Microglia are the immune cells of the central nervous system involved in a variety of developmental processes, such as regulation of cell death and survival, spatial patterning, and contribute to the development of Purkinje cells (PCs) during migration. Microglia express immunoglobulin G Fc receptors (FcgRs). In this report, we describe microglial FcgR expression and its relation to abnormal PC migration in the cerebellum during development. To detect microglial FcgR, the direct anti-IgG (secondary antisera) and high concentrations of Triton X-100 were applied as a method for labeling microglial cells without the use of any specific primary antiserum. By using Acp2?/? mice, which show an excessive PC migration into the molecular layer (ml), and 3 different types of mice with a null to alter the Reelin pathway (Reeler-, Dab1 (SCM)-, and Apoer mutant mice), we studied the location of PCs and the expression of FcgRs. Wild type littermates were used as controls in all studies. We show that the expression of microglial FcgRs was absent and PCs were ectopically located in the white matter in the cerebella of all mutant mice, except for the Acp2?/? mice (PCs were located in the ml). These results suggest a role for FcgRs in the Reelin signaling pathway, not in regulating PC migration, but rather in the adaptation to an environment with a relatively large number of ectopically located PCs. However, the exact correlation between the ectopic location of PCs and lack of FcgRs in Reeler, SCM, and Apoer?/? mice and the presence of FcgRs and directed PC location in the ml in Acp2?/? mice are yet to be determined.
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by the presence of filamentous inclusions in nerve cells. These filaments are amyloid fibrils that are made of the protein α-synuclein, which is genetically linked to rare cases of PD and DLB. β-Synuclein, which shares 60% identity with α-synuclein, is not found in the inclusions. Furthermore, while recombinant α-synuclein readily assembles into amyloid fibrils, β-synuclein fails to do so. It has been suggested that this may be due to the lack in β-synuclein of a hydrophobic region that spans residues 73-83 of α-synuclein. Here, fibril assembly of recombinant human α-synuclein, α-synuclein deletion mutants, β-synuclein and β/α-synuclein chimeras was assayed quantitatively by thioflavin T fluorescence and semi-quantitatively by transmission electron microscopy. Deletion of residues 73-83 from α-synuclein did not abolish filament formation. Furthermore, a chimera of β-synuclein with α-synuclein(73-83) inserted was significantly less fibrillogenic than wild-type α-synuclein. These findings, together with results obtained using a number of recombinant synucleins, showed a correlation between fibrillogenesis and mean β-strand propensity, hydrophilicity and charge of the amino acid sequences. The combination of these simple physicochemical properties with a previously described calculation of β-strand contiguity allowed us to design mutations that changed the fibrillogenic propensity of α-synuclein in predictable ways. 相似文献
Nuclear pore complexes (NPCs) are supramolecular nanomachines that mediate the exchange of macromolecules and inorganic ions between the nucleus and the cytosol. Although there is no doubt that large cargo is transported through the centrally located channel, the route of ions and small molecules remains debatable. We thus tested the hypothesis that there are two separate pathways by imaging NPCs using atomic force microscopy, NPC electrical conductivity measurements, and macromolecule permeability assays. Our data indicate a spatial separation between the active transport of macromolecules through the central channel and the passive transport of ions and small macromolecules through the pore periphery. 相似文献
In order to examine the systematic application of seed-coat microsculpturing in Isatis, seed surfaces of 23 species (41 populations) in four genera of tribe Isatideae were examined using scanning electron microscopy (SEM). Eight types of basic ornamentation patterns were recognized among the studied specimens. Of these, the reticulate–areolate type was the most common and was found in the genera Isatis, Pachypterygium, Samerari and Tauscheria and 15 species (e.g., I. cappodocica, I. kotschyana and I. tinctoria). The reticulate type, the second most frequent, occurred in 7 species while other types each were represented by only one or 2 species. Although different populations of a given species show similar seed-surface sculpturing in most cases, in some polymorphic species like I. cappadocica and I. kotschyana these patterns were variable among populations. To some extent the variation corresponds to infraspecific taxa for some species, but the differences are not significant enough to be useful in the delimitation of the subspecies recognized by previous workers. Moreover, seed-coat characters do not support the separation of genera Isatis, Pachypterygium, Sameraria and Tauscheria. 相似文献
Excessive drinking of alcohol has been frequently associated with gastric injury; however, its underlying molecular mechanisms have been inadequately investigated. Methyl palmitate (MP) has demonstrated marked hepato-, cardio- and pulmonary protective features; however, its effects on ethanol-induced gastric injury have not been studied. The aim of the present study was to evaluate the potential gastroprotective activity of MP against ethanol-evoked gastric mucosal damage in rats and associated molecular mechanisms, for example, mitogen-activated protein kinases (MAPKs), nuclear factor κB (NF-κB), and phosphoinositide 3 kinase/protein kinase B (PI3K/AKT) pathways. The rat stomachs were examined in terms of the inflammatory, oxidative, and apoptotic perturbations. Current data demonstrated that pretreatment with MP attenuated the gross gastric damage, scores of ulcer index, area of mucosal lesions and histopathology outcomes; actions which were similar to the reference antiulcer omeprazole. MP inhibited NF-κB expression, its nuclear translocation, and the expression of its downstream signals, for example, tumor necrosis factor-α and myeloperoxidase besides restoration of interleukin-10 levels. Western blot analysis revealed that MP counteracted the disruption of MAPKs signaling via lowering p-c-Jun N-terminal kinase 1/2 (p-JNK1/2) expression and restoring the phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) levels without affecting p-p38MAPK levels. Additionally, MP improved the antioxidant milieu via diminishing lipid peroxides and enhancing glutathione, glutathione peroxidase, total antioxidant capacity and mucosal nitric oxide. In the context of apoptosis, MP inhibited the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP) and Bax protein expression with upregulating B cell lymphoma-2 expression (Bcl-2), thus, promoting gastric cellular survival. This was confirmed by MP activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K p110α and p-AKT. Together, the present findings report the gastroprotective actions of MP mediated via its anti-inflammatory, antioxidant, and antiapoptotic actions. The underlying molecular mechanisms involve, at least partly, the modulation of MAPKs, NF-κB and PI3K/AKT transduction. 相似文献
The aim of this study was to assess the efficacy of resveratrol (Res) on radiosensitivity of 5-fluorouracil (5-FU) in the spheroid culture of MCF-7 breast cancer cell line using colony formation examination. Spheroids on day 9 with 300 µm diameters were treated with 20 µM resveratrol and/or 1 µM 5-FU for one volume doubling time (VDT) (42 hours) and then irradiated with 2 Gy gamma radiation (60Co) in various groups. Then the viability of the cells and clonogenic ability were acquired by blue dye exclusion and colony formation assay, respectively. The population doubling time in the monolayer culture and the VDT of spheroid culture was 22.48 0.23 hours and 42 0.63 hours respectively. None of the drugs and combination of them had any effect on the viability of cells. The combination treatment of 5-FU+Res+ radiation significantly reduced the colony formation ability of spheroid cells in comparison with each treatment alone. Our results indicated that resveratrol can significantly decrease colony number of breast cancer spheroid cells treated with 5-FU in combination with gamma-rays. Thus, resveratrol as a hypoxia-inducible factor-1-alpha inhibitor increased the radiosensitization of breast cancer spheroid cells. 相似文献
Bioprocess and Biosystems Engineering - In bubble column bioreactors, the hydrodynamic behavior like mixing time, bubble size and morphology of filamentous fungi are influenced by the construction... 相似文献
This study was conducted to reveal genetic diversity among 23 local apple genotypes using nuclear (RAPD) and chloroplast DNA (PCR-cpRFLP) markers. Eleven RAPD primers and four cpDNA primer combinations were used in this study. RAPD primers produced a total of 77 polymorphic fragments with an average of seven bands per primer. The percentage of polymorphic bands (68.14 %) showed the efficiency of used RAPD primers in distinguishing all the genotypes considered. Genetic similarity between studied genotypes varied from 0.38 to 0.72 and cluster analysis showed the abundant diversity, indicating high intraspecific genetic variation between Iranian apple genotypes. From the four universal chloroplast primer pairs, three primer pairs amplified the fragments and their combinations showed polymorphic patterns and revealed intraspecific chloroplast variation. The information will facilitate germplasm identification, conservation and new cultivar development. 相似文献
We hypothesized that associations among plant functional traits may differ within different ecological assemblages and plant communities. Association among plant traits including plant maximum height, seed weight, fruit type, pollination mode, mean leaf area, and leaf type were explored within life forms, plant strategy groups along with lowland and montane forest vegetation. In total, 83 sampling plots of 400 m2 were placed along a 2400 m altitudinal gradient in Hyrcanian forest. Importance‐values of species within vegetation types were used for weighting data and trait associations were explored using categorical principal component analysis. A G‐test and Fisher's exact test of independence were used to retest significance of the correlations. Different paired trait associations (association lines) including height–leaf, height–seed, height–pollination, leaf–seed, seed–fruit and fruit–pollination were observed and their ecological or physiological basis was discussed. Life forms, strategy types and vegetation types differed based on association lines. Some of the well‐known trade‐offs appear by increasing scale from ecological groups to vegetation types in Hyrcanian forest. The observed patterns of trait associations in Hyrcanian forest and several other ecosystems of the world call the generality of previously accepted trait correlations into question. 相似文献