286 research outputs found
Morphology, biochemistry and pathophysiology of MENX-related pheochromocytoma recapitulate the clinical features.
No full textPheochromocytomas (PCCs) are tumors arising from neural crest-derived chromaffin cells. There are currently few animal models of PCC that recapitulate the key features of human tumors. Since such models may be useful for investigations of molecular pathomechanisms and development of novel therapeutic interventions, we characterized a spontaneous animal model (MENX rats) that develops endogenous PCCs with complete penetrance. Urine was longitudinally collected from wild-type (wt) and MENX-affected (mutant) rats and outputs of catecholamines and their O-methylated metabolites determined by mass spectrometry. Adrenal catecholamine contents, cellular ultrastructure and expression of phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine, were also determined in wt and mutant rats. Blood pressure was longitudinally measured and end-organ pathology assessed. Compared to wt rats, mutant animals showed age-dependent increases in urinary outputs of norepinephrine (P=0.0079) and normetanephrine (P=0.0014) that correlated in time with development of tumor nodules, increases in blood pressure and development of hypertension-related end-organ pathology. Development of tumor nodules, which lacked expression of PNMT, occurred on a background of adrenal medullary morphological and biochemical changes occurring as early as 1 month of age and involving increased adrenal medullary concentrations of dense cored vesicles, tissue contents of both norepinephrine and epinephrine and urinary outputs of metanephrine, the metabolite of epinephrine. Taken together, MENX-affected rats share several biochemical and pathophysiological features with PCC patients. This model thus provides a suitable platform to study the pathogenesis of PCC for preclinical translational studies aimed at development of novel therapies for aggressive forms of human tumors
P65. Prediction of metastases and local tumor invasion in pancreatic cancer using an orthotopic SCID mouse model
No full textAuthor Commentary: Mobile Music Technology: From Innovation to Ubiquitous Use
No full textThis author commentary chapter accompanies the re-publication of my co-authored 2006 paper ‘Mobile Music Technology: Report on an Emerging Community’ - one of 30 papers selected from 1,200 NIME papers to be included in the book ‘A NIME Reader: Fifteen Years of New Interfaces for Musical Expression, published by Springer and edited by Alexander Refsum Jensenius and Michael J. Lyons
Charakterisierung der Aktivierung des antiapoptoischen Phosphatidylinositol-3'-Kinase-abhängigen Signalwegs durch den neuroprotektiven Faktor Glial cell line derived neurothrophic factor (GDNF)
No full textAuthor Correction: A shared neural basis underlying psychiatric comorbidity
No full textCorrection to: Nature Medicine. Published online 24 April 2023. In the version of this article initially published, the STRATIFY data also included cohort data from the ESTRA consortium, though this was not acknowledged in the author list and the section in Methods on the Stratify dataset. The Methods are now updated, and the author list is amended to combine the STRATIFY and ESTRA consortium names and to include the following authors: Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Hervé Lemaître, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris and Sylvane Desrivières. The STRATIFY and ESTRA consortia are now combined to list Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Gareth J. Barker, Arun L. W. Bokde, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris, Henrik Walter, Robert Whelan, Sylvane Desrivières and Gunter Schumann as members, and the IMAGEN consortium is updated to also include Sylvane Desrivières. Affiliations, author contributions and acknowledgements have been updated to reflect the new authorship, and all changes have been made in the HTML and PDF versions of the article
Charakterisierung der Aktivierung des antiapoptoischen Phosphatidylinositol-3'-Kinase-abhängigen Signalwegs durch den neuroprotektiven Faktor Glial cell line derived neurothrophic factor (GDNF)
No full textThe role of nicotinic acetylcholine receptor alpha 7 in intensive care unit acquired weakness (ICUAW) in an experimental rat model
No full textIm Rattenmodell wurde überprüft, ob durch extraartikuläres Pinning induzierte Immobilisation bzw. durch intravenöse Applikation von Corynebacterium parvum ausgelöste Infektion zu einer verstärkten Expression postsynaptischer nikotinischer Acetylcholinrezeptoren alpha7 führen. Zudem wurde untersucht, ob eine Therapie mittels GTS-21 die Zunahme der Rezeptorexpression abschwächt. Während alleinige Immobilisation die Rezeptorexpression nicht signifikant erhöhte, war sie infolge von Infektion um das 11-fache erhöht. Therapie reduzierte die Rezeptorexpression signifikant.This study examines in an experimental rat model whether immobilization due to extraarticular pinning and infection due to intravenous injection of Corynebacterium parvum may cause an upregulation of postsynaptic nicotinic acetylcholine receptors alpha7. In addition, it was hypothesized that treatment with GTS-21 can attenuate the elevation of receptor expression. Whereas immobilization alone had no significant effect, receptor expression was increased 11-fold by infection. Therapy resulted in a significantly reduced receptor expression
Gene expression profiling of liver metastases and tumour invasion in pancreatic cancer using an orthotopic SCID mouse model
No full textThe prognosis of pancreatic adenocarcinoma is affected by early metastases and local tumour invasion beyond surgical margins. Gene expression profiling in pancreatic cancer tissue is complicated due to the high amount of RNAses being present in human tissue and that of suitable models. In order to demonstrate early metastases, the models should take into account the anatomical environment of the tumour. Using the orthotopic transplantation of pancreatic tumour cells in SCID (severe combined immunodeficiency) mice, these interactions are taken into consideration. In order to identify genes associated with local tumour invasion and metastases in ductal pancreatic cancer, we investigated a human pancreatic tumour cell line derived from an orthopic pancreatic tumour model in SCID mice. Differential gene expression was performed on the basis of microarray technique. The human MiaPaca-2 cell line was implanted orthotopically in SCID mice. Transcriptional profiling was performed on fresh frozen tissue derived from the primary tumour, the tumour invasion front and the liver metastases. Differentially expressed genes were identified using statistical analyses, and were validated with external databases and with immunohistochemistry. A total of 1066 of 14 500 genes were significantly differentially expressed. Comparing the primary tumour with the tumour invasion front, there were 614 statistically significant up-and 348 downregulated genes. Twenty-five statistically significant up- and 181 downregulated genes were identified comparing the liver metastases with the primary tumour. Eight genes (PAI-1, BNIP31, VEGF, NSE, RGS4, HSP27, GADD45A, PTPN14) were chosen and validated in a semi-quantitative immunohistochemical analysis, which revealed a positive correlation to the array data. Overrepresentation analyses revealed a total of 66 significantly regulated pathways associated with cell proliferation, cell stress, cell communication metabolic and cytokine function. In conclusion, model marker genes for local invasion and liver metastases can be identified using transcriptional profiling in the SCID mouse. Overrepresentation analysis secures a good and fast overview about the significantly regulated genes and can assign genes to certain pathways. These marker genes can be related to the apoptotic cascade, angiogenesis and cell interaction
List of standards and ontologies in mouse image data sets
No full textThe WP6 use case addresses interoperability of large-scale image data sets, which is required for reusing and analysing data sets generated by different sources.
The following aspects of image data sets significantly influence their interoperability:
File formats
Accessibility of the data
Image annotation
Image datasets within the mouse scientist community consist mainly of proprietary raw image formats provided by the proprietary software running the slide scanning machines. This high diversity contributes to the low interoperability of the data coming from different sources. Especially the international mouse phenotyping consortium (IMPC) provides harmonisation approaches regarding the data sources and file formats. Here, the most commonly used file formats are ndpi-files as raw format which can be converted into jpg or tiff files. These image will be made visible within a public accessible database in an annotated form.
Finally, consistent annotation of mouse tissue image data sets is required for their interoperability. Although some ontologies for mouse anatomy and mouse pathology are available, none of them covers comprehensively the histological or the cytological phenotype. Therefore, image data sets are normally annotated using free text or a diverse set of ontologies. To bridge the gap between existing ontologies, WP6 partners are currently developing the cellular microscopy phenotype ontology (CMPO).The report is deliverable 6.2 of BioMedBridges and is related to deliverables 6.1 (cellular image data) and 6.3 (human image data
Author Correction: A shared neural basis underlying psychiatric comorbidity
No full textCorrection to: Nature Medicine https://doi.org/10.1038/s41591-023-02317-4. Published online 24 April 2023. In the version of this article initially published, the STRATIFY data also included cohort data from the ESTRA consortium, though this was not acknowledged in the author list and the section in Methods on the Stratify dataset. The Methods are now updated, and the author list is amended to combine the STRATIFY and ESTRA consortium names and to include the following authors: Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Hervé Lemaître, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris and Sylvane Desrivières. The STRATIFY and ESTRA consortia are now combined to list Marina Bobou, M. John Broulidakis, Betteke Maria van Noort, Zuo Zhang, Lauren Robinson, Nilakshi Vaidya, Jeanne Winterer, Yuning Zhang, Sinead King, Gareth J. Barker, Arun L. W. Bokde, Hervé Lemaître, Frauke Nees, Dimitri Papadopoulos Orfanos, Ulrike Schmidt, Julia Sinclair, Argyris Stringaris, Henrik Walter, Robert Whelan, Sylvane Desrivières and Gunter Schumann as members, and the IMAGEN consortium is updated to also include Sylvane Desrivières. Affiliations, author contributions and acknowledgements have been updated to reflect the new authorship, and all changes have been made in the HTML and PDF versions of the article.</p
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