A5068758645- Glioma Diagnosis and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Fatty Acid Research and Health
- Muscle Physiology and Disorders
- Peptidase Inhibition and Analysis
- Cholesterol and Lipid Metabolism
- Protein Structure and Dynamics
- Cancer Cells and Metastasis
- Trace Elements in Health
- Sexual Differentiation and Disorders
- Peroxisome Proliferator-Activated Receptors
- Telomeres, Telomerase, and Senescence
- Free Radicals and Antioxidants
- Developmental Biology and Gene Regulation
- Cognitive Abilities and Testing
- Genomics and Rare Diseases
- Chromatin Remodeling and Cancer
- Heat shock proteins research
- Hereditary Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
University of Belgrade
2000-2024
Deleted Institution
2020
University of Copenhagen
2016
Memorial Sloan Kettering Cancer Center
2009-2015
Cornell University
2010
University of Freiburg
2005-2006
Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail histone H3.3. The role H3.3K27M mutation tumorigenesis is not fully understood. Here, we use human embryonic stem cell system to model this tumor. We show expression synergizes with p53 loss and PDGFRA activation neural progenitor cells derived from cells, resulting neoplastic transformation....
Abstract Glioblastoma multiforme (GBM) is a highly heterogeneous malignant tumor. Recent data suggests the presence of hierarchical organization within GBM cell population that involves cancer cells with stem-like behavior, capable repopulating tumor and contributing to its resistance therapy. Tumor stem are thought reside vascular niche provides structural functional support. However, most studies involve isolated grown under various culture conditions. Here, we use novel three-dimensional...
ATP-dependent oligomeric proteases are major components of cellular protein quality control systems. To investigate the role proteolytic processes in maintenance mitochondrial functions, we analyzed dynamic behavior proteome Saccharomyces cerevisiae by two-dimensional (2D) polyacrylamide gel electrophoresis. By a characterization influence temperature on turnover isolated mitochondria, were able to define four groups proteins showing differential susceptibility proteolysis. The Pim1/LON has...
Abstract The protease Pim1/LON, a member of the AAA+ family homo-oligomeric ATP-dependent proteases, is responsible for degradation soluble proteins in mitochondrial matrix. To establish molecular parameters required specific recognition and proteolysis substrate by Pim1, we analyzed organello imported reporter containing different structural properties. amino acid composition at amino-terminal end had no major effect on reaction. However, with an extension less than 60 acids front stably...
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction a transporting P-type ATPase (ATP7B). Approximately 150 mutations ATP7B have been identified to date. In this paper, we report results molecular characterization and genotype-phenotype analysis, which carried out on 35 patients Yugoslavia affected by WD. Using single-strand conformational polymorphism (SSCP) followed direct sequencing, characterized defect in 80% WD...
The derivation of induced human pluripotent stem cells (hiPS) has generated significant enthusiasm particularly for the prospects cell-based therapy. But there are concerns about suitability iPS in vivo applications due part to introduction potentially oncogenic transcription factors via viral vectors. Recently developed lentiviral vectors allow excision reprogramming and development transgene-free lines. However it is unclear if strategy an impact on differentiation potential behavior hiPS...
Oligodendrocytes are the main myelinating cell of adult CNS and vulnerable to injury in diverse disorders such as spinal cord injury, stroke, trauma, pharmacological radiation toxicity, well neuroinflammation. Human pluripotent stem cells attractive sources oligodendrocyte lineage provide a promising treatment strategy for exogenous myelin repair through transplantation. This unit describes protocol step-wise differentiation forebrain late progenitor (OPCs) from human defined chemical vitro...
Cerebral amyloid angiopathy (CAA) is characterized by β (Aβ) accumulation in the blood vessels and associated with cognitive impairment Alzheimer's disease (AD). The increased of Aβ also present retinal a significant correlation between brain deposition was demonstrated living patients animal AD models. can be result impaired transcytosis and/or dysfunctional ocular glymphatic system during aging. We analyzed changes mRNA protein expression major facilitator superfamily domain-containing...
In patients with Alzheimer’s disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) retinal blood vessels strongly correlates brain deposits cognitive decline. The Aβ may result from impaired transcytosis a dysfunctional ocular glymphatic system AD. High-dose fish oil (FO) supplementation has been shown to significantly change expression major facilitator superfamily domain-containing protein 2a (Mfsd2a), key regulator transcytosis, Aquaporin 4 (Aqp4), an essential...
The recommended fish oil (FO) supplementation doses often yield low omega-3 polyunsaturated fatty acids (PUFAs) tissue bioavailability, and higher (up to 10 g per day) have been increasingly recommended. However, the exact effects of such FO on healthy retina retinal pigmented epithelium (RPE) are unknown. Our study showed that high dose treatment did not imbalance rigorous docosahexaenoic acid (DHA, C22:6n3) homeostasis in RPE three-month-old female B6/SLJ mice. Instead, we found...
Mutations at two fragile sites, FRAXAand FRAXE, loci are caused by an expansion of a CGG/GCC trinucleotide repeat and characterized mental retardation. Here we report molecular screening survey 97 unrelated individuals diagnosed with non-specific retardation (MR), which produced positive test for FRAXAin boys none the FRAXEmutation. In addition, studied allelic frequency distribution FRAXAlocus in this group mentally retarded patients, as well 99 healthy subjects Yugoslav population. The...
Introduction During fetal development, the proper development of neural and visual systems relies on maternal supplementation omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources omega-3, such as fish oil (FO). This has been linked a reduced risk preterm birth, pre-eclampsia, perinatal depression. Recently, higher doses have recommended for pregnant women. Considering that acids, particularly docosahexaenoic acid...
Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for short-term treatment insomnia. Previous publications on zaleplon have not addressed proteins involved in its mechanism action but mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling been shown regulate wakefulness sleep, we examined effects prolonged (0.625 mg/kg 5 days) these systems hippocampus male Wistar rats. Western blot...
A number of human hereditary neuromuscular and neurodegenerative disorders are caused by the expansion trinucleotide repeats within certain genes. The molecular mechanisms that underlie these expansions not yet known. We have analyzed six repeat-containing loci [spinocerebellar ataxias (SCA1, SCA3, SCA8), dentatorubral-pallidoluysian atrophy (DRPLA), Huntington chorea (HD) fragile X syndrome (FRAXA)] in myotonic dystrophy type 1 (DM1) patients (n = 52). As controls, we two groups subjects:...
e22080 Background: Glioblastoma Multiforme (GBM) is highly radioresistant, possibly due to a subpopulation of Brain Tumor “Stem-like‘ Cells (BTSC) capable repopulating the tumor. The Notch signaling pathway essential for maintaining normal neural stem cells. We asked whether inhibition can overcome radioresistance by allowing BTSCs exit their cell state. Methods: To maintain in original niche we used an organotypic culture method (explants). GBM explants are cultured on semiporous membrane...
Radiation therapy (RT) to the brain remains a powerful tool in management of wide range cancers brain, head and neck regions metastases. It is also used prophylaxis treatment regimens for leukemias small cell cancers. There an increasing awareness significant irreversible long-term side effects associated with RT, including cognitive decline impairment motor coordination. Our team others have shown that depletion oligodendrocyte progenitors (OPC) demyelination are major pathological features...
Recent sequencing data demonstrate the presence of novel mutations in H3.3. histone gene variant diffuse intrinsic brainstem gliomas childhood, DIPG. Surgical access to these tumors presents high risks, leading a paucity patient specimens and poor understanding this tumor's biology. We used human embryonic stem cells differentiated into early neural precursors as system model H3.3K27M tumors. vitro vivo neoplastic transformation cells, following expression gene, well combination PDGFRA p53....