| 1. |
- Arthur-Farraj, Peter J., et al.
(author)
-
c-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration
- 2012
-
In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 75:4, s. 633-647
-
Journal article (peer-reviewed)abstract
- The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue.
|
|
| 2. |
|
|
| 3. |
- Corell, Mikael, et al.
(author)
-
GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination
- 2015
-
In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 93:2, s. 285-295
-
Journal article (peer-reviewed)abstract
- The γ-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury.
|
|
| 4. |
- Corell, Mikael, et al.
(author)
-
Spatiotemporal Distribution and Function of N-Cadherin in Postnatal Schwann Cells : A Matter of Adhesion?
- 2010
-
In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 88:11, s. 2338-2349
-
Journal article (peer-reviewed)abstract
- During embryonic development of the peripheral nervous system (PNS), the adhesion molecule neuronal cadherin (N-cadherin) is expressed by Schwann cell precursors and associated with axonal growth cones. N-cadherin expression levels decrease as precursors differentiate into Schwann cells. In this study, we investigated the distribution of N-cadherin in the developing postnatal and adult rat peripheral nervous system. N-cadherin was found primarily in ensheathing glia throughout development, concentrated at neuron glial or glial glial contacts of the sciatic nerve, dorsal root ganglia (DRG), and myenteric plexi. In the sciatic nerve, N-cadherin decreases with age and progress of myelination. In adult animals, N-cadherin was found exclusively in nonmyelinating Schwann cells. The distribution of N-cadherin in developing E17 DRG primary cultures is similar to what was observed in vivo. Functional studies of N-cadherin in these cultures, using the antagonist peptide INPISGQ, show a disruption of the attachment between Schwann cells, but no interference in the initial or long-term contact between Schwann cells and axons. We suggest that N-cadherin acts primarily in the adhesion between glial cells during postnatal development. It may form adherents/junctions between nonmyelinating glia, which contribute to the stable tubular structure encapsulating thin caliber axons and thus stabilize the nerve structure as a whole.
|
|
| 5. |
|
|
| 6. |
- Enoksson, Mattias, et al.
(author)
-
Intraperitoneal influx of neutrophils in response to IL-33 is mast cell-dependent
- 2013
-
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:3, s. 530-536
-
Journal article (peer-reviewed)abstract
- IL-33 is a recently discovered cytokine involved in induction of Th2 responses and functions as an alarmin. Despite numerous recent studies targeting IL-33, its role in vivo is incompletely understood. Here we investigated inflammatory responses to intraperitoneal IL-33 injections in wild-type and mast cell–deficient mice. We found that wild-type mice, but not mast cell–deficient Wsh/Wsh mice, respond to IL-33 treatment with neutrophil infiltration to the peritoneum, whereas other investigated cell types remained unchanged. In Wsh/Wsh mice, the IL-33–induced innate neutrophil response could be rescued by local reconstitution with wild-type but not with T1/ST2−/− mast cells, demonstrating a mast cell–dependent mechanism. Furthermore, we found this mechanism to be partially dependent on mast cell–derived TNF, as we observed reduced neutrophil infiltration in Wsh/Wsh mice reconstituted with TNF−/− bone marrow–derived mast cells compared with those reconstituted with wild-type bone marrow–derived mast cells. In agreement with our in vivo findings, we demonstrate that humanneutrophils migrate toward the supernatant of IL-33–treated human mast cells. Taken together, our findings reveal that IL-33 activates mast cells in vivo to recruit neutrophils, a mechanism dependent on IL-33R expression on peritoneal mast cells. Mast cells activated in vivo by IL-33 probably play an important role in inflammatory reactions.
|
|
| 7. |
- Hanrieder, Jörg, 1980, et al.
(author)
-
MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue.
- 2011
-
In: Analytical and bioanalytical chemistry. - : Springer Science and Business Media LLC. - 1618-2650 .- 1618-2642. ; 401:1, s. 135-47
-
Journal article (peer-reviewed)abstract
- The development of powerful analytical techniques for specific molecular characterization of neural cell types is of central relevance in neuroscience research for elucidating cellular functions in the central nervous system (CNS). This study examines the use of differential protein expression profiling of mammalian neural cells using direct analysis by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). MALDI-MS analysis is rapid, sensitive, robust, and specific for large biomolecules in complex matrices. Here, we describe a newly developed and straightforward methodology for direct characterization of rodent CNS glial cells using MALDI-MS-based intact cell mass spectrometry (ICMS). This molecular phenotyping approach enables monitoring of cell growth stages, (stem) cell differentiation, as well as probing cellular responses towards different stimulations. Glial cells were separated into pure astroglial, microglial, and oligodendroglial cell cultures. The intact cell suspensions were then analyzed directly by MALDI-TOF-MS, resulting in characteristic mass spectra profiles that discriminated glial cell types using principal component analysis. Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination of different cell types with molecular specificity.
|
|
| 8. |
- Karademir, Betul, et al.
(author)
-
Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib
- 2018
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
-
Journal article (peer-reviewed)abstract
- The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications.
|
|
| 9. |
|
|
| 10. |
- Kindlundh-Högberg, Anna M. S., et al.
(author)
-
MDMA (Ecstasy) decreases the number of neurons and stem cells in embryonic cortical cultures
- 2010
-
In: Cellular and molecular neurobiology. - : Springer Science and Business Media LLC. - 0272-4340 .- 1573-6830. ; 30:1, s. 13-21
-
Journal article (peer-reviewed)abstract
- Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 microM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 microM) in NeuN-positive cells. By qPCR, MDMA (200 microM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D(1) receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT(1A) receptor. In conclusion, MDMA caused a marked reduction in stem cells and neurons in embryonic cortical primary cell cultures, which was accompanied by changes in mRNA expression of specific receptors and transporters for glutamatergic and monoaminergic neurotransmitters.
|
|
| 11. |
|
|
| 12. |
- Kundu, Soumi, et al.
(author)
-
Heparanase Promotes Glioma Progression and is Inversely Correlated with Patient Survival.
- 2016
-
In: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 14:12, s. 1243-1253
-
Journal article (peer-reviewed)abstract
- Malignant glioma continues to be fatal, despite improved insight into its underlying molecular mechanisms. The most malignant form, glioblastoma (GBM), is characterized by aberrant activation of receptor tyrosine kinases (RTK) and infiltrative growth. Heparan sulfate proteoglycans (HSPGs), integral components of the extracellular matrix of brain tumors (HPSE), which cleaves HSPGs, for its role in glioma. This hypothesis was evaluated using tissue microarrays, GBM cells derived from patients, murine in vitro and in vivo can regulate activation of many RTK pathways. This prompted us to investigate heparanase models of glioma, and public databases. Down-regulation of HPSE attenuated glioma cell proliferation, while addition of HPSE stimulated growth, and activated ERK and AKT signaling. Using HPSE transgenic and knockout mice it was demonstrated that tumor development in vivo was positively correlated to HPSE levels in the brain. HPSE also modified the tumor microenvironment, influencing reactive astrocytes, microglia/monocytes and tumor angiogenesis. Furthermore, inhibition of HPSE reduces tumor cell numbers, both in vitro and in vivo. HPSE was highly expressed in human glioma and GBM cell lines, compared to normal brain tissue. Indeed, a correlation was observed between high levels of HPSE and shorter survival of patients with high-grade glioma. In conclusion, these data provide proof-of-concept for anti-HPSE treatment of malignant glioma, as well as novel insights for the development of HPSE as a therapeutic target.IMPLICATIONS: This study aims to target both the malignant brain tumor cells per se, and their microenvironment by changing the level of an enzyme, heparanase, that breaks down modified sugar chains on cell surfaces and in the extracellular space.
|
|
| 13. |
|
|
| 14. |
- Pickering, Chris, et al.
(author)
-
A low ethanol dose affects all types of cells in mixed long-term embryonic cultures of the cerebellum
- 2010
-
In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 106:6, s. 472-478
-
Journal article (peer-reviewed)abstract
- The beneficial effect of the '1-drink-a-day' lifestyle is suggested by studies of cardiovascular health, and this recommendation is increasingly followed in many countries. The main objective of this study was to determine whether this pattern of ethanol use would be detrimental to a pregnant woman. We exposed a primary culture of rat cerebellum from embryonic day 17 (corresponding to second trimester in humans) to ethanol at a concentration of 17.6 mM which is roughly equivalent to one glass of wine. Acutely, there was no change in cell viability after 5 or 8 days of exposure relative to control. By 11 days, a reduction in the number of viable cells was observed without an accompanying change in caspase-3 activity (marker of apoptotic cell death), suggesting changes in cell proliferation. As the proportion of nestin-positive cells was higher in the ethanol-treated cultures after 5 days, we hypothesized that an increase in differentiation to neurons would compensate for the ongoing neuronal death. However, there were limits to this compensatory ability as the relative proportion of nestin-positive cells was decreased after 11 days. To further illustrate the negative long-term effects of this ethanol dose, cultures were exposed for 30 days. After this period, virtually no neurons or myelinating oligodendrocytes were present in the ethanol-treated cultures. In conclusion, chronic exposure to ethanol, even at small doses, dramatically and persistently affects normal development.
|
|
| 15. |
- Rogoz, Vladyslav, et al.
(author)
-
High-mass metal ion irradiation enables growth of high-entropy sublattice nitride thin films from elemental targets
- 2023
-
In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : American Vacuum Society. - 0734-2101 .- 1520-8559. ; 41:6
-
Journal article (peer-reviewed)abstract
- Synthesis of high-entropy sublattice nitride (HESN) coatings by magnetron sputtering is typically done using custom-made alloyed targets with specific elemental compositions. This approach is expensive, requires long delivery times, and offers very limited flexibility to adjust the film composition. Here, we demonstrate a new method to grow HESN films, which relies on elemental targets arranged in the multicathode configuration with substrates rotating during deposition. TiVNbMoWN films are grown at a temperature of similar to 520(degrees)C using Ti, V, Nb, and Mo targets operating in the direct current magnetron sputtering mode, while the W target, operated by high power impulse magnetron sputtering (HiPIMS), provides a source of heavy ions. The energy of the metal ions EW+ is controlled in the range from 80 to 620 eV by varying the amplitude of the substrate bias pulses V-s, synchronized with the metal-ion-rich phase of HiPIMS pulses. We demonstrate that W(+ )irradiation provides dynamic recoil mixing of the film-forming components in the near-surface atomic layers. For EW+ >= 320 eV the multilayer formation phenomena, inherent for this deposition geometry, are suppressed and, hence, compositionally uniform HESN films are obtained, as confirmed by the microstructural and elemental analysis.(c) 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license(http://creativecommons.org/licenses/by/4.0/)
|
|
| 16. |
- Sandelin, Martin, et al.
(author)
-
Metastasis-associated S100A4 (Mts1) protein is expressed in subpopulations of sensory and autonomic neurons and in Schwann cells of the adult rat.
- 2004
-
In: J Comp Neurol.. ; 473:2, s. 233-43
-
Journal article (pop. science, debate, etc.)abstract
- S100A4 (Mts1) is a member of a family of calcium-binding proteins of the EF-hand type, which are widely expressed in the nervous system, where they appear to be involved in the regulation of neuron survival, plasticity, and response to injury or disease. S100A4 has previously been demonstrated in astrocytes of the white matter and rostral migratory stream of the adult rat. After injury, S100A4 is markedly up-regulated in affected central nervous white matter areas as well as in the periventricular area and rostral migratory stream. Here, we show that S100A4 is expressed in a subpopulation of dorsal root, trigeminal, geniculate, and nodose ganglion cells; in a subpopulation of postganglionic sympathetic and parasympathetic neurons; in chromaffin cells of the adrenal medulla; and in satellite and Schwann cells. In dorsal root ganglia, S100A4-positive cells appear to constitute a subpopulation of small ganglion neurons, a few of which coexpressed calcitonin gene-related peptide (CGRP) and Griffonia simplicifolia agglutinin (GSA) isolectin B4 (B4). S100A4 protein appears to be transported from dorsal root ganglia to the spinal cord, where it is deposited in the tract of Lissauer. After peripheral nerve or dorsal root injury, a few S100A4-positive cells coexpress CGRP, GSA, or galanin. Peripheral nerve or dorsal root injury induces a marked up-regulation of S100A4 expression in satellite cells in the ganglion and in Schwann cells at the injury site and in the distal stump. This pattern of distribution partially overlaps that of the previously studied S100B and S100A6 proteins, indicating a possible functional cooperation between these proteins. The presence of S100A4 in sensory neurons, including their processes in the central nervous system, suggests that S100A4 is involved in propagation of sensory impulses in specific fiber types. J. Comp. Neurol. 473:233-243, 2004. © 2004 Wiley-Liss, Inc.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Sroba, Viktor, et al.
(author)
-
Cross-ionization of the sputtered flux during hybrid high power impulse/direct-current magnetron co-sputtering
- 2024
-
In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : A V S AMER INST PHYSICS. - 0734-2101 .- 1520-8559. ; 42:2
-
Journal article (peer-reviewed)abstract
- Time-resolved ion mass spectrometry is used to analyze the type and the energy of metal-ion fluxes during hybrid high-power impulse/direct-current magnetron co-sputtering (HiPIMS/DCMS) in Ar. The study focuses on the effect of HiPIMS plasma plumes on the cross-ionization of the material flux sputtered from the DCMS source. Al, Si, Ti, and Hf elemental targets are used to investigate the effect of the metal's first ionization potential IPMe1 and mass on the extent of cross-ionization. It is demonstrated that the interaction with HiPIMS plasma results in the significant ionization of the material flux sputtered from the DCMS source. Experiments conducted with elements of similar mass but having different IPMe1 values, Si and Al (Si-HiPIMS/Al-DCMS and Al-HiPIMS/Si-DCMS) reveal that the ionization of the DCMS flux is favored if the sputtered element has lower ionization potential than the one operating in the HiPIMS mode. If elements having similar IPMe1 are used on both sources, the metal mass becomes a decisive parameter as evidenced by experiments involving Ti and Hf (Ti-HiPIMS/Hf-DCMS and Hf-HiPIMS/Ti-DCMS). In such a case, Ti+ fluxes during Hf-HiPIMS/Ti-DCMS may even exceed Hf+ fluxes from the HiPIMS cathode and are much stronger than Hf+ fluxes during Ti-HiPIMS/Hf-DCMS. The latter effect can be explained by the fact that heavier Hf+ ions require longer transit time from the ionization zone to the substrate, which effectively increases the probability of interaction between the Hf-HiPIMS plasma plume and the Ti-DCMS flux, thereby leading to higher Ti ionization. Thus, the common notion of low ionization levels associated with DCMS has to be revised if DCMS is used together with highly ionized plasmas such as HiPIMS operating at higher peak target currents. These results are particularly important for the film growth in the hybrid configuration with substrate bias pulses synchronized to specific ion types.
|
|
| 20. |
- Svenningsen, Åsa Fex, et al.
(author)
-
Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism
- 2011
-
In: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 58:6, s. 620-624
-
Journal article (peer-reviewed)abstract
- The neurosteroid dehydroepiandrosterone (DHEA) is formed locally in the CNS and has been implicated in several processes essential for CNS function, including control of neuronal survival. An important metabolic pathway for DHEA in the CNS involves the steroid hydroxylase CYP7B1. In previous studies, CYP7B1 was identified as a target for estrogen regulation in cells of kidney and liver. In the current study, we examined effects of estrogens on CYP7B1-mediated metabolism of DHEA in primary cultures of rat astrocytes and co-cultures of rat CNS cells. Astrocytes, which interact with neurons in several ways, are important for brain neurosteroidogenesis. We found that estradiol significantly suppressed CYP7B1-mediated DHEA hydroxylation in primary mixed CNS cultures from fetal and newborn rats. Also, CYP7B1-mediated DHEA hydroxylation and CYP7B1 mRNA were markedly suppressed by estrogen in primary cultures of rat astrocytes. Interestingly, diarylpropionitrile, a well-known agonist of estrogen receptor β, also suppressed CYP7B1-mediated hydroxylation of DHEA. Several previous studies have reported neuroprotective effects of estrogens. The current data indicate that one of the mechanisms whereby estrogen can exert protective effects in the CNS may involve increase of the levels of DHEA by suppression of its metabolism.
|
|
| 21. |
- Wicher, Bartosz, et al.
(author)
-
Carbon ion self-sputtering attained by sublimation of hot graphite target and controlled by pulse injection of a neon-helium gas mixture
- 2023
-
In: Applied Surface Science. - : ELSEVIER. - 0169-4332 .- 1873-5584. ; 620
-
Journal article (peer-reviewed)abstract
- The operation of graphite targets with an increased temperature (HT - hot target) is studied for the case of gas injection magnetron sputtering (GIMS) of: 1) diamond-like carbon (DLC), and 2) carbon-silicon carbide (C-SiC) films. A purposely-thinned graphite target with a reduced thermal conductivity is applied for DLC deposition, extending its high temperature sputtering range up to 1636 degrees C. For the purpose of C-SiC synthesis four sockets with a silicon carbide powder are designed within graphite target. In this approach, the C-SiC target surface can be heated up to 1443 degrees C due to a greater energy input from impulse plasma, in the range 322-932 J. The HT sputtering is energy-controlled by a pulsed injection of a neon-helium gas mixture. High-energy Ne+ and He+ ions extend the length of pulsed GIMS discharge due to the self-sputtering effect observed during the deposition of DLC and C-SiC films. These conditions result in an almost 5-fold increase in the film growth rate (up to 185 nm/min) with respect to the operation with a cold target, which is due to the assisting vapour sublimation from custom-designed graphite-based targets. The temperature boosted HT GIMS discharge, proves to be an efficient tool for reaching relatively high (similar to 35 %) sp(3)-hybridized C content in both carbon-based materials. It also allows for tailoring the energy bandgap of DLC-based optical structure, in the range from 1.7 to 2.75 eV, due to the formation of the (C-C) and (C-O) bonds. Higher content of silicon oxide (SiO2-x) and silicon carbide (SiC) phases (15 - 23 %) in the case of C-SiC films results in hardness increase from 21.8 to 30.1 GPa.
|
|
| 22. |
- Wicher, Bartosz, et al.
(author)
-
Superhard oxidation-resistant Ti1-xAlxBy thin films grown by hybrid HiPIMS/DCMS co-sputtering diboride targets without external substrate heating
- 2024
-
In: Materials & design. - : ELSEVIER SCI LTD. - 0264-1275 .- 1873-4197. ; 238
-
Journal article (peer-reviewed)abstract
- Ti1-xAlxBy films (0.40 <= x <= 0.76, and 1.81 <= y <= 2.03) combining good mechanical properties and high-temperature oxidation resistance are demonstrated. Layers are grown using a hybrid high-power impulse and dc magnetron co-sputtering employing two target configurations (AlB2-HiPIMS/TiB2-DCMS and TiB2-HiPIMS/AlB2-DCMS) and no external substrate heating. Near-stoichiometric B content are achieved by co-sputtering two diboride targets. Time-resolved ion mass spectrometry analyses reveal that the ionization of the DCMS flux (Al) is much higher during TiB2-HiPIMS/AlB2-DCMS. The effect is caused by the difference in the first ionization potentials and the ionization probabilities of sputtered metals and results in lower B/metal ratios in films grown in this configuration. The B/metal ratio in the single-phase Ti1-xAlxBy decreases with increasing Al content, which is explained by the change between angular distribution of Ti and Al atoms. Alloying with Al improves the high-temperature oxidation resistance: the thickness of the oxide-scale forming after 1 h anneal at 800 degrees C decreases more than 15 times upon increasing x from 0.36 to 0.74. Ti1-xAlxBy films with 0.58 <= x <= 0.67 offer the best compromise between high-temperature oxidation resistance and mechanical properties with an average oxide scale thickness 90-180 nm and the hardness of 34-38 GPa.
|
|
| 23. |
- Wicher, Grzegorz, et al.
(author)
-
Adult motor neurons show increased susceptibility to axotomy-induced death in mice lacking clusterin
- 2005
-
In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 21:7, s. 2024-2028
-
Journal article (peer-reviewed)abstract
- Clusterin is a highly conserved, amphiphatic glycoprotein present in most tissues. It has been shown to be involved in the regulation of lipid transportation, clearance of cellular debris from the extracellular space and intracellular signal transduction. Clusterin is markedly up-regulated after neural injury but the functional significance of this response is unclear. Here, we show that clusterin up-regulation is substantially greater in hypoglossal motor neurons after hypoglossal nerve avulsion compared with nerve transection. Quantitative analyses of motor neuron numbers after the same lesions in clusterin(-/-) and clusterin(+/+) mice showed significantly larger numbers of surviving motor neurons in clusterin(+/+) mice. These results suggest that clusterin has a neuroprotective role after axotomy.
|
|
| 24. |
|
|
| 25. |
- Wicher, Grzegorz, 1979-
(author)
-
Clusterin and Megalin in The Spinal Cord
- 2006
-
Doctoral thesis (other academic/artistic)abstract
- Nerve injury induces up-regulation of the chaperone protein clusterin in affected neurons and adjacent astrocytes but the functional significance of this response is unclear. We find that motor neuron survival is significantly greater in clusterin(+/+) compared to (-/-) mice. These results suggest that endogenous expression of clusterin is neuroprotective after nerve injury. However, motor neuron survival in clusterin overexpressing mice was not different from that in wildtype mice. In contrast, treatment of neuronal cultures with clusterin-TAT recombinant protein is neuroprotective, including a positive effect on neuronal network complexity.Since extracellular clusterin complexes are endocytosed after binding to various receptors, we examined the expression of known clusterin binding receptors in the spinal cord. We find that megalin is expressed in the nuclei of two cell populations in the mouse spinal cord: i) oligodendrocytes in late postnatal and adult spinal cord white matter, and ii) transiently (E11-15) in a population of immature astrocytes in the dorsal spinal cord. We find no correlation between clusterin and megalin in the intact or injured spinal cord. However, intranuclear localization of megalin, suggesting signalling properties, is supported by the co-localization with γ-secretase, the enzyme responsible for endodomain cleavage of megalin. Megalin deficient mice display a pronounced deformation of the dorsal part of spinal cord, an almost complete absence of oligodendroglial progenitor cells, and a marked reduction in the population of mature astrocytes at later prenatal developmental stages.Taken together, our findings indicate that megalin is a novel signalling molecule for distinct populations of glial cells in the pre- and postnatal spinal cord. The functional role(s) of megalin is unknown. However, its expression patterns and cellular localization suggest that megalin regulates differentiation of oligodendrocytes and astrocytes in the prenatal spinal cord, as well as the function of myelinating oligodendrocytes in the postnatal spinal cord.
|
|
| 26. |
|
|
| 27. |
- Wicher, Grzegorz, et al.
(author)
-
Developmental expression of IL-33 in the mouse brain
- 2013
-
In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 555, s. 171-176
-
Journal article (peer-reviewed)abstract
- IL-33 has important functions in inflammatory and autoimmune diseases. In the brain, models of experimental encephalomyelitis are accompanied by up-regulation of IL-33 expression, and the cytokine is seen as an amplifier of the innate immune response. Little is known, however, about IL-33 the normal brain in adult life, or during development. We have analyzed the expression of IL-33 in the mouse brain during embryonic and postnatal development. Here we report that IL-33 expression was first detected in the CNS during late embryogenesis. From postnatal day 2 (P2) until P9 the expression increased and was strongest in the cerebellum, pons and thalamus, as well as in olfactory bulbs. Expression of IL-33 then became weaker and declined until P23, and it was not present in the adult brain. Both astrocytes and oligodendrocyte precursors expressed IL-33. The vast majority of IL-33 positive cells in the brain displayed nuclear staining, and this was found to be the case also in vitro, using mixed glial cultures. Our data suggest that IL-33 expression is under tight regulation in the normal brain. Its detection during the first three weeks of postnatal life coincides with important parts of the CNS developmental programs, such as general growth and myelination. This opens the possibility that IL-33 plays a role also in the absence of an inflammatory response.
|
|
| 28. |
|
|
| 29. |
- Wicher, Grzegorz, et al.
(author)
-
Estrogen-mediated regulation of steroid metabolism in rat glial cells; effects on neurosteroid levels via regulation of CYP7B1-mediated catalysis
- 2015
-
In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 145, s. 21-27
-
Journal article (peer-reviewed)abstract
- Many neuroactive steroids, including dehydroepiandrosterone (DHEA), pregnenolone, 27-hydroxycholesterol and 17 beta-estradiol, are known to affect development and function of the brain and nervous system. These and other steroids can undergo tissue and/or cell-specific enzymatic conversions into steroid metabolites. Carefully regulated production of steroids with various physiological effects is important for cells of the nervous system. Astrocytes express many steroidogenic enzymes and are considered important producers of brain steroids. The quantitative roles of different pathways for steroid metabolism in rat astrocytes are not clear. In the current study we examined effects of estrogens on steroid metabolism catalyzed by CYP7B1 and other enzymes in primary cultures of rat astrocytes. The CYP7B1 enzyme, which has been linked to neurodegenerative disease, is involved in the metabolism of several important neurosteroids. In the present study, we found that 7 alpha-hydroxylation, performed by CYP7B1, is the quantitatively most important pathway for DHEA metabolism in rat astrocytes. In addition, our present experiments on catalytic steroid conversions revealed that estrogens significantly suppress the CYP7B1-catalyzed metabolism of not only DHEA but also of pregnenolone and 27-hydroxycholesterol in rat astrocytes. These novel findings point to a regulatory mechanism for control of the cellular levels of these neurosteroids via CYP7B1. Our hypothesis that estrogens can regulate neurosteroid levels via this enzymatic reaction was supported by experiments using ELISA to assay levels of DHEA and pregnenolone in the presence or absence of estrogen. Furthermore, the present results show that estrogen suppresses CYP7B1-catalyzed 7 alpha-hydroxylation also in primary cultures of rat Schwann cells, indicating that regulation by estrogen via this enzyme may be of relevance in both the CNS and the PNS.
|
|
| 30. |
- Wicher, Grzegorz, et al.
(author)
-
Extracellular clusterin promotes neuronal network complexity in vitro
- 2008
-
In: NeuroReport. - 0959-4965 .- 1473-558X. ; 19:15, s. 1487-1491
-
Journal article (peer-reviewed)abstract
- Clusterin (apolipoprotein J), a highly conserved amphiphatic glycoprotein and chaperone, has been implicated in a wide range of physiological and pathological processes. As a secreted protein, clusterin has been shown to act extracellularly where it is involved in lipid transportation and clearance of cellular debris. Intracellularly, clusterin may regulate signal transduction and is upregulated after cell stress. After neural injury, clusterin may be involved in nerve cell survival and postinjury neuroplasticity. In this study, we investigated the role of extracelullar clusterin on neuronal network complexity in vitro. Quantitative analysis of clustrin-treated neuronal cultures showed significantly higher network complexity. These findings suggest that in addition to previously demonstrated neuroprotective roles, clusterin may also be involved in neuronal process formation, elongation, and plasticity.
|
|
| 31. |
|
|
| 32. |
- Wicher, Grzegorz K., et al.
(author)
-
Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury
- 2017
-
In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 34:22, s. 3173-3182
-
Journal article (peer-reviewed)abstract
- Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.
|
|
| 33. |
- Wicher, Grzegorz, et al.
(author)
-
Low-density lipoprotein receptor-related protein (LRP)-2/megalin is transiently expressed in a subpopulation of neural progenitors in the embryonic mouse spinal cord
- 2005
-
In: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 492:2, s. 123-131
-
Journal article (peer-reviewed)abstract
- The lipoprotein receptor LRP2/megalin is expressed by absorptive epithelia and involved in receptor-mediated endocytosis of a wide range of ligands. Megalin is expressed in the neuroepithelium during central nervous system (CNS) development. Mice with homozygous deletions of the megalin gene show severe forebrain abnormalities. The possible role of megalin in the developing spinal cord, however, is unknown. Here we examined the spatial and temporal expression pattern of megalin in the embryonic mouse spinal cord using an antibody that specifically recognizes the cytoplasmic part of the megalin molecule. In line with published data, we show expression of megalin in ependymal cells of the central canal from embryonic day (E)11 until birth. In addition, from E11 until E15 a population of cells was found in the dorsal part of the developing spinal cord strongly immunoreactive against megalin. Double labeling showed that most of these cells express vimentin, a marker for immature astrocytes and radial glia, but not brain lipid binding protein (BLBP), a marker for radial glial cells, or glial fibrillary acidic protein (GFAP), a marker for mature astrocytes. These findings indicate that the majority of the megalin-positive cells are astroglial precursors. Megalin immunoreactivity was mainly localized in the nuclei of these cells, suggesting that the cytoplasmic part of the megalin molecule can be cleaved following ligand binding and translocated to the nucleus to act as a transcription factor or regulate other transcription factors. These findings suggest that megalin has a crucial role in the development of astrocytes of the spinal cord.
|
|
| 34. |
- Wicher, Grzegorz, et al.
(author)
-
Low density lipoprotein-related protein-2/megalin is expressed in oligodendrocytes in the mouse spinal cord white matter
- 2006
-
In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 83:5, s. 864-873
-
Journal article (peer-reviewed)abstract
- Lipoprotein receptor-related protein-2 (LRP2)/megalin is a member of the low density lipoprotein receptor (LDLR) family, and is essential in absorptive epithelia for endocytosis of lipoproteins, low molecular weight proteins, cholesterol and vitamins, as well as in cellular signaling. Previous studies have shown megalin expression in ependymal cells and choroid plexus. We have investigated megalin expression in the spinal cord of postnatal mice with immunohistochemistry and immunoblot. Antibodies recognizing either the cytoplasmic tail (MM6) or the extracellular domain (E11) of megalin labeled oligodendrocytes in the spinal cord white matter, in parallel with myelination. MM6 antibodies, predominantly labeled the nuclei, whereas E11 antibodies labeled the cytoplasm of these cells. MM6 antibodies labeled also nuclei of oligodendrocytes cultured from embryonic mouse spinal cord. Immunoblots of spinal cord showed intact megalin, as well as its carboxyterminal fragment, the part remaining after shedding of the extracellular domain of megalin. Megalin-immunoreactive oligodendrocytes also expressed presenilin 1, an enzyme responsible for gamma-secretase mediated endodomain cleavage. These findings show that spinal cord oligodendrocytes are phenotypically different from those in the brain, and indicate that megalin translocates signals from the cell membrane to the nucleus of oligodendrocytes during the formation and maintenance of myelin of long spinal cord pathways.
|
|
| 35. |
- Wicher, Grzegorz, et al.
(author)
-
Megalin deficiency induces critical changes in early glial development in mouse spinal cord
- 2008
-
In: NeuroReport. - 0959-4965 .- 1473-558X. ; 19:5, s. 559-563
-
Journal article (peer-reviewed)abstract
- Low density lipoprotein receptor-related protein, megalin, is a multifunctional lipoproptein receptor expressed by absorptive epithelia for endocytosis of numerous ligands. Megalin is widely expressed during embryonic life and is essential for development of the nervous system as evidenced by severe forebrain abnormalities in megalin (-/-). Here, we investigated the influence of megalin deficiency on prenatal spinal cord development in mice. In contrast to wild-type mice, cells expressing Olig2 and NG2, that is, oligodendroglial precursor cells, are absent from embryonic stage E16 in megalin (-/-) mice. At the end of prenatal development, there is a failure in vertebral development, and the number of astrocytes are markedly reduced in megalin (-/-) mice. These findings indicate that megalin is essential in astro-oligodendroglial interactions during development of the spinal cord.
|
|
| 36. |
- Wu, Zhigang, et al.
(author)
-
Microfluidic high viability neural cell separation using viscoelastically tuned hydrodynamic spreading
- 2008
-
In: Biomedical microdevices (Print). - : Springer Science and Business Media LLC. - 1387-2176 .- 1572-8781. ; 10:5, s. 631-638
-
Journal article (peer-reviewed)abstract
- A high viability microfluidic cell separation technique of high throughput was demonstrated based on size difference continuous mode hydrodynamic spreading with viscoelastic tuning. Using water with fluorescent dye as sample fluid and in parallel introducing as elution a viscoelastic biocompatible polymer solution of alginic sodium, the spreading behavior was investigated at different polymer concentrations and flow rates. Particle separation was studied in the same detail for 9.9 mu m and 1.9 mu m latex beads. Using buffered aqueous solutions and further surface treatments to protect from cell adhesion, separation between neuron cells and glial cells from rat's spine cord was demonstrated and compared to the separation of latex particles of 20 and 4.6 mu m sizes. High relative viability (above 90%) of neural cells was demonstrated compared the reference cells of the same batch.
|
|
| 37. |
- Wu, Zhigang, et al.
(author)
-
Microfluidic high viability separation of neural cells
- 2009
-
In: 2009 4TH IEEE INTERNATIONAL CONFERENCE ON NANO/MICRO ENGINEERED AND MOLECULAR SYSTEMS, VOLS 1 AND 2, Shenzhen, CHINA, JAN 05-08, 2009. - : IEEE. - 9781424446292 ; , s. 1079-1083
-
Conference paper (peer-reviewed)abstract
- A novel microfluidic platform is presented for sorting by size dissociated neurons, glia and stem cells from biopsies of the central nerve system. A highly biocompatible aqueous polymer solution was used in hydrodynamic spreading controlled cell separation. Before cell separation, particles were used for demonstration. To verify the results the fractions were studied using flow cytometry. Further, they were cultured and differentiated. The study indicated that the technique is ready for biological study and that it has a high potential for applications in neural cell regeneration therapy.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Xie, Yuan, et al.
(author)
-
The Human Glioblastoma Cell Culture Resource : Validated Cell Models Representing All Molecular Subtypes
- 2015
-
In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 2:10, s. 1351-1363
-
Journal article (peer-reviewed)abstract
- Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called gliomastem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional sub-types. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.
|
|
