Aat A. Mulder

USH2A High-Capacity Adenoviral Vector Restores usherin, whirlin, and ADGRV1 in Photoreceptor Cells of Retinal Organoids

Rossella Valenzano, Xuefei Lu, Aat A. Mulder, Elon H.C. van Dijk et autres

Development of gene therapies for USH2A -associated diseases has been limited by the large size of the USH2A coding sequence, which exceeds the packaging capacity of adeno-associated viral vectors. Here, we evaluated high-capacity adenoviral vectors (HC-AdVs) as vehicles for a mutation-independent USH2A …

nl (code pays fourni par la source)

Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids

Rossella Valenzano, Andrew McDonald, Carmen Gallego, Charlotte A. Andriessen et autres

BACKGROUND: Loss-of-function mutations in the ABCA4 gene cause Stargardt disease (STGD1), the most common inherited macular dystrophy leading to progressive central vision loss. METHODS: Here, we generated human induced pluripotent stem cell-derived retinal organoids harboring a premature stop codon in exon-24 of …

nl (code pays fourni par la source)

Loss of ABCA4 from photoreceptor discs triggers changes in glial cell homeostasis

Rossella Valenzano, Andrew McDonald, Carmen Gallego, Charlotte A. Andriessen et autres

Abstract Loss-of-function mutations in the ABCA4 gene cause Stargardt disease (STGD1), the most common inherited macular dystrophy leading to progressive central vision loss. Here, we generated hiPSC-derived retinal organoids harboring a premature stop codon in exon-24 of ABCA4 to evaluate the impact …

nl (code pays fourni par la source)

Nonsense Mutation in USH2A Exon-13 Activates the Innate Immune Response in Müller Glial Cells

Rossella Valenzano, Xuefei Lu, Andrew McDonald, Ioannis Moustakas et autres

Pathological USH2A mutations cause Usher syndrome type II, characterized by progressive retinitis pigmentosa and hearing and balance impairment. This study aims to investigate the cellular mechanisms underlying USH2A-related retinal degeneration using human induced pluripotent stem cell (hiPSC)-derived retinal organoids. The introduction of …

nl, us (code pays fourni par la source)

O-GlcNAcylation drives macrophage IL-4 responsiveness and tissue residency through metabolic and cell cycle calibration

Graham A. Heieis, Conor M. Finlay, Thiago A. Patente, Martina Erbì et autres

ABSTRACT The metabolic requirements for macrophage IL-4 polarization remain contentious, while immunometabolic studies of tissue resident macrophages are still sparse. Hexosamine biosynthesis has gained attention regarding its immune regulatory potential via downstream O-GlcNAcylation. Here we identify protein O-GlcNAcylation as a requirement for …

nl, ie, gb (code pays fourni par la source)

Nonsense Mutation in USH2A Exon-13 Activates the Innate Immune Response in Müller Glial Cells

Rossella Valenzano, Xuefei Lu, Andrew McDonald, Ioannis Moustakas et autres

Pathological USH2A mutations cause Usher Syndrome type II, characterized by progres-sive retinitis pigmentosa and hearing and balance impairment. This study aims to inves-tigate the cellular mechanisms underlying USH2A-related retinal degeneration using hu-man induced pluripotent stem cell (hiPSC)-derived retinal organoids. The introduction of …

KLHL24 mutation drives intermediate filament degradation, mitochondrial dysfunction and fibrosis in heart failure patients

Veronika Ramovš, H. Sophia Chen, Rayman T.N. Tjokrodirijo, Peter A. van Veelen et autres

AIMS: A striking aspect of epidermolysis bullosa patients with a mutation in KLHL24 (KLHL24mut) is their life-threatening deterioration of heart function. KLHL24 is a component of the ubiquitin-proteasome system and acts as a substrate-specific adaptor protein for E3 ubiquitin ligase. KLHL24mut is …

nl, dk, cl, de, fr (code pays fourni par la source)

Small Vessel Disease Phenotype Associated With Monoallelic NOTCH3 Loss-of-Function Variants

Josephine S. van Asbeck, Gido Gravesteijn, Minne N. Cerfontaine, Jeroen Vreijling et autres

Monoallelic cysteine-altering NOTCH3 (NOTCH3cys) variants cause the adult-onset small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and biallelic NOTCH3 loss-of-function (NOTCH3lof) variants cause a rare, childhood-onset small vessel disease. Whether monoallelic NOTCH3lof variants also cause a small …

nl, it, gb, us, cy, tw (code pays fourni par la source)

Clinically compliant enrichment of human pluripotent stem cell–derived islets

Bahareh Rajaei, Amadeo Muñoz García, Juri Juksar, Jason B. Doppenberg et autres

Human pluripotent stem cell-derived islet (SC-islet) transplantation is a promising β cell replacement therapy for patients with type 1 diabetes, offering a potential unlimited cell supply. Yet, the heterogeneity of the final cell product containing non-target cell types has relevant implications for …

nl (code pays fourni par la source)

Author response: The ORP9-ORP11 dimer promotes sphingomyelin synthesis

Birol Cabukusta, Shalom Borst Pauwels, Jimmy J.L.L. Akkermans, Niek Blomberg et autres

nl (code pays fourni par la source)

The ORP9-ORP11 dimer promotes sphingomyelin synthesis

Birol Cabukusta, Shalom Borst Pauwels, Jimmy J.L.L. Akkermans, Niek Blomberg et autres

Numerous lipids are heterogeneously distributed among organelles. Most lipid trafficking between organelles is achieved by a group of lipid transfer proteins (LTPs) that carry lipids using their hydrophobic cavities. The human genome encodes many intracellular LTPs responsible for lipid trafficking and the …

nl (code pays fourni par la source)

Author response: The ORP9-ORP11 dimer promotes sphingomyelin synthesis

Birol Cabukusta, Shalom Borst Pauwels, Jimmy J.L.L. Akkermans, Niek Blomberg et autres

Numerous lipids are heterogeneously distributed among organelles. Most lipid trafficking between organelles is achieved by a group of lipid transfer proteins (LTPs) that carry lipids using their hydrophobic cavities. The human genome encodes many intracellular LTPs responsible for lipid trafficking and the …

nl (code pays fourni par la source)