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21.
Juliana M Sousa-Canavez Flavio C Canavez Kátia RM Leite Luiz H Camara-Lopes 《Genetic vaccines and therapy》2008,6(1):1-7
Background
Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.Methods
Enhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.Results
Experiments confirm that electroporation alone is more effective in enhancing reporter gene expression than plasmid injection alone, plasmid conjugation with liposomes followed by injection, or than the combination of liposomes and electroporation. However, with two time courses of multiple electrically-mediated plasmid deliveries, neither the levels nor duration of transgene expression are significantly increased. Tissue damage may increase following a second treatment, no further damage is observed after a third treatment. When electroporation conditions utilized in a mouse model are tested in thicker rat skin, only higher field strengths or longer pulses were as effective in plasmid delivery.Conclusion
Electroporation enhances reporter plasmid delivery to the skin to a greater extent than the liposome conjugation method tested. Multiple deliveries do not necessarily result in higher or longer term expression. In addition, some impact on tissue integrity with respect to surface damage is observed. Pulsing conditions should be optimized for the model and for the expression profile desired. 相似文献22.
Mariana A Antunes Soraia C Abreu Fernanda F Cruz Ana Clara Teixeira Miquéias Lopes-Pacheco Elga Bandeira Priscilla C Olsen Bruno L Diaz Christina M Takyia Isalira PRG Freitas Nazareth N Rocha Vera L Capelozzi Débora G Xisto Daniel J Weiss Marcelo M Morales Patricia RM Rocco 《Respiratory research》2014,15(1)
We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. 相似文献
23.
Seasonal flooding,topography, and organic debris interact to influence the emergence and distribution of seedlings in a tropical grassland
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Francielli Bao Tracy Elsey‐Quirk Marco Antonio de Assis Rafael Arruda Arnildo Pott 《Biotropica》2018,50(4):616-624
In seasonally flooded wetlands, inundation and associated organic debris deposition followed by a drawdown period can promote plant community diversity across space and time. Post‐flood regeneration might be influenced by the direct effect of flooding on seed dispersal and seedling emergence, as well as the indirect effect of organic debris on seed trapping and germination. Our objective was to examine the influence of seasonal flooding, topography, and organic debris cover on seedling distribution in a seasonally flooded grassland. We measured species richness, seedling abundance, and organic debris cover for 3 yr in a seasonally flooded grassland in the Pantanal, Brazil, at three topographic levels at the end of the flood season and during the dry season when there was no debris deposition. A total of 43 species were recorded, with no difference in species richness detected between seasons. However, the abundance of some species was higher post‐flood than during the dry period. The greatest seedling abundance and richness were found post‐flood at intermediate elevations, followed by high and the lowest elevations. Seed germination and seedling establishment were likely suppressed at low topographic positions due to shading from organic debris and poor drainage. Therefore, areas with predictable annual floods promote diversity by creating spatial and temporal variations in environmental conditions. 相似文献
24.
Selenium unmasks protective iron armor: A possible defense against cutaneous inflammation and cancer
Jack L. Arbiser Michael Y. Bonner Nicole Ward Justin Elsey Shikha Rao 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2518-2527
Background
A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes.Methods
We analyze and compare gene expression profiles in the GEO database from clinical skin samples taken from healthy patients and psoriasis patients (both involved and noninvolved skin lesions). We validated the gene expression results against a second, independent, cohort from the GEO database.Results
Significant reduction in gene expression of GPX4, elevated expression of Nrf2 downstream targets, and expression profiles mirroring erastin-inhibition of Cystine/Glutamate Antiporter-System XC activity in psoriatic skin lesions, compared to both noninvolved skin and healthy patient samples, suggest an innately inducible mechanism of ferroptosis.Conclusions
We present data that may indicate selenoproteins, particularly GPX4, in resolving inflammation and skin cancer, including the novel hypothesis that the human organism may downregulate GPX4 and reactive oxygen (REDOX) regulating proteins in the skin as a way of resolving psoriasis and nonmelanoma skin cancer through increased reactive oxygen species. Further studies are needed to investigate ferroptosis as a possible physiologic mechanism for eliminating inflammatory and malignant tissues.General significance
This study provides a fresh framework for understanding the seemingly contradictory effects of selenium supplementation. In addition, it offers a novel explanation of how physiologic upregulation of ferroptosis and downregulation of selenoprotein synthesis may mediate resolution of inflammation and carcinogenesis. This is of therapeutic significance. 相似文献25.
Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks
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Shin‐ichiro Hiraga Chandre Monerawela Yuki Katou Sophie Shaw Kate RM Clark Katsuhiko Shirahige Anne D Donaldson 《EMBO reports》2018,19(9)
Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome‐wide binding of budding yeast Rif1 by chromatin immunoprecipitation, during G1 phase and in S phase with replication progressing normally or blocked by hydroxyurea. Rif1 associates strongly with telomeres through interaction with Rap1. By comparing genomic binding of wild‐type Rif1 and truncated Rif1 lacking the Rap1‐interaction domain, we identify hundreds of Rap1‐dependent and Rap1‐independent chromosome interaction sites. Rif1 binds to centromeres, highly transcribed genes and replication origins in a Rap1‐independent manner, associating with both early and late‐initiating origins. Interestingly, Rif1 also binds around activated origins when replication progression is blocked by hydroxyurea, suggesting association with blocked forks. Using nascent DNA labelling and DNA combing techniques, we find that in cells treated with hydroxyurea, yeast Rif1 stabilises recently synthesised DNA. Our results indicate that, in addition to controlling DNA replication initiation, budding yeast Rif1 plays an ongoing role after initiation and controls events at blocked replication forks. 相似文献
26.
Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c 总被引:3,自引:1,他引:2
Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial
genome, exhibits one of the most heterogeneous rates of amino acid
replacement among placental mammals. Moreover, it has been demonstrated
that cytochrome c oxidase has undergone a structural change in higher
primates which has altered its physical interaction with cytochrome c. We
collected a large data set of COII sequences from several orders of mammals
with emphasis on primates, rodents, and artiodactyls. Using phylogenetic
hypotheses based on data independent of the COII gene, we demonstrated that
an increased number of amino acid replacements are concentrated among
higher primates. Incorporating approximate divergence dates derived from
the fossil record, we find that most of the change occurred independently
along the New World monkey lineage and in a rapid burst before apes and Old
World monkeys diverged. There is some evidence that Old World monkeys have
undergone a faster rate of nonsynonymous substitution than have apes. Rates
of substitution at four-fold degenerate sites in primates are relatively
homogeneous, indicating that the rate heterogeneity is restricted to
nondegenerate sites. Excluding the rate acceleration mentioned above,
primates, rodents, and artiodactyls have remarkably similar nonsynonymous
replacement rates. A different pattern is observed for transversions at
four-fold degenerate sites, for which rodents exhibit a higher rate of
replacement than do primates and artiodactyls. Finally, we hypothesize
specific amino acid replacements which may account for much of the
structural difference in cytochrome c oxidase between higher primates and
other mammals.
相似文献
27.
Relationships among msx gene structure and function in zebrafish and other vertebrates 总被引:6,自引:2,他引:4
Ekker M; Akimenko MA; Allende ML; Smith R; Drouin G; Langille RM; Weinberg ES; Westerfield M 《Molecular biology and evolution》1997,14(10):1008-1022
The zebrafish genome contains at least five msx homeobox genes, msxA, msxB,
msxC, msxD, and the newly isolated msxE. Although these genes share
structural features common to all Msx genes, phylogenetic analyses of
protein sequences indicate that the msx genes from zebrafish are not
orthologous to the Msx1 and Msx2 genes of mammals, birds, and amphibians.
The zebrafish msxB and msxC are more closely related to each other and to
the mouse Msx3. Similarly, although the combinatorial expression of the
zebrafish msx genes in the embryonic dorsal neuroectoderm, visceral arches,
fins, and sensory organs suggests functional similarities with the Msx
genes of other vertebrates, differences in the expression patterns preclude
precise assignment of orthological relationships. Distinct duplication
events may have given rise to the msx genes of modern fish and other
vertebrate lineages whereas many aspects of msx gene functions during
embryonic development have been preserved.
相似文献
28.
29.
Surface structure changes of rat adipocytes during lypolysis stimulated by various lypolysis stimulated by various lypolytic agents
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A qualitative and quantitative electron microscopic study was performed on rat adipocytes during stimulation of lipolysis by various agents. Scanning electron microscopy of control cells revealed a spherical cell with a textured glycocalyx surface exhibiting small irregular projections. Globular surface evaginations or protrusions measuring 8-18 μM in diameter were seen on cell hemispheres, and there was an average of one protrusion for every two hemispheres examined. Distribution analysis showed that 60 percent of the hemispheres had no protrusions, and 25, 10, and 5 percent of the hemispheres had one, two or three protrusions, respectively. Thin-section and freeze- fracture electron microscopy of the protrusions showed a small triglyceride droplet surrounded by a thin cytoplasmic rim that was continuous with the main cytoplasmic matrix. The glycocalyx coating and plasma membrane extended from the cell surface onto, and over, the protrusion. Scanning microscopy of cells stimulated by lipolytic agents, including epinephrine, adrenocorticotropic hormone, theophylline, and dibutyryl cyclic AMP, revealed a dose-dependent increase in the number of protrusions per cell hemisphere. Maximal concentrations of lipolytic hormones cuase an average 2.5-fold increase in the number of protrusions per hemisphere without changing the average size of the protrusions. Only 40 percent of the stimulated cell hemispheres exhibited no protrusions; over 15 percent of the cells contained three or more; and a number of the protrusions were multilobulate. Insulin prevented the increase in the number of protrusions and the change in distribution caused by the lipolytic hormones but did not prevent the increase caused by theophylline and dibutryl cyclic AMP. The data suggest that the protrusions are a structural feature of the cell and may be related to the lypolytic pathway. These observations may help explain some of the discrepant biochemical data relating to hormonal stimulation of lipolysis. 相似文献
30.
Mark Merchant Stephanie Williams Phillip L Trosclair Ruth M Elsey Kaili Mills 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,148(4):921-925
Temperature probes were inserted into the stomachs of juvenile American alligators (Alligator mississippiensis) maintained outdoors at ambient fluctuating temperatures. Internal body temperatures (T(b)) were measured every 15 min for two days, and then the alligators were injected with bacterial lipopolysaccharide (LPS), pyrogen-free saline, or left untreated. Alligators injected intraperitoneally with LPS exhibited maximum T(b)s 2.6+/-1.1 degrees C and 3.5+/-1.2 degrees C higher than untreated control animals on days one and two after treatment, respectively. T(b)s for these animals fell to within control ranges by day three postinjection. Similarly, mean preferred body temperatures (MPBTs) were significantly higher for LPS-injected alligators on days one (4.2+/-1.8 degrees C) and two (3.5+/-1.6 degrees C) after treatment. Intraperitoneal injection of heat-killed Aeromonas hydrophila, a gram-negative bacterium known to infect crocodilians, resulted in a fever while injection of Staphylococcus aureus (gram positive) did not elicit a febrile response. Injection of LPS in alligators maintained indoors in a constant temperature environment resulted in no increase in internal T(b). These results indicate that alligators did not exhibit a febrile response in the absence of a thermal gradient, and suggest that febrile responses observed are probably behavioral in nature. 相似文献