المؤلفون: Hollestein, J.M.V., Poelmans, G.J.V., Forde, J.N., Beckmann, C.F., Ecker, C., Mann, C., Buitelaar, J.K., Naaijen, J.

المصدر: Translational Psychiatry, 13, 1

مصطلحات موضوعية: All institutes and research themes of the Radboud University Medical Center, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 290131.pdf (Publisher’s version ) (Open Access)

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/290131/290131.pdfTest; https://repository.ubn.ru.nl/handle/2066/290131Test

الإتاحة: https://doi.org/10.1038/s41398-023-02317-5Test
https://repository.ubn.ru.nl//bitstream/handle/2066/290131/290131.pdfTest
https://repository.ubn.ru.nl/handle/2066/290131Test

المؤلفون: Kluivers, K.B., Lince, S.L., Ruiz Zapata, A.M., Post, W.M., Cartwright, R., Kerkhof, M.H, Widomska, J.M., Witte, Ward De, Pecanka, J., Kiemeney, L.A.L.M., Vermeulen, H.H., Goeman, J.J., Allen-Brady, K., Oosterwijk, E., Poelmans, G.J.V.

المصدر: International Journal of Molecular Sciences, 24, 7

مصطلحات موضوعية: All institutes and research themes of the Radboud University Medical Center, Radboudumc 10: Reconstructive and regenerative medicine Gynaecology, Radboudumc 15: Urological cancers Health Evidence, Radboudumc 15: Urological cancers Human Genetics, Radboudumc 15: Urological cancers Primary and Community Care, Radboudumc 15: Urological cancers Urology, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 291876.pdf (Publisher’s version ) (Open Access) ; Pelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform an exome chip study in 526 women with POP and 960 control women to identify single nucleotide variants (SNVs) associated with the disease. We then integrated the functional interactions between the POP candidate proteins derived from the exome chip study and other POP candidate molecules into a molecular landscape. We found significant associations between POP and SNVs in 54 genes. The proteins encoded by 26 of these genes fit into the molecular landscape, together with 43 other POP candidate molecules. The POP landscape is located in and around epithelial cells and fibroblasts of the urogenital tract and harbors four interacting biological processes-epithelial-mesenchymal transition, immune response, modulation of the extracellular matrix, and fibroblast function-that are regulated by sex hormones and TGFB1. Our findings were corroborated by enrichment analyses of differential gene expression data from an independent POP cohort. Lastly, based on the landscape and using vaginal fibroblasts from women with POP, we predicted and showed that metformin alters gene expression in these fibroblasts in a beneficial direction. In conclusion, our integrated molecular landscape of POP provides insights into the biological processes underlying the disease and clues towards novel treatments.

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/291876/291876.pdfTest; https://repository.ubn.ru.nl/handle/2066/291876Test

الإتاحة: https://doi.org/10.3390/ijms24076087Test
https://repository.ubn.ru.nl//bitstream/handle/2066/291876/291876.pdfTest
https://repository.ubn.ru.nl/handle/2066/291876Test

المؤلفون: Post, W.M., Widomska, J.M., Oosterwijk, E., Witte, W. de, Coenen, M.J.H., Janssen, D.A.W., Martens, F.M.J., Cartwright, R., Minassian, V., Penney, K., Thomas, L., Skogholt, A., Stafne, S., Hveem, K., Kluivers, K.B., Poelmans, G.J.V.

المصدر: Ju Open Plus, 1, 4

مصطلحات موضوعية: Radboudumc 10: Reconstructive and regenerative medicine Gynaecology, Radboudumc 10: Reconstructive and regenerative medicine Urology, Radboudumc 15: Urological cancers Urology, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 301331.pdf (Publisher’s version ) (Open Access)

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/301331/301331.pdfTest; https://repository.ubn.ru.nl/handle/2066/301331Test

الإتاحة: https://doi.org/10.1097/JU9.0000000000000019Test
https://repository.ubn.ru.nl//bitstream/handle/2066/301331/301331.pdfTest
https://repository.ubn.ru.nl/handle/2066/301331Test

المؤلفون: Li, S., Poelmans, G.J.V., Boekel, R.L.M. van, Coenen, M.J.H.

المصدر: Pharmacogenomics Journal, 23, 6, pp. 161-168

مصطلحات موضوعية: All institutes and research themes of the Radboud University Medical Center, Radboudumc 18: Healthcare improvement science Anesthesiology, Radboudumc 5: Inflammatory diseases Human Genetics, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 300024.pdf (Publisher’s version ) (Closed access) ; The pharmacological management of musculoskeletal pain starts with NSAIDs, followed by weak or strong opioids until the pain is under control. However, the treatment outcome is usually unsatisfying due to inter-individual differences. To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P = 3.88 × 10(-8)). Suggestive significant (P < 1 × 10(-6)) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development. Pathway and network analyses identified immunity-related processes and a (putative) central role of EGFR. However, this study should be viewed as a first step to elucidate the genetic background of musculoskeletal pain treatment. ; 01 november 2023

العلاقة: https://repository.ubn.ru.nl/handle/2066/300024Test

الإتاحة: https://doi.org/10.1038/s41397-023-00314-xTest
https://repository.ubn.ru.nl/handle/2066/300024Test

المؤلفون: Straathof, M., Blezer, E.L.A., Smeele, C.E., Heijningen, C. van, Toorn, A. van der, Buitelaar, J.K., Glennon, J.C., Naaijen, J., Akkermans, S.E.A., Mennes, M.J.J., Zwiers, M.P., Ilbegi, S., Hennissen, L., Vondervoort, I.I.G.M. van de, Kapusta, K.A., Bielczyk, N.Z., Amiri, H., Havenith, M.N., Franke, B., Poelmans, G.J.V., Bralten, J.B., Heskes, T., Sokolova, E.S., Groot, P., Otte, W.M., Dijkhuizen, R.M.

المساهمون: Radiology and nuclear medicine, Adult Psychiatry

المصدر: TACTICS Consortium 2022, ' Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior ', Psychopharmacology, vol. 239, no. 8, pp. 2457-2470 . https://doi.org/10.1007/s00213-022-06139-zTest
Psychopharmacology, 239, 2457-2470
PSYCHOPHARMACOLOGY
Psychopharmacology, 239(8), 2457-2470. Springer Verlag
Psychopharmacology, 239, 8, pp. 2457-2470

مصطلحات موضوعية: Neuroinformatics, Pharmacology, AUTISM SPECTRUM, DISORDER, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Diffusion magnetic resonance imaging, Data Science, Functional magnetic resonance imaging, Frontostriatal circuitry, DOPAMINE-GLUTAMATE INTERACTIONS, ROBUST, 220 Statistical Imaging Neuroscience, imaging, NMDA antagonist, 150 000 MR Techniques in Brain Function, MECHANISMS, ACTIVATION, Compulsive behavior, DOUBLE-BLIND, NMDA, 130 000 Cognitive Neurology & Memory, Medicine and Health Sciences, REGISTRATION, OPTIMIZATION, Functional magnetic resonance

الوصف: Rationale Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment. Objective Our goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior and frontostriatal network structure and function in an adolescent rat model of compulsivity. Methods Juvenile Sprague–Dawley rats received repeated quinpirole, resulting in compulsive checking behavior (n = 32; compulsive) or saline injections (n = 32; control). Eight compulsive and control rats received chronic memantine treatment, and eight compulsive and control rats received saline treatment for seven consecutive days between the 10th and 12th quinpirole/saline injection. Compulsive checking behavior was assessed, and structural and functional brain connectivity was measured with diffusion MRI and resting-state fMRI before and after treatment. The other rats received an acute single memantine (compulsive: n = 12; control: n = 12) or saline injection (compulsive: n = 4; control: n = 4) during pharmacological MRI after the 12th quinpirole/saline injection. An additional group of rats received a single memantine injection after a single quinpirole injection (n = 8). Results Memantine treatment did not affect compulsive checking nor frontostriatal structural and functional connectivity in the quinpirole-induced adolescent rat model. While memantine activated the frontal cortex in control rats, no significant activation responses were measured after single or repeated quinpirole injections. Conclusions The lack of a memantine treatment effect in quinpirole-induced compulsive adolescent rats may be partly explained by the interaction between glutamatergic and dopaminergic receptors in the brain, which can be evaluated with functional MRI.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::090e1349563e03f387c6cc9476f59b89Test
https://research.vumc.nl/en/publications/7d730c36-f39b-46e3-9b2d-d05af31997f7Test

المؤلفون: Linden, R.J. van der, Gerritsen, J.S., Liao, M., Widomska, J.M., Pearse, R.V., 2nd, White, F.M., Franke, B., Young-Pearse, T., Poelmans, G.J.V.

المصدر: Progress in Neurobiology, 217

مصطلحات موضوعية: Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 281798.pdf (Publisher’s version ) (Open Access) ; The RNA binding protein ELAVL4/HuD regulates the translation and splicing of multiple Alzheimer's disease (AD) candidate genes. We generated ELAVL4 knockout (KO) human induced pluripotent stem cell-derived neurons to study the effect that ELAVL4 has on AD-related cellular phenotypes. ELAVL4 KO significantly increased the levels of specific APP isoforms and intracellular phosphorylated tau, molecular changes that are related to the pathological hallmarks of AD. Overexpression of ELAVL4 in wild-type neurons and rescue experiments in ELAVL4 KO cells showed opposite effects and also led to a reduction of the extracellular amyloid-beta (Aβ)42/40 ratio. All these observations were made in familial AD (fAD) and fAD-corrected neurons. To gain insight into the molecular cascades involved in neuronal ELAVL4 signaling, we conducted pathway and upstream regulator analyses of transcriptomic and proteomic data from the generated neurons. These analyses revealed that ELAVL4 affects multiple biological pathways linked to AD, including those involved in synaptic function, as well as gene expression downstream of APP and tau signaling. The analyses also suggest that ELAVL4 expression is regulated by insulin receptor-FOXO1 signaling in neurons. Taken together, ELAVL4 expression ameliorates AD-related molecular changes in neurons and affects multiple synaptic pathways, making it a promising target for novel drug development.

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/281798/281798.pdfTest; https://repository.ubn.ru.nl/handle/2066/281798Test

الإتاحة: https://doi.org/10.1016/j.pneurobio.2022.102316Test
https://repository.ubn.ru.nl//bitstream/handle/2066/281798/281798.pdfTest
https://repository.ubn.ru.nl/handle/2066/281798Test

المؤلفون: Fanelli, G., Franke, B., Witte, Ward De, Hyun Ruisch, I., Haavik, Jan, Gils, Veerle van, Buitelaar, J.K., Roth Mota, N., Poelmans, G.J.V., Bralten, J.B.

المصدر: Translational Psychiatry, 12, 1

مصطلحات موضوعية: All institutes and research themes of the Radboud University Medical Center, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 247738.pdf (Publisher’s version ) (Open Access)

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/247738/247738.pdfTest; https://repository.ubn.ru.nl/handle/2066/247738Test

الإتاحة: https://doi.org/10.1038/s41398-022-01817-0Test
https://repository.ubn.ru.nl//bitstream/handle/2066/247738/247738.pdfTest
https://repository.ubn.ru.nl/handle/2066/247738Test

المؤلفون: Horjus, Julia, Mourik-Banda, Tineke van, Heerings, M.A.P., Hakobjan, M.H., Witte, Ward De, Heersema, Dorothea J., Franke, B., Visser, L.J., Poelmans, G.J.V.

المصدر: International Journal of Molecular Sciences, 23, 19

مصطلحات موضوعية: All institutes and research themes of the Radboud University Medical Center, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 283845.pdf (Publisher’s version ) (Open Access)

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/283845/283845.pdfTest; https://repository.ubn.ru.nl/handle/2066/283845Test

الإتاحة: https://doi.org/10.3390/ijms231911461Test
https://repository.ubn.ru.nl//bitstream/handle/2066/283845/283845.pdfTest
https://repository.ubn.ru.nl/handle/2066/283845Test

المؤلفون: Wimberley, Theresa, Horsdal, Henriette T., Brikell, Isabell, Laursen, Thomas M., Astrup, Aske, Fanelli, G., Bralten, J.B., Poelmans, G.J.V., Franke, B., Dalsgaard, Soren

المصدر: BMC Psychiatry, 22, 1

مصطلحات موضوعية: All institutes and research themes of the Radboud University Medical Center, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 253636.pdf (Publisher’s version ) (Open Access)

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/253636/253636.pdfTest; https://repository.ubn.ru.nl/handle/2066/253636Test

الإتاحة: https://doi.org/10.1186/s12888-022-04163-zTest
https://repository.ubn.ru.nl//bitstream/handle/2066/253636/253636.pdfTest
https://repository.ubn.ru.nl/handle/2066/253636Test

المؤلفون: Post, W.M., Widomska, J.M., Grens, H., Coenen, M.J.H., Martens, F.M.J., Janssen, D.A.W., Hout, J. in 't, Poelmans, G.J.V., Oosterwijk, E., Kluivers, K.B.

المصدر: International Journal of Molecular Sciences, 23, 6

مصطلحات موضوعية: Radboudumc 10: Reconstructive and regenerative medicine RIHS: Radboud Institute for Health Sciences, Radboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life Sciences, Radboudumc 15: Urological cancers RIMLS: Radboud Institute for Molecular Life Sciences, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, Radboudumc 18: Healthcare improvement science RIHS: Radboud Institute for Health Sciences, Radboudumc 5: Inflammatory diseases RIHS: Radboud Institute for Health Sciences, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience

الوصف: Contains fulltext : 248286.pdf (Publisher’s version ) (Open Access) ; Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

العلاقة: https://repository.ubn.ru.nl//bitstream/handle/2066/248286/248286.pdfTest; https://repository.ubn.ru.nl/handle/2066/248286Test

الإتاحة: https://doi.org/10.3390/ijms23063401Test
https://repository.ubn.ru.nl//bitstream/handle/2066/248286/248286.pdfTest
https://repository.ubn.ru.nl/handle/2066/248286Test