A5073666354- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- Nerve injury and regeneration
- 3D Printing in Biomedical Research
- Epigenetics and DNA Methylation
- Nuclear Receptors and Signaling
- Photoreceptor and optogenetics research
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Polymer Surface Interaction Studies
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Neural dynamics and brain function
- RNA Interference and Gene Delivery
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Alzheimer's disease research and treatments
- Histone Deacetylase Inhibitors Research
- Plant-derived Lignans Synthesis and Bioactivity
- Calcium signaling and nucleotide metabolism
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2013-2024
Polish Academy of Sciences
2009-2024
University of Warsaw
2024
University of Cincinnati Medical Center
2017
Most mitochondrial proteins originate from the cytosol and require transport into organelle. Such precursor must be unfolded to pass through translocation channels in membranes. Misfolding of transported can result their arrest failure. Arrested block further import, disturbing functions cellular proteostasis. Cellular responses failure have been defined yeast. We developed cell line-based translocase clogging model discover molecular mechanisms that resolve failed import events humans. The...
Studies in cultured cells have demonstrated the existence of higher-order epigenetic mechanisms, determining relationship between expression gene and its position within cell nucleus. It is unknown, whether such mechanisms operate postmitotic, highly differentiated types, as neurons vivo. Accordingly, we examined intranuclear positions Bdnf Trkb genes, encoding major neurotrophin receptor respectively, change a result neuronal activity, what functional consequences movements may have. In rat...
Abstract The human genome is extensively folded into 3-dimensional organization. However, the detailed 3D chromatin folding structures have not been fully visualized due to lack of robust and ultra-resolution imaging capability. Here, we report development an electron microscopy method that combines serial block-face scanning with in situ hybridization (3D-EMISH) visualize at targeted genomic regions (5 × 5 30 nm xyz dimensions) superior current super-resolution by fluorescence light...
Abstract The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins forebrain excitatory mice resulted a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction reduced electrical activity. At molecular level, observed downregulation neuronal genes, as well...
Abstract Besides cell death, autophagy and senescence are the main outcomes of anticancer treatment. We demonstrate that tacrine-melatonin heterodimer C10, a potent anti-Alzheimer’s disease drug, has an antiproliferative effect on MCF-7 breast cancer cells. The response to 24 h-treatment with C10 was enhancement accompanied by inhibition mTOR AKT pathways. Significantly increased markers, such as LC3B- ATG16L-positive vesicles, confirmed induction C10. However, analysis autophagic flux using...
Copper-induced structural rearrangements of Abeta40 structure and its redox properties are described in this study. Electrochemical fluorescent methods used to characterise the behaviour Abeta-Cu species. The data suggest that time-dependent folding species may cause changes potentials.Extracellular deposits beta-amyloid (Abeta) into senile plaques major features observed brains Alzheimer's disease (AD) patients. A high concentration copper has been associated with insoluble amyloid plaques....
Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome response to external stimuli. We show that stimulation of causes condensation large domains. This phenomenon can observed vitro cultured rat hippocampal as well vivo the amygdala neurons. Activity-induced an active, rapid, energy-dependent, reversible process. It involves calcium-dependent pathways but independent active...
Epilepsy is one of the most common chronic neurological disorders, affecting around 50 million people worldwide, but its underlying cellular and molecular events are not fully understood. The Golgi a highly dynamic organelle can be fragmented into ministacks under both physiological pathological conditions. This phenomenon has also been observed in several neurodegenerative disorders; however, structure apparatus (GA) human patients suffering from epilepsy described so far. aim this study...
Podophyllotoxin (PPT) is an active pharmaceutical ingredient (API) with established antitumor potential. However, due to its systemic toxicity, use restricted topical treatment of anogenital warts. Less toxic PPT derivatives (e.g., etoposide and teniposide) are used intravenously as anticancer agents. has been exploited a scaffold new potential therapeutic agents; however, fewer studies have conducted on the parent molecule than derivatives. We undertaken study ultrastructural changes...
Due to the limited number of organ donors, 3D printing organs is a promising technique. Tissue engineering increasingly using xenogeneic material for this purpose. This study was aimed at assessing safety decellularized porcine pancreas, together with analysis risk an undesirable immune response. We tested eight variants decellularization process. determined following impacts: rinsing agents (PBS/NH3·H2O), temperature conditions (4 °C/24 °C), and grinding method native (ground/cut). To...
Abnormalities that characterize the pathophysiology of type 2 diabetes (T2D) include deficiencies β-cells and expansion α-cells in pancreatic islets, manifested by lower insulin release glucagon oversecretion. The molecular mechanisms determine intra-islet interactions between α- are still not fully understood. present study showed stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), an enzyme is implicated fatty acid metabolism, serves as a checkpoint control endocrine cell equilibrium islets....
Podophyllotoxin (PPT) is an antimitotic drug used topically in the treatment of anogenital warts. Due to its toxicity it cannot be administered systemically as anticancer agent. However, modified PPT derivatives such etoposide and teniposide are clinically systemic agents. Thus, we invented novel derivative KL3 that was synthesized by photocyclization. Earlier have shown has effect various cell lines. Here compared vs on non-cancerous normal human keratinocytes (HaCaT) peripheral blood...
Abstract The effect of polystyrene surface polarity on the conformation adsorbed fibronectin (FN) has been studied with atomic force microscopy. We demonstrated that bare sulfonated and nonsulfonated surfaces featured similar topographies. After FN adsorption, direct comparison both types substrata revealed drastically different topographies, roughness values, also cell‐adhesive properties. This was interpreted in terms conformational changes induced by polarity. At high‐solute...
Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative that displays great genetic heterogeneity. The genes and mutations underlie this heterogeneity have been extensively characterized by molecular genetics. However, the pathogenesis of vast majority CMT subtypes remains terra incognita. Any attempts to perform experimental therapy for are limited lack understanding at level. In study, we aim identify pathways disturbed in gene encoding GDAP1 using both yeast human cell, based...
The Brain-Derived Neurotrophic Factor is one of the most important trophic proteins in brain. role this growth factor neuronal plasticity, health and disease, has been extensively studied. However, mechanisms epigenetic regulation Bdnf gene expression epilepsy are still elusive. In our previous work, using a rat model activation upon kainate-induced seizures, we observed repositioning alleles from nuclear periphery towards center. This change intranuclear position was associated with...
The detailed architectural examination of the neuronal nuclei in any brain region, using confocal microscopy, requires quantification fluorescent signals three-dimensional stacks images. An essential prerequisite to is segmentation which are typically tightly packed tissue, extreme being hippocampal dentate gyrus (DG), frequently appear overlap due limitations microscope resolution. Segmentation DG a challenging task presence significant amount image artifacts and densely nuclei....
Abstract Nuclear speckles, also known as interchromatin granule clusters (IGCs), are subnuclear domains highly enriched in proteins involved transcription and mRNA metabolism and, until recently, have been regarded primarily their storage modification hubs. However, several recent studies on non-neuronal cell types indicate that nuclear speckles may directly contribute to gene expression some of the active genes shown associate with these structures. Neuronal activity is one key...
After spinal cord transection (SCT) the interaction between motoneurons (MNs) and muscle is impaired, due to reorganization of network after a loss supraspinal inputs. Rats subjected SCT, treated with intraspinal injection AAV-BDNF (brain-derived neurotrophic factor) construct, partially regained ability walk. The central effects this treatment have been identified, but its impact at neuromuscular junction (NMJ) has not characterized. Here, we compared NMJ pre- postsynaptic machinery in...
Metal-based agents in cancer therapy, like cisplatin and its derivates, have established clinical applications but also can induce serious side effects. Thus, metallotherapeutic alternatives for platinum derivatives are developed intensively studied. Platinum is replaced by several transition metals including gold. Especially gold (III) complexes the same square-planar structure isoelectric with (II). Hence, they as potential anti-cancer drugs. our group projected a of novel cyanide-based...