Marjolein Bosma

Comprehensive genotypic, phenotypic, and biochemical characterization of GOT2 deficiency: A progressive neurodevelopmental disorder with epilepsy and abnormal movements

Hannah M German, Maha Saad Zaki, Muhammad Asad Usmani, Irem Karagoz et autres

PURPOSE: Glutamic-oxaloacetic transaminase (GOT), also known as aspartate aminotransferase, catalyzes the reversible transamination of oxaloacetate and glutamate to aspartate and α-ketoglutarate. Two isoforms, cytosolic (GOT1) and mitochondrial (GOT2), are integral to the malate-aspartate shuttle, a key regulator of intracellular redox homeostasis. Recently, …

nl, Égypte, us, pk, gb, jo, ir, tr (code pays fourni par la source)

Fecal gut microbiota and amino acids as noninvasive diagnostic biomarkers of Pediatric inflammatory bowel disease

Eva Vermeer, Jasmijn Z. Jagt, Eline M. Lap, Eduard A. Struys et autres

Background and Aims Fecal calprotectin (FCP) has limited specificity as diagnostic biomarker of pediatric inflammatory bowel disease (IBD), leading to unnecessary invasive endoscopies. This study aimed to develop and validate a fecal microbiota and amino acid (AA)-based diagnostic model.Methods Fecal samples from …

nl, gb (code pays fourni par la source)

S-adenosylmethionine addiction confers sensitivity to methionine restriction in KMT2A-rearranged acute lymphoblastic leukemia

Trisha M. Tee, Titine J.J. Ruiter, Shuiyan Wu, Weiya Zhang et autres

Current intensive chemotherapy regimens have improved overall survival in pediatric acute lymphoblastic leukemia (ALL) but fail to cure some high-risk patient subgroups. We observed that lysine methyltransferase 2A-rearranged (KMT2A-r) leukemia, an aggressive subset with a dismal prognosis, is particularly vulnerable to perturbations …

nl, cn (code pays fourni par la source)

Broad Vitamin B6-Related Metabolic Disturbances in a Zebrafish Model of Hypophosphatasia (TNSALP-Deficiency)

Jolita Čiapaitė, Monique Albersen, Sanne M. C. Savelberg, Marjolein Bosma et autres

Hypophosphatasia (HPP) is a rare inborn error of metabolism caused by pathogenic variants in ALPL, coding for tissue non-specific alkaline phosphatase. HPP patients suffer from impaired bone mineralization, and in severe cases from vitamin B6-responsive seizures. To study HPP, we generated alpl-/- …

nl (code pays fourni par la source)

Broad Vitamin B6-Related Metabolic Disturbances in a Zebrafish Model of Hypophosphatasia (Alpl-Deficiency)

Jolita Čiapaitė, Monique Albersen, Sanne M. C. Savelberg, Marjolein Bosma et autres

Hypophosphatasia (HPP) is a rare inborn error of metabolism caused by pathogenic var-iants in ALPL, coding for tissue non-specific alkaline phosphatase. HPP patients suffer from impaired bone mineralization and in severe cases from vitamin B6-responsive sei-zures. To study HPP we generated alpl-/- …

mTORC1 restricts TFE3 activity by auto-regulating its presence on lysosomes

Susan Zwakenberg, Denise Westland, Robert M. van Es, Holger Rehmann et autres

To stimulate cell growth, the protein kinase complex mTORC1 requires intracellular amino acids for activation. Amino-acid sufficiency is relayed to mTORC1 by Rag GTPases on lysosomes, where growth factor signaling enhances mTORC1 activity via the GTPase Rheb. In the absence of amino …

nl, de (code pays fourni par la source)

The malate-aspartate shuttle is important for de novo serine biosynthesis

Melissa H. Broeks, Nils W. F. Meijer, Denise Westland, Marjolein Bosma et autres

The malate-aspartate shuttle (MAS) is a redox shuttle that transports reducing equivalents across the inner mitochondrial membrane while recycling cytosolic NADH to NAD + . We genetically disrupted each MAS component to generate a panel of MAS-deficient HEK293 cell lines in which …

nl (code pays fourni par la source)

Maintenance of cellular vitamin B6 levels and mitochondrial oxidative function depend on pyridoxal 5′-phosphate homeostasis protein

Jolita Čiapaitė, Carlo W.T. van Roermund, Marjolein Bosma, Johan Gerrits et autres

Recently, biallelic variants in PLPBP coding for pyridoxal 5'-phosphate homeostasis protein (PLPHP) were identified as a novel cause of early-onset vitamin B 6 -dependent epilepsy. The molecular function and precise role of PLPHP in vitamin B 6 metabolism are not well understood. …

nl, us, ca (code pays fourni par la source)

Correction to: Pyridox (am) ine 5'-phosphate oxidase deficiency induces seizures in Drosophila melanogaster

Wanhao Chi, Atulya Iyengar, Monique Albersen, Marjolein Bosma et autres

In the originally published version of this manuscript, there was an error in Figure 3A with the arrows mismatching with the enzymes. This has been corrected.

us, nl (code pays fourni par la source)

A novel mouse model for pyridoxine-dependent epilepsy due to antiquitin deficiency

Hilal H. Al-Shekaili, Terri L. Petkau, Izabella Agostinho Pena, Tess C. Lengyell et autres

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease caused by mutations in the ALDH7A1 gene leading to blockade of the lysine catabolism pathway. PDE is characterized by recurrent seizures that are resistant to conventional anticonvulsant treatment but are well-controlled by pyridoxine …

ca, us, nl (code pays fourni par la source)

NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet Syndrome

Wout J. Weuring, Sakshi Singh, Linda Volkers, Martin B. Rook et autres

Dravet syndrome is caused by dominant loss-of-function mutations in SCN1A which cause reduced activity of Nav1.1 leading to lack of neuronal inhibition. On the other hand, gain-of-function mutations in SCN8A can lead to a severe epileptic encephalopathy subtype by over activating NaV1.6 …

nl, au, it (code pays fourni par la source)

Pyridox(am)ine 5′-phosphate oxidase (PNPO) deficiency in zebrafish results in fatal seizures and metabolic aberrations

Jolita Čiapaitė, Monique Albersen, Sanne M. C. Savelberg, Marjolein Bosma et autres

Pyridox(am)ine 5′-phosphate oxidase (PNPO) catalyzes oxidation of pyridoxine 5′-phosphate (PNP) and pyridoxamine 5′-phosphate (PMP) to pyridoxal 5′-phosphate (PLP), the active form of vitamin B6. PNPO deficiency results in neonatal/infantile seizures and neurodevelopmental delay. To gain insight into this disorder we generated Pnpo …

nl (code pays fourni par la source)