen overlies the dorsal pancreatic endoderm. Here, we show that interactions between splenic mesenchyme and pancreas proceed via a highly orchestrated morphogenetic program. Disruption of morphogenesis, as occurs in the Bapx1(Nkx3.2)−/− embryo, results in transformation of these tissues into well-organized, ectopic gut-like structures. Bapx1 plays a crucial organizing role effecting position and separation of the spleen and pancreas to prevent this metaplastic transformation. Similar transformations occur in organ cultures employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the developmental plasticity of the pancreas and that precise spatial and temporal control of tissue interactions are required for development of both organs.
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25.
  • Asayesh, Amir, 1977- (författare)
  • Spleno-pancreatic development assessed by 3D molecular imaging
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The development of different organs and tissues along the gastrointestinal tract, including the pancreas, depends on signalling between the endoderm and the adjacent mesenchyme. The Nkx gene Bapx1 is involved in spatial control of organ-positioning in the spleno-pancreatic region, and deficiency in this gene results in unacceptable proximity of the splenic mesenchyme to the pancreas. This permits agitating signals from the splenic mesenchyme to induce an in vivo (and in vitro) transformation of pancreatic epithelium to a cystic structure with gut like features. Also, wild type splenic mesenchyme is competent to induce a similar transformation. These findings illustrate the importance for strict control of organ positioning during spleno-pancreatic development. Several growth factors and receptors involved in pancreatic development are activated by protease processing. Some of these growth factors have been implicated as substrates for members of the A Disintegrin And Metalloprotease (ADAM) family. The ADAMs 9, 10, and 17 are expressed during pancreatic development and in the adult pancreas, suggesting a possible role for these ADAMs in pancreatic development and function. Animal model systems are widely used to investigate gene function during development and disease. However, spatial, molecular, and quantitative phenotype screening in animals is a time consuming effort. Optical Projection Tomography is a 3-dimensional imaging technique that, in combination with improvements in sample preparation and computer processing, can be used to visualize and quantify characteristics of intact adult mouse organs such as the total β-cell content in the pancreas.
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26.
  • Baeyens, Luc, et al. (författare)
  • Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice
  • 2014
  • Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 32:1, s. 76-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification.
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27.
  • Björk, Jonas, et al. (författare)
  • Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?
  • 2001
  • Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 58:11, s. 722-727
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.
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28.
  • Cheddad, Abbas, 1975-, et al. (författare)
  • Image processing assisted algorithms for optical projection tomography
  • 2012
  • Ingår i: IEEE Transactions on Medical Imaging. - 0278-0062 .- 1558-254X. ; 31:1, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Since it was first presented in 2002, optical projection tomography (OPT) has emerged as a powerful tool for the study of biomedical specimen on the mm to cm scale. In this paper, we present computational tools to further improve OPT image acquisition and tomographic reconstruction. More specifically, these methods provide: semi-automatic and precise positioning of a sample at the axis of rotation and a fast and robust algorithm for determination of postalignment values throughout the specimen as compared to existing methods. These tools are easily integrated for use with current commercial OPT scanners and should also be possible to implement in "home made" or experimental setups for OPT imaging. They generally contribute to increase acquisition speed and quality of OPT data and thereby significantly simplify and improve a number of three-dimensional and quantitative OPT based assessments.
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29.
  • Cheddad, Abbas, et al. (författare)
  • Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion
  • 2013
  • Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 21:14, s. 16584-16604
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods.
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30.
  • Chotiwan, Nunya, et al. (författare)
  • Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Viral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combine multimodal imaging (cm-nm scale) with single nuclei RNA-sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar-/-) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection is imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection is limited to grey matter of sensory systems in wildtype mice, but extends into white matter, meninges and choroid plexus in Ifnar-/- mice. Cells in wildtype display strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+ NK cells, whereas in Ifnar-/-, the absence of this response contributes to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.
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31.
  • Davies, Wayne I. L., et al. (författare)
  • Distinct opsin 3 (Opn3) expression in the developing nervous system during mammalian embryogenesis
  • 2021
  • Ingår i: eNeuro. - : Society for Neuroscience. - 2373-2822. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Opsin 3 (Opn3) is highly expressed in the adult brain, however, information for spatial and temporal expression patterns during embryogenesis is significantly lacking. Here, an Opn3-eGFP reporter mouse line was used to monitor cell body expression and axonal projections during embryonic and early postnatal to adult stages. By applying 2D and 3D fluorescence imaging techniques, we have identified the onset of Opn3 expression, which predominantly occurred during embryonic stages, in various structures during brain/head development. In ad-dition, this study defines over twenty Opn3-eGFP-positive neural structures never reported before. Opn3-eGFP was first observed at E9.5 in neural regions, including the ganglia that will ultimately form the trigeminal, facial and vestibulocochlear cranial nerves (CNs). As development proceeds, expanded Opn3-eGFP expression coincided with the formation and maturation of critical components of the central and peripheral nervous systems (CNS, PNS), including various motor-sensory tracts, such as the dorsal column-medial lemniscus (DCML) sensory tract, and olfactory, acoustic, and optic tracts. The widespread, yet distinct, detection of Opn3-eGFP already at early embryonic stages suggests that Opn3 might play important functional roles in the developing brain and spinal cord to regulate multiple motor and sensory circuitry systems, including proprio-ception, nociception, ocular movement, and olfaction, as well as memory, mood, and emotion. This study presents a crucial blueprint from which to investigate autonomic and cognitive opsin-dependent neural development and resultant behaviors under physiological and pathophysiological conditions.
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32.
  • Eriksson, Anna U., et al. (författare)
  • Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research
  • 2013
  • Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; 71
  • Tidskriftsartikel (refereegranskat)abstract
    • By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.
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33.
  • Eriksson, Maria, et al. (författare)
  • Insulin-Binding Peptide Probes Provide a Novel Strategy for Pancreatic β-Cell Imaging
  • 2021
  • Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 18:12, s. 4428-4436
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes develops in childhood and adolescence, with peak incidence in the early teenage years. There is an urgent need for an accurate method to detect insulin-producing β-cells in patients that is not affected by alterations in β-cell function. As part of our research program to design specific probes to measure β-cell mass, we recently developed a novel insulin-binding peptide probe (IBPP) for the detection of β-cells in vivo. Here, we applied our innovative method to show specific labeling of this IBPP to human and mouse fixed β-cells in pancreatic islets. Importantly, we showed staining of human and mouse islets in culture without any negative functional or cell viability impact. Moreover, the IBPP-stained mouse islets after tail vein injection in vivo, albeit with batch differences in staining efficiency. In conclusion, we provide evidence showing that the IBPP can be used for future accurate detection of β-cell mass in a variety of preclinical models of diabetes.
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34.
  • Eter, Wael A., et al. (författare)
  • SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for beta-cell mass assessments
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in beta-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total beta-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate beta-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of beta-cells. Uptake of a promising radiotracer for beta-cell imaging by SPECT, In-111-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of In-111-exendin-3 and insulin positive beta-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of beta-cell radiotracers.
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35.
  • Grong, Eivind, et al. (författare)
  • Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography
  • 2016
  • Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 30:2, s. 532-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.Methods Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.Results Body weight did not differ between groups (Pg = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (Pg = 0.037); HbA1c levels in SG were lower compared to DJ only (p\0.05). GLP-1 levels were elevated for DJ compared to SG and sham (Pg = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (Pg = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).Conclusion Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.
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36.
  • Grong, E., et al. (författare)
  • The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats
  • 2018
  • Ingår i: Journal of Endocrinological Investigation. - : Springer. - 0391-4097 .- 1720-8386. ; 41:6, s. 691-701
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals.Methods: Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle + sham operation (GK-V). Body weight, glucose parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified by optical projection tomography.Results: After surgery, body weight development was equal among groups (Pg = 0.75). Fasting and stimulated gastrin increased for GK-PPI and GK-SG vs. GK-V (p < 0.05 for all). Fasting blood glucose was decreased for GK-PPI and GK-SG vs. GK-V (p < 0.05 and p = 0.052). HbA1c was lower for GK-SG vs. GK-V at 6 weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks postoperative (p < 0.05 for all); a borderline difference was observed for GK-SG vs. GK-V at 18 weeks (p = 0.054). Total- and LDL cholesterol was elevated for GK-PPI compared to the other two groups (p < 0.05 for all). Beta-cell mass did not differ among groups (p = 0.35).Conclusions: Hypergastrinemia following sleeve gastrectomy and pantoprazole has a similar, modest effect on glycemic control in Goto-Kakizaki rats but does not enhance beta-cell mass after 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.
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37.
  • Gurzov, Esteban N., et al. (författare)
  • Novel Strategies to Protect and Visualize Pancreatic beta Cells in Diabetes
  • 2020
  • Ingår i: Trends in endocrinology and metabolism. - : Elsevier. - 1043-2760 .- 1879-3061. ; 31:12, s. 905-917
  • Forskningsöversikt (refereegranskat)abstract
    • A common feature in the pathophysiology of different types of diabetes is the reduction of beta cell mass and/or impairment of beta cell function. Diagnosis and treatment of type 1 and type 2 diabetes is currently hampered by a lack of reliable techniques to restore beta cell survival, to improve insulin secretion, and to quantify beta cell mass in patients. Current new approaches may allow us to precisely and specifically visualize beta cells in vivo and provide viable therapeutic strategies to preserve, recover, and regenerate beta cells. In this review, we discuss recent protective approaches for beta cells and the advantages and limitations of current imaging probes in the field.
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38.
  • Görman, Ulf, et al. (författare)
  • Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition
  • 2013
  • Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 8:4, s. 373-381
  • Forskningsöversikt (refereegranskat)abstract
    • This article discusses the prospects and limitations of the scientific basis for offering personalized nutrition advice based upon individual genetic information. Two divergent scientific positions are presented, with an ethical comment. The crucial question is whether the current knowledge base is sufficiently strong for taking an ethically responsible decision to offer personalized nutrition advice based upon gene–diet–health interaction. According to the first position, the evidence base for translating the outcomes of nutrigenomics research into personalized nutritional advice is as yet immature. There is also limited evidence that genotype-based dietary advice will motivate appropriate behavior changes. Filling the gaps in our knowledge will require larger and better randomized controlled trials. According to the second position, personalized nutrition must be evaluated in relation to generally accepted standard dietary advice—partly derived from epidemiological observations and usually not proven by clinical trials. With personalized nutrition, we cannot demand stronger evidence. In several specific cases of gene–diet interaction, it may be more beneficial for individuals with specific genotypes to follow personalized advice rather than general dietary recommendations. The ethical comment, finally, considers the ethical aspects of deciding how to proceed in the face of such uncertainty. Two approaches for an ethically responsible way forward are proposed. Arguing from a precautionary approach, it is suggested that personalized dietary advice should be offered only when there is strong scientific evidence for health effects, followed by stepwise evaluation of unforeseen behavioral and psychological effects. Arguing from theoretical and applied ethics as well as psychology, it is also suggested that personalized advice should avoid paternalism and instead focus on supporting the autonomous choice of each person.
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39.
  • Görman, Ulf, et al. (författare)
  • Ethical Considerations in Nutrigenetics and Nutrigenomics
  • 2020
  • Ingår i: Principles of Nutrigenetics and Nutrigenomics : Fundamentals for Individualized Nutrition - Fundamentals for Individualized Nutrition. - London : Elsevier. - 9780128045725 - 9780128045879 ; , s. 543-548
  • Bokkapitel (refereegranskat)abstract
    • Ethics is the study of the normative dimensions of human relations and experiences. This chapter discusses such questions in relation to basic values in modern society. The normative foundations for the analysis are the values of human dignity, autonomy, freedom, equality, and solidarity, as well as the responsibilities of society toward its citizens, including freedom, security, and justice. The questions that are brought up touch on how implementing nutrigenetics and nutrigenomics in personalized nutrition services relates to these values.Health and food are primary human needs. The choice of food can contribute to the support of health, but it can also come into conflict with health. Personalized nutrition may be seen as part of a wider trend toward early preventive actions to treat susceptibility to disease. If personalization of nutrition can contribute to eating habits that support health instead of threatening it, this will be beneficial for the individual, but it may also be good for society as a whole. As a consequence, pressure on societal expenses for health care may be reduced.Personalized nutrition, as well as the wider concept of precision nutrition, have stimulated expectations and are often described as having great potential, but it has also been difficult to realize them. Studies indicate that there is widespread optimism among researchers engaged in nutrigenetics and nutrigenomics regarding at least its long-term benefits, whereas there are divergent viewpoints within the wider research community. In this situation, ethical concerns need to receive attention.
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40.
  • Hahn, Max, et al. (författare)
  • 3D imaging of human organs with micrometer resolution - applied to the endocrine pancreas
  • 2021
  • Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The possibility to quantitatively study specific molecular/cellular features of complete human organs with preserved spatial 3D context would have widespread implications for pre-clinical and clinical medicine. Whereas optical 3D imaging approaches have experienced a formidable revolution, they have remained limited due to current incapacities in obtaining specific labelling within large tissue volumes. We present a simple approach enabling reconstruction of antibody labeled cells within entire human organs with preserved organ context. We demonstrate the utility of the approach by providing volumetric data and 3D distribution of hundreds of thousands of islets of Langerhans within the human pancreas. By assessments of pancreata from non-diabetic and type 2 diabetic individuals, we display previously unrecognized features of the human islet mass distribution and pathology. As such, this method may contribute not only in unraveling new information of the pancreatic anatomy/pathophysiology, but it may be translated to essentially any antibody marker or organ system.
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41.
  • Hahn, Max, 1993-, et al. (författare)
  • 3D optical molecular imaging of the rodent pancreas by OPT and LSFM
  • 2023
  • Ingår i: Type-1 diabetes. - New York : Humana Press. - 9781071628065 - 9781071628096 - 9781071628072 ; , s. 1-19
  • Bokkapitel (refereegranskat)abstract
    • The rodent pancreas is the prevalent model system for preclinical diabetes research. However, due to the compound endocrine–exocrine organization of the gland, with the endocrine islets of Langerhans scattered by the thousands throughout the much greater exocrine parenchyma, stereological assessments of endocrine cell mass, commonly insulin-producing ß-cells, are exceedingly challenging. In recent years, optical mesoscopic imaging techniques such as optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) have seen dramatic developments, enabling 3D visualization of fluorescently labeled cells in mm- to cm-sized tissues with μm resolution. Here we present a protocol for 3D visualization and “absolute” quantitative assessments of, for example, islet mass throughout the volume of rodent pancreata with maintained spatial context.
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42.
  • Hahn, Max, 1993- (författare)
  • Characterizing the pancreatic "isletome" : 3D optical imaging to study diabetes
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The pancreas is a specialised multipurpose organ, that can be separated into two major compartments: endocrine and exocrine. The exocrine part makes up the majority of the organ volume and functions to secrete digestive enzymes into the small intestine. Notably, endocrine islets of Langerhans are embedded and scattered in vast numbers throughout the exocrine space. These miniature functional units are composed of different cell types that secrete hormones into the blood stream. The most abundant islet-cell is the insulin-producing β-cell. Highly coordinated, the endocrine cells are the primary regulators of energy homeostasis in the body. Together, the collective islet volume constitutes the pancreatic “isletome”, a synchronised, complex and size-equilibrated system that is able to respond to various metabolic conditions. Indeed, environmental and/or genetic conditions often lead to impaired islet function and/or β-cell destruction leading to elevated blood glucose levels over time and eventually diabetes. Diabetes mellitus is a disease that currently affects more than 400 million individuals worldwide. As such, understanding pancreatic disease-related mechanisms is pivotal to the development of new and more effective therapeutic, or even curative, regimens. The deep location of the pancreas in the abdomen and the relatively low resolution of current clinical imaging approaches, however, render the pancreatic islets difficult to study when visually assessing endocrine function. Although non-invasive imaging techniques have yet to reach their full potential, post-mortem studies of the pancreas and rodent disease models offer unique insights into the process of diabetes disease dynamics.Diabetes induced by streptozotocin (STZ) is a widely used model system in pre-clinical research, where it is generally believed that the b-cells are depleted upon the administration of the drug. Yet, quantification of β-cell volume dynamics and underlying disease mechanisms have not been extensively described. Using optical projection tomography (OPT), light sheet fluorescence microscopy (LSFM) and advanced protocols for ex vivo whole organ three-dimensional (3D) imaging, this study demonstrated that STZ-induced β-cell depletion is modest, primarily affecting large islets, and is not the primary cause for the development of diabetes in STZ-diabetic mice. Combined with islet gene expression studies, the remaining β-cell volume in STZ-diabetic mice displayed a downregulation of glucose transporter type 2 (GLUT2), a transmembrane carrier vital for sensing blood glucose levels. Islet transplantation into the anterior chamber of the eye (ACE) reversed the STZ-induced hyperglycaemia and partially restored islet function, including GLUT2, but did not restore β-cell volume loss. Extensive 3D image datasets were generated as a resource to the research community. The combined results of this study indicated that STZ-induced hyperglycaemia is not caused by β-cell loss, but rather by dysfunctional β-cells and that recovery of islet function is restrained by continuous hyperglycaemia.3D imaging using OPT has proven to be a reliable technique in quantifying cellular/anatomical features of the mouse pancreas. However, the technique has rarely been applied to patient-derived tissues. Here, a label-free and non-destructive method was developed to assess clinical biopsies within hours of collection. Specifically, this study showed that autofluorescence-based imaging can be used to delineate tumours of the pancreas (pancreatic ductal adenocarcinoma, PDAC) in 3D, which may aid in identifying tumour margins in conjunction with resective surgery. Importantly, the protocol included a reversal pipeline so that other histological workflows could be applied to the same specimen. Furthermore, this study demonstrated that natural fluorescent substances in the endocrine cells provide sufficient contrast when quantifying both the volume and number of islets of Langerhans in the healthy pancreas. Altogether, the developed technique may provide a novel tool for the rapid 3D analysis of pancreatic biopsies that may complement and improve traditional pathological assessments.With the emergence of islet transplantation networks worldwide, access to fixed pancreatic tissues from diseased donors has dramatically improved. Hereby, the near instant autolysis of the pancreas post-mortem can generally be avoided, which provides the opportunity to quantitatively study the entire gland ex vivo within a conserved spatial context. Yet, mesoscopic 3D imaging of the pancreas (by OPT and/or LSFM) has been limited predominantly due to the obstacle of labelling larger tissue volumes. As such, a simple approach to antibody labelling and cellular imaging was developed in cubic centimetre-sized tissue cuboids that were mapped to the whole organ. By stitching the resultant datasets back into 3D space, this approach demonstrated how essentially any human organ may be analysed in full with high resolution. This technique was applied to pancreata from non-diabetic and type 2 diabetic (T2D) donors, analysing over 200 thousand islets, revealing features of the human pancreas that were not analysed in 3D previously, including high islet dense regions and intra-islet haemorrhaging. Crucially, this new technique may contribute to unveil a wealth of new insights into the complex pathophysiology of the “diabetic pancreas”.By applying the above method to the entire volume of the human pancreas, the absolute distribution and volume of insulin-positive cells in a pancreas from a donor with longstanding type 1 diabetes (T1D) was demonstrated for the first time. By dividing the 19 cm long organ into smaller pieces, followed by insulin labelling, OPT imaging and reconstruction in 3D space, approximately 173,000 insulin-positive objects were identified. By utilising tissue autofluorescence, the entire organ was reconstructed in 3D, together with blood vessels and ducts. These data indicated several important regional differences in β-cell mass, such as the uncinate process showing the highest density, which potentially reflects key aspects of disease dynamics. Furthermore, regions with a “punctated distribution” of single β-cells in close proximity to each other were identified. Although the significance of these observations needs to be elucidated, we speculate that these regions could be associated with pancreatic regeneration, which might permit the development of new interventions for clinical regenerative processes in the future. Altogether, this study represents the first whole organ account of β-cell distribution at the current level of resolution in an entire organ. As such, it may serve as an important advancement towards detailed whole organ analyses of endocrine cell identity/function, via a wide range of markers, in the study of normal anatomy and pathophysiology of the human pancreas.
  •  
43.
  • Hahn, Max, et al. (författare)
  • Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence
  • 2020
  • Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • The possibility to assess pancreatic anatomy with microscopic resolution in three dimensions (3D) would significantly add to pathological analyses of disease processes. Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis with over 90% of the patients dying within 5 years after diagnosis. Cure can be achieved by surgical resection, but the efficiency remains drearily low. Here we demonstrate a method that without prior immunohistochemical labelling provides insight into the 3D microenvironment and spread of PDAC and premalignant cysts in intact surgical biopsies. The method is based solely on the autofluorescent properties of the investigated tissues using optical projection tomography and/or light-sheet fluorescence microscopy. It does not interfere with subsequent histopathological analysis and may facilitate identification of tumor-free resection margins within hours. We further demonstrate how the developed approach can be used to assess individual volumes and numbers of the islets of Langerhans in unprecedently large biopsies of human pancreatic tissue, thus providing a new means by which remaining islet mass may be assessed in settings of diabetes. Generally, the method may provide a fast approach to provide new anatomical insight into pancreatic pathophysiology.
  •  
44.
  • Hahn, Max, et al. (författare)
  • Quantitative 3D OPT and LSFM datasets of pancreata from mice with streptozotocin-induced diabetes
  • 2022
  • Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Mouse models for streptozotocin (STZ) induced diabetes probably represent the most widely used systems for preclinical diabetes research, owing to the compound's toxic effect on pancreatic beta-cells. However, a comprehensive view of pancreatic beta-cell mass distribution subject to STZ administration is lacking. Previous assessments have largely relied on the extrapolation of stereological sections, which provide limited 3D-spatial and quantitative information. This data descriptor presents multiple ex vivo tomographic optical image datasets of the full beta-cell mass distribution in mice subject to single high and multiple low doses of STZ administration, and in glycaemia recovered mice. The data further include information about structural features, such as individual islet beta-cell volumes, spatial coordinates, and shape as well as signal intensities for both insulin and GLUT2. Together, they provide the most comprehensive anatomical record of the effects of STZ administration on the islet of Langerhans in mice. As such, this data descriptor may serve as reference material to facilitate the planning, use and (re)interpretation of this widely used disease model.
  •  
45.
  • Hahn, Max, et al. (författare)
  • Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes
  • 2020
  • Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Mouse models of Streptozotocin (STZ) induced diabetes represent the most widely used preclinical diabetes research systems. We applied state of the art optical imaging schemes, spanning from single islet resolution to the whole organ, providing a first longitudinal, 3D-spatial and quantitative account of β-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced β-cell destruction predominantly affects large islets in the pancreatic core. Further, we show that hyperglycemic STZ-treated mice still harbor a large pool of remaining β-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired β-cell maturity. Reversing hyperglycemia by islet transplantation partially restored the expression of markers for islet function, but not BCM. Jointly our results indicate that STZ-induced hyperglycemia results from β-cell dysfunction rather than β-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.
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46.
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47.
  • Hallström, Elinor, et al. (författare)
  • Dietary environmental impacts relative to planetary boundaries for six environmental indicators – A population-based study
  • 2022
  • Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 373
  • Tidskriftsartikel (refereegranskat)abstract
    • The environmental impact of Swedish diets was assessed for six indicators (greenhouse gas [GHG] emissions, cropland use, nitrogen application, phosphorus application, consumptive water use and extinction rate), using self-reported food intake within two population-based cohorts of men and women, 56–96 years of age. The dietary environmental impact was assessed in relation to per capita planetary boundaries, overall and by population subgroups, addressing the relative importance of specific foods and food groups. The total average dietary impact exceeded the planetary boundaries by 1.6 to 4-fold for five of the six environmental indicators; consumptive water use did not exceed the boundaries. Comparing the highest with lowest quintiles of the population impact showed >2.5-fold differences across all environmental indicators. Of the diet's total average environmental impact, animal-based, plant-based and discretionary foods accounted for 28–83%, 8–40% and 9–37%, respectively, across the six indicators. Animal-based foods dominated the impact on GHG emissions, cropland use and nitrogen and phosphorus application, while plant-based and discretionary foods contributed more to consumptive water use and extinction rate. Environmental impact was driven predominantly by consumption of red meat, dairy, fresh fruit and coffee. The findings show major challenges in affluent countries that have to be addressed to achieving sustainable food production systems and diets. They provide guidance on critical food groups, environmental indicators and population subgroups to prioritize in future efforts to reduce the environmental impact. © 2022 The Authors
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