16 results on '"Hahn, Max"'
Search Results
2. Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
- Author
-
Chotiwan, Nunya, Rosendal, Ebba, Willekens, Stefanie M. A., Schexnaydre, Erin, Nilsson, Emma, Lindqvist, Richard, Hahn, Max, Mihai, Ionut Sebastian, Morini, Federico, Zhang, Jianguo, Ebel, Gregory D., Carlson, Lars-Anders, Henriksson, Johan, Ahlgren, Ulf, Marcellino, Daniel, and Överby, Anna K.
- Published
- 2023
- Full Text
- View/download PDF
3. Quantitative 3D OPT and LSFM datasets of pancreata from mice with streptozotocin-induced diabetes
- Author
-
Hahn, Max, Nord, Christoffer, van Krieken, Pim P., Berggren, Per-Olof, Ilegems, Erwin, Cheddad, Abbas, and Ahlgren, Ulf
- Published
- 2022
- Full Text
- View/download PDF
4. Gsα-dependent signaling is required for postnatal establishment of a functional β-cell mass
- Author
-
Serra-Navarro, Berta, Fernandez-Ruiz, Rebeca, García-Alamán, Ainhoa, Pradas-Juni, Marta, Fernandez-Rebollo, Eduardo, Esteban, Yaiza, Mir-Coll, Joan, Mathieu, Julia, Dalle, Stephane, Hahn, Max, Ahlgren, Ulf, Weinstein, Lee S., Vidal, Josep, Gomis, Ramon, and Gasa, Rosa
- Published
- 2021
- Full Text
- View/download PDF
5. ANOTHER ADDICTION
- Author
-
Hahn, Max
- Published
- 2019
6. 3D imaging of human organs with micrometer resolution - applied to the endocrine pancreas
- Author
-
Hahn, Max, Nord, Christoffer, Eriksson, Maria, Morini, Federico, Alanentalo, Tomas, Korsgren, Olle, and Ahlgren, Ulf
- Published
- 2021
- Full Text
- View/download PDF
7. An MR-based brain template and atlas for optical projection tomography and light sheet fluorescence microscopy in neuroscience.
- Author
-
Willekens, Stefanie M. A., Morini, Federico, Mediavilla, Tomas, Nilsson, Emma, Orädd, Greger, Hahn, Max, Chotiwan, Nunya, Visa, Montse, Berggren, Per-Olof, Ilegems, Erwin, Överby, Anna K., Ahlgren, Ulf, and Marcellino, Daniel
- Subjects
OPTICAL tomography ,FLUORESCENCE microscopy ,THALAMUS ,HIGH resolution imaging ,IMAGE fusion - Abstract
Introduction: Optical Projection Tomography (OPT) and light sheet fluorescence microscopy (LSFM) are high resolution optical imaging techniques, ideally suited for ex vivo 3D whole mouse brain imaging. Although they exhibit high specificity for their targets, the anatomical detail provided by tissue autofluorescence remains limited. Methods: T1-weighted images were acquired from 19 BABB or DBE cleared brains to create an MR template using serial longitudinal registration. Afterwards, fluorescent OPT and LSFM images were coregistered/normalized to the MR template to create fusion images. Results: Volumetric calculations revealed a significant difference between BABB and DBE cleared brains, leading to develop two optimized templates, with associated tissue priors and brain atlas, for BABB (OCUM) and DBE (iOCUM). By creating fusion images, we identified virus infected brain regions, mapped dopamine transporter and translocator protein expression, and traced innervation from the eye along the optic tract to the thalamus and superior colliculus using cholera toxin B. Fusion images allowed for precise anatomical identification of fluorescent signal in the detailed anatomical context provided by MR. Discussion: The possibility to anatomically map fluorescent signals on magnetic resonance (MR) images, widely used in clinical and preclinical neuroscience, would greatly benefit applications of optical imaging of mouse brain. These specific MR templates for cleared brains enable a broad range of neuroscientific applications integrating 3D optical brain imaging. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes
- Author
-
Hahn, Max, van Krieken, Pim P., Nord, Christoffer, Alanentalo, Tomas, Morini, Federico, Xiong, Yan, Eriksson, Maria, Mayer, Jürgen, Kostromina, Elena, Ruas, Jorge L., Sharpe, James, Pereira, Teresa, Berggren, Per-Olof, Ilegems, Erwin, and Ahlgren, Ulf
- Published
- 2020
- Full Text
- View/download PDF
9. Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence
- Author
-
Hahn, Max, Nord, Christoffer, Franklin, Oskar, Alanentalo, Tomas, Mettävainio, Martin Isaksson, Morini, Federico, Eriksson, Maria, Korsgren, Olle, Sund, Malin, and Ahlgren, Ulf
- Published
- 2020
- Full Text
- View/download PDF
10. The joint project SENSE – fibre-optic strain sensing with respect to a known reference
- Author
-
Krawczyk, Charlotte M., Wollin, Christopher, Ehsaninezhad, Leila, Liehr, Sascha, Kloth, Andre, Kirchner, Julia, Hahn, Max, Lipus, Martin, Hart, Johannes, Zabihi, Mohammadmasoud, Krebber, Katerina, Hicke, Konstantin, Weber, Bernd, and Reinsch, Thomas
- Abstract
For the efficient use of geothermal energy, especially for heat provision, energy must be provided close to a consumer structure, thus in urban areas. Exploration for potential reservoir or storage horizons and their microseismic monitoring during operation are, therefore, mandatory.For this purpose, the joint project SENSE tests seismic exploration and monitoring approaches based on fibre-optic sensing in urban areas using both active and passive seismic sources. To carry out the seismic measurements, a field-ready demonstrator is being built to carry out spatially distributed dynamic fibre-optic strain measurements. In addition to available instrumentation, strain changes with respect to a known reference are recorded, thereby also enabling the detection of long-term/quasi-static strain changes. This brings decisive advantages with regard to the detection of deep or long-wave signals as well as for the exclusion of very slow deformation movements in connection with the use of the geological subsurface.We exemplify the monitoring of borehole operations and the horizontal recording of the seismic wave field using cables in Berlin and Potsdam with the new developments tested. Processing workflows encompass shot gather extraction, and picking of dispersion curves that yield after inversion shear wave velocity models exposing several velocity interfaces. To this end, we expect that SENSE will deliver new options for urban monitoring also beyond geothermal., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)
- Published
- 2023
11. Tredimensionella analyser av de Langerhanska öarna vid diabetes
- Author
-
Hahn, Max
- Subjects
anatomy ,diabetes ,β-cell mass ,Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) ,fluorescence microscopy ,3D imaging ,Biomedicinsk laboratorievetenskap/teknologi ,3D image analysis ,Insulin ,Biomedical Laboratory Science/Technology ,pancreas ,technique development ,Islet of Langerhans ,Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) - 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.
- Published
- 2022
12. Distinct Opsin 3 (Opn3) Expression in the Developing Nervous System during Mammalian Embryogenesis
- Author
-
Davies, Wayne I. L., Sghari, Soufien, Upton, Brian A., Nord, Christoffer, Hahn, Max, Ahlgren, Ulf, Lang, Richard A., and Gunhaga, Lena
- Published
- 2021
- Full Text
- View/download PDF
13. Mesoscopic Optical Imaging of the Pancreas—Revisiting Pancreatic Anatomy and Pathophysiology.
- Author
-
Alanentalo, Tomas, Hahn, Max, Willekens, Stefanie M. A., and Ahlgren, Ulf
- Subjects
OPTICAL images ,PANCREAS ,OPTICAL tomography ,ANATOMY ,FLUORESCENCE microscopy - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
14. Visualisation of single heavy atoms with the electron microscope
- Author
-
Formanek, H., Müller, Martin, Hahn, Max H., and Koller, T.
- Published
- 1971
- Full Text
- View/download PDF
15. SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.
- Author
-
Hellman U, Rosendal E, Lehrstrand J, Henriksson J, Björsell T, Wennemo A, Hahn M, Österberg B, Dorofte L, Nilsson E, Forsell MNE, Smed-Sörensen A, Lange A, Karlsson MG, Ahlm C, Blomberg A, Cajander S, Ahlgren U, Lind A, Normark J, Överby AK, and Lenman A
- Subjects
- Humans, Male, Prospective Studies, Middle Aged, Female, Aged, Severity of Illness Index, Adult, COVID-19 metabolism, Hyaluronic Acid metabolism, Hyaluronic Acid blood, SARS-CoV-2, Lung pathology, Lung metabolism
- Abstract
We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS, 6-9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.IMPORTANCEThis study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies., Competing Interests: A. Lenman has received unconditional research support from Carl Bennet AB. A.S.-S. has received payments from Astra-Zeneca for Data and Safety Monitoring Board (DSMB) work on COVID-19 phase I/II/III clinical trials. S.C. has participated in DSMBs for Pfizer, Sobi, and MSD Merck. There are no patents, products in development, or marketed products associated with this research to declare. All other authors declare no conflicts of interest.
- Published
- 2024
- Full Text
- View/download PDF
16. 3D Optical Molecular Imaging of the Rodent Pancreas by OPT and LSFM.
- Author
-
Hahn M and Ahlgren U
- Subjects
- Animals, Rodentia, Pancreas diagnostic imaging, Microscopy, Fluorescence, Molecular Imaging, Imaging, Three-Dimensional methods, Tomography, Optical methods, Islets of Langerhans diagnostic imaging
- 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., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.