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91.
Korotkova M Ohlsson C Gabrielsson B Hanson LA Strandvik B 《Biochimica et biophysica acta》2005,1724(3):248-254
Electropermeabilization designates the use of electric pulses to overcome the barrier of the cell membrane. This physical method is used to transfer anticancer drugs or genes into living cells. Its mechanism remains to be elucidated. A position-dependent modulation of the membrane potential difference is induced, leading to a transient and reversible local membrane alteration. Electropermeabilization allows a fast exchange of small hydrophilic molecules across the membrane. It occurs at the positions of the cell facing the two electrodes on an asymmetrical way. In the case of DNA transfer, a complex process is present, involving a key step of electrophoretically driven association of DNA only with the destabilized membrane facing the cathode. We report here at the membrane level, by using fluorescence microscopy, the visualization of the effect of the polarity and the orientation of electric pulses on membrane permeabilization and gene transfer. Membrane permeabilization depends on electric field orientation. Moreover, at a given electric field orientation, it becomes symmetrical for pulses of reversed polarities. The area of cell membrane where DNA interacts is increased by applying electric pulses with different orientations and polarities, leading to an increase in gene expression. Interestingly, under reversed polarity conditions, part of the DNA associated with the membrane can be removed, showing some evidence for two states of DNA in interaction with the membrane: DNA reversibly associated and DNA irreversibly inserted. 相似文献
92.
Tabary O Corvol H Boncoeur E Chadelat K Fitting C Cavaillon JM Clément A Jacquot J 《American journal of physiology. Lung cellular and molecular physiology》2006,290(3):L588-L596
Persistent presence of PMN in airways is the hallmark of CF. Our aim was to assess PMN adherence, percentage of apoptotic airway PMN (aPMN), and IL-6 and IL-8 production when aPMN are in contact with airway epithelial cells. Before coculture, freshly isolated CF aPMN have greater spontaneous and TNF-alpha-induced apoptosis compared with blood PMN from the same CF patients and from aPMN of non-CF patients. We then examined cocultures of PMN isolated from CF and non-CF airways with bronchial epithelial cells bearing mutated cftr compared with cftr-corrected bronchial epithelial cells. After 18-h coculture, the number of CF aPMN adhered on cftr-deficient bronchial epithelial cells was 2.3-fold higher compared with the coculture of non-CF aPMN adhered on cftr-corrected bronchial epithelial cells. The percentage of CF apoptotic aPMN (9.5 +/- 0.2%) adhered on cftr-deficient bronchial epithelial cells was similar to the percentage of non-CF apoptotic aPMN adhered on cftr-corrected bronchial epithelial cells (10.3 +/- 0.7%). IL-6 and IL-8 levels were enhanced 6.5- and 2.9-fold, respectively, in coculture of CF aPMN adhered on cftr-deficient bronchial epithelial cells compared with coculture of non-CF aPMN adhered on cftr-corrected bronchial epithelial cells. Moreover, blocking surface adhesion molecules ICAM-1, VCAM-1, and E-selectin on cftr-deficient bronchial epithelial cells with specific MAbs inhibited the adherence of CF aPMN by 64, 51, and 50%, respectively. Our data suggest that in CF patients a high number of nonapoptotic PMN adhered on airway epithelium associated with elevated IL-6 and IL-8 levels may contribute to sustained and exaggerated inflammatory response in CF airways. 相似文献
93.
94.
More than 109 base pairs of the genome in higher eucaryotes are positioned in the interphase nucleus such that gene activation, gene repression,
remote gene regulation by enhancer elements, and reading as well as adjusting epigenetic marks are possible. One important
structural and functional component of chromatin organization is the zinc finger factor CTCF. Two decades of research has
advanced the understanding of the fundamental role that CTCF plays in regulating such a vast expanse of DNA. 相似文献
95.
The epigenetic progenitor origin of human cancer 总被引:16,自引:0,他引:16
Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention. 相似文献
96.
Microbial community dynamics within the fast sea ice of Prydz Bay (68°S?78°E) were investigated over an annual cycle at two sites (1 and 3?km offshore) between April and November 2008. There are few long-term sea ice studies, and few that cover the phase of winter darkness when autotrophic processes are curtailed. Mean chlorophyll a concentrations in the ice column ranged between 0.76 and 44.8?μg?L?1 at the 1-km site (Site 1) and 3.11–144.6?μg?L?1 at the 3-km site (Site 2). Highest chlorophyll a usually occurred at the base of the ice. Bacterial concentrations ranged between 0.30 and 2.08?×?108?cells?L?1, heterotrophic nanoflagellates (HNAN) between 0.21?×?105 and 2.98?×?105?cells?L?1 and phototrophic nanoflagellates (PNAN) 0–1.06?×?105?cells?L?1. While HNAN occurred throughout the year, PNAN were largely absent in winter. Dinoflagellates were a conspicuous and occasionally an abundant element of the community (maximum 17,460?cells?L?1), while ciliates were sparse. The bacterial community showed considerable morphological diversity with a dominance of filamentous forms. Bacterial production continued throughout the year ranging between 0 and 22.92?μg?C?L?1?day?1 throughout the ice column. Lowest rates occurred between late June and early August. The sea ice sustained an active and diverse microbial community through its annual extent. The data suggest that during winter darkness the microbial community is dominated by heterotrophic processes, sustained by a pool of dissolved organic carbon. 相似文献
97.
98.
Giedre Motuzaite-Matuzeviciute Harriet V. Hunt Martin K. Jones 《Vegetation History and Archaeobotany》2012,21(1):69-77
The dimensions of archaeobotanical grains identified as Panicum miliaceum (broomcorn millet) vary greatly in size. This is illustrated by the remains from the archaeological site of Zanovskoe in
eastern Ukraine (5th–1st centuries cal. b.c.). We carried out experimental work on broomcorn millet plants and grains, aiming at a comprehensive understanding of factors
that may have contributed to variation in the grain size of broomcorn millet in archaeobotanical assemblages. We analyzed
the dependence of grain size variation on selected environmental and taphonomic factors. Our results indicate that immaturity
is more likely than environmental stress to account for small grain size in broomcorn millet plants. Depending on charring
temperature and time, immature broomcorn millet grains can withstand charring and are potentially preserved in archaeological
assemblages. Depending on maturity level, such grains vary in size and shape. These results are potentially important for
accurate identification of archaeobotanical specimens. 相似文献
99.
Byakika-Kibwika P Lamorde M Mayito J Nabukeera L Mayanja-Kizza H Katabira E Hanpithakpong W Obua C Pakker N Lindegardh N Tarning J de Vries PJ Merry C 《Malaria journal》2012,11(1):132
ABSTRACT: BACKGROUND: Severe malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria. METHODS: Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134). RESULTS: All study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8-24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020-164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290-111256) ngh/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670-9530) ng/mL, with Tmax of 0.14 (0.6 - 6.07) hours and T1/2 of 1.31 (0.8-2.8) hours. Dihydroartemisinin AUC was 3492 (2183-6338) ngh/mL. None of the participants reported adverse events. CONCLUSIONS: Plasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events. 相似文献
100.
Juliet Ndibazza Harriet Mpairwe Emily L. Webb Patrice A. Mawa Margaret Nampijja Lawrence Muhangi Macklyn Kihembo Swaib A. Lule Diana Rutebarika Barbara Apule Florence Akello Hellen Akurut Gloria Oduru Peter Naniima Dennison Kizito Moses Kizza Robert Kizindo Robert Tweyongere Katherine J. Alcock Moses Muwanga Alison M. Elliott 《PloS one》2012,7(12)