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191.
Mia F. Tazi Duaa A. Dakhlallah Kyle Caution Madelyn M. Gerber Sheng-Wei Chang Hany Khalil 《Autophagy》2016,12(11):2026-2037
Cystic fibrosis (CF) is a fatal, genetic disorder that critically affects the lungs and is directly caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR function. Macroautophagy/autophagy is a highly regulated biological process that provides energy during periods of stress and starvation. Autophagy clears pathogens and dysfunctional protein aggregates within macrophages. However, this process is impaired in CF patients and CF mice, as their macrophages exhibit limited autophagy activity. The study of microRNAs (Mirs), and other noncoding RNAs, continues to offer new therapeutic targets. The objective of this study was to elucidate the role of Mirs in dysregulated autophagy-related genes in CF macrophages, and then target them to restore this host-defense function and improve CFTR channel function. We identified the Mirc1/Mir17-92 cluster as a potential negative regulator of autophagy as CF macrophages exhibit decreased autophagy protein expression and increased cluster expression when compared to wild-type (WT) counterparts. The absence or reduced expression of the cluster increases autophagy protein expression, suggesting the canonical inverse relationship between Mirc1/Mir17-92 and autophagy gene expression. An in silico study for targets of Mirs that comprise the cluster suggested that the majority of the Mirs target autophagy mRNAs. Those targets were validated by luciferase assays. Notably, the ability of macrophages expressing mutant F508del CFTR to transport halide through their membranes is compromised and can be restored by downregulation of these inherently elevated Mirs, via restoration of autophagy. In vivo, downregulation of Mir17 and Mir20a partially restored autophagy expression and hence improved the clearance of Burkholderia cenocepacia. Thus, these data advance our understanding of mechanisms underlying the pathobiology of CF and provide a new therapeutic platform for restoring CFTR function and autophagy in patients with CF. 相似文献
192.
We have developed a powerful experimental framework that combines competitive selection and microarray-based genetic footprinting to comprehensively reveal the genetic basis of bacterial behaviors. Application of this method to Escherichia coli motility identifies 95% of the known flagellar and chemotaxis genes, and reveals three dozen novel loci that, to varying degrees and through diverse mechanisms, affect motility. To probe the network context in which these genes function, we developed a method that uncovers genome-wide epistatic interactions through comprehensive analyses of double-mutant phenotypes. This allows us to place the novel genes within the context of signaling and regulatory networks, including the Rcs phosphorelay pathway and the cyclic di-GMP second-messenger system. This unifying framework enables sensitive and comprehensive genetic characterization of complex behaviors across the microbial biosphere. 相似文献
193.
Asfour IA El-Tehewi MM Ahmed MH Abdel-Sattar MA Moustafa NN Hegab HM Fathey OM 《Biological trace element research》2009,127(3):200-210
The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis
of lymphoma cells in patients with non-Hodgkin’s lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided
into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg−1 day−1 for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of
diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage
of apoptotic lymphoma cells after therapy in group II (78.9 ± 13.3% versus 58.9 ± 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in
percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone
marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and
no reduction in CEF in patients who received sodium selenite ‘group II’, denoting the cardioprotective effect of selenium.
It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy
in inducing apoptosis and, consequently, could improve clinical outcome. 相似文献
194.
For many taxa, species are defined by the morphologies of reproductive structures. In many odonates, these structures are the cerci of males (used to hold females during mating) and the thoracic plates of females where the male cerci contact the females' bodies. A previous study showed that the shapes of cerci of Enallagma males (Zygoptera: Coenagrionidae) are best explained by an evolutionary model of punctuated change at the time of speciation, with a homogeneous rate of change across the entire phylogeny of the genus. In the present study, we examine the evolution of shape change in the corresponding female plates. We found that, like male cerci, the shapes of Enallagma female thoracic plates could best be explained by an evolutionary model of punctuated change at the time of speciation, with a homogeneous rate of change across the clade. Moreover, the evolutionary contrasts quantifying the rates of change in male cerci and female thoracic plates were positively related across the history of the clade, demonstrating that these male and female structures evolve in a correlated fashion. This pattern of evolution suggests that these structures are primary signals of species identity during mating. 相似文献
195.
The measurement of acyl-CoA dehydrogenase activities is an essential part of the investigation of patients with suspected defects in fatty acid oxidation. Multiple methods are available for the synthesis of the substrates used for measuring acyl-CoA dehydrogenase activities; however, the yields are low and the products are used without purification. In addition, the reported characterization of acyl-CoAs focuses on the CoA moiety, not on the acyl group. Here we describe the synthesis of three medium-chain acyl-CoAs from mixed anhydrides of the fatty acids using an aqueous-organic solvent mixture optimized to obtain the highest yield. First, cis-4-decenoic acid and 2,6-dimethylheptanoic acid were prepared (3-phenylpropionic acid is commercially available). These were characterized by gas chromatography/mass spectrometry (GC/MS), 1H nuclear magnetic resonance (NMR), and 13C NMR. Then cis-4-decenoyl-CoA, 3-phenylpropionyl-CoA, and 2,6-dimethylheptanoyl-CoA were synthesized. These were then purified by ion exchange solid-phase extraction using 2-(2-pyridyl)ethyl-functionalized silica gel, followed by reversed-phase semipreparative high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The purified acyl-CoAs were characterized by analytical HPLC-UV followed by data-dependent tandem mass spectrometry (MS/MS) analysis on the largest responding MS mass (HPLC-UV-MS-MS/MS) and 13C NMR. The yields of the purified acyl-CoAs were between 75% and 78% based on coenzyme A trilithium salt (CoASH). Acyl-CoA dehydrogenase activities were measured in rat skeletal muscle mitochondria using, as substrates, the synthesized cis-4-decenoyl-CoA, 3-phenylpropionyl-CoA, and 2,6-dimethylheptanoyl-CoA. These results were compared with the results using our standard substrates butyryl-CoA, octanoyl-CoA, and palmitoyl-CoA. 相似文献
196.
El-Shemy HA Khalafalla MM Fujita K Ishimoto M 《Journal of biochemistry and molecular biology》2006,39(1):61-67
Molecular co-suppression phenomena are important to consider in transgene experiments. Embryogenic cells were obtained from immature cotyledons and engineered with two different gene constructs (pHV and pHVS) through particle bombardment. Both constructs contain a gene conferring resistance to hygromycin (hpt) as a selective marker and a modified glycinin (11S globulin) gene (V3-1) as a target. sGFP(S65T) as a reporter gene was, however, inserted into the flanking region of the V3-1 gene (pHVS). Fluorescence microscopic screening after the selection of hygromycin, identified clearly the expression of sGFP(S65T) in the transformed soybean embryos bombarded with the pHVS construct. Stable integration of the transgenes was confirmed by polymerase chain reaction (PCR) and Southern blot analysis. Seeds of transgenic plants obtained from the pHV construct frequently lacked an accumulation of endogenous glycinin, which is encoded by homologous genes to the target gene V3-1. Most of the transgenic plants expressing sGFP(S65T) showed highly accumulation of glycinin. The expression of sGFP(S65T) and V3-1 inherits into the next generations. sGFP(S65T) as a reporter gene may be useful to increase the transformation efficiency of transgenic soybean with avoiding gene co-suppression. 相似文献
197.
El-Bestawy E Hussein H Baghdadi HH El-Saka MF 《Journal of industrial microbiology & biotechnology》2005,32(5):195-203
The present work compared chemical and biological treatment methods to achieve the most efficient treatment for the reduction or elimination of phosphorus and nitrogen from mixed industrial–domestic wastewaters. Batch chemical precipitation by ferric chloride and aluminum sulfate (alum) and a continuous biological suspended growth system were investigated as well as the optimum operating conditions. Concerning chemical treatment, Alum generally achieved a higher removal efficiency percentage for the investigated pollutants compared with FeCl3 at their optimum pH and dose, especially with chemical oxygen demand (COD). FeCl3 treatment achieved success only with phosphorus removal, while none of the COD, 5-day biochemical oxygen demand (BOD5), total nitrogen (TN) and N–NH3 achieved acceptable treatment and remained above the maximum permissible limits (MPL). Thus, for such wastewaters, alum is more efficient than FeCl3. Biological treatment exhibited higher efficiencies, particularly towards nitrogen. TN removal increased by increasing the flow rate to 30–60 l/day. N–NH3 removal was effective at the slowest flow rate and decreased with increasing flow rate, while an opposite trend was recorded for N–NO3. At all flow rates, phosphorus levels were below the accepted MPL for discharging into natural systems. Moreover, there was a general trend for the proposed biological treatment to achieve a high removal efficiency for BOD5 and COD, bringing them to acceptable levels to be released into watercourses safely, especially at the slowest flow rates. Thus, integration between the proposed chemical and biological treatment is highly recommended, producing high-quality effluents acceptable by the environmental law. 相似文献
198.
Surfactant protein D binds selectively to Klebsiella pneumoniae lipopolysaccharides containing mannose-rich O-antigens 总被引:2,自引:0,他引:2
Sahly H Ofek I Podschun R Brade H He Y Ullmann U Crouch E 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(6):3267-3274
Surfactant protein D (SP-D) plays important roles in the regulation of innate immune responses in the lung. We have previously shown that SP-D can agglutinate and enhance the macrophage-dependent killing of specific unencapsulated phase variants of Klebsiella pneumoniae. In the present studies, we used 16 clinical isolates of Klebsiella representing four O-serotypes and examined the interaction of SP-D with their isolated LPSs. Although SP-D bound to the core oligosaccharide of rough LPS from all isolates, it selectively bound to smooth forms of LPS expressed by O-serotypes with mannose-rich repeating units in their O-polysaccharides. SP-D was more potent in agglutinating unencapsulated phase variants of O-serotypes expressing these SP-D "reactive" O-polysaccharides, and more effectively inhibited the adhesion of these serotypes to lung epithelial cells. This novel anti-adhesion activity required the multimerization of trimeric SP-D subunits (dodecamers). Klebsiella serotypes expressing "nonreactive" LPS O-Ags were isolated at a significantly higher frequency from patients with K. pneumoniae. Our findings suggest that SP-D plays important roles in the clearance of opportunistic Gram-negative bacteria and contributes to known serotypic differences in the pathogenicity of Klebsiella through specific interactions with O-polysaccharides. 相似文献
199.