The reasons for higher injury detection rates when routine cystoscopy was performed are unclear. Further study is needed to identify the scenarios where routine cystoscopy is warranted after major gynecologic surgery.
Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life.DOI: http://dx.doi.org/10.7554/eLife.00324.001
Monthly intraocular injections are widely used to deliver protein-based drugs that cannot cross the blood-retina barrier for the treatment of leading blinding diseases such as age-related macular degeneration (AMD). This invasive treatment carries significant risks, including bleeding, pain, infection, and retinal detachment. Further, current therapies are associated with a rate of retinal fibrosis and geographic atrophy significantly higher than that which occurs in the described natural history of AMD. A novel therapeutic strategy which improves outcomes in a less invasive manner, reduces risk, and provides long-term inhibition of angiogenesis and fibrosis is a felt medical need. Here we show that a single intravenous injection of targeted, biodegradable nanoparticles delivering a recombinant Flt23k intraceptor plasmid homes to neovascular lesions in the retina and regresses CNV in primate and murine AMD models. Moreover, this treatment suppressed subretinal fibrosis, which is currently not addressed by clinical therapies. Murine vision, as tested by OptoMotry©, significantly improved with nearly 40% restoration of visual loss induced by CNV. We found no evidence of ocular or systemic toxicity from nanoparticle treatment. These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy.
A gram-negative bacterium which was capable of oxidizing reduced inorganic sulfur compounds was isolated from agricultural soil and designated BI-42. This new isolate grew on a wide range of organic substrates but was not able to grow autotrophically and lacked ribulose 1,s-bisphosphate carboxylase, a key enzyme of carbon dioxide fixation. These results suggested that strain BI-42 was a chemolithoheterotroph. Ammonia and nitrate were not used as sole nitrogen sources for growth, and strain BI-42 lacked glutamate synthase activity, which resulted in glutamate auxotrophy. The glutamate dehydrogenase activity of this organism was apparently insufficient for ammonia assimilation. On the basis of the results of additional biochemical tests, the G+C content of the DNA, the results of a respiratory ubiquinone analysis, the results of a 16s ribosomal DNA sequence analysis, the fatty acid composition, and the results of a membrane lipid analysis, strain BI-42 was identified as a phylogenetically and physiologically distinct taxon belonging to the alpha subclass of the Proteobucteria. Boseu thiooxiduns gen. nov., sp. nov. is the name proposed for this taxon.Sulfate is the end product of oxidations of reduced sulfur compounds by chemosynthetic, photosynthetic, and various heterotrophic microorganisms. Nature balances these oxidations through the biological reduction of sulfate to sulfide. Microorganisms utilize sulfur compounds for the biosynthesis of cellular material or transform these compounds as part of a respiratory energy-generating process. Most of the known sulfur-oxidizing bacteria belong to the genera Thiobacillus, Thiothrix, Beggiatoa, Thiomicrospira, Achromatium, DesuEfovibrio, Desulfomonas, Desulfococcus, and Desulfuromonas (18,55). Members of the genus Thiobacillus have been studied extensively to increase our understanding of the coupling of oxidation of reduced inorganic sulfur compounds to energy biosynthesis and assimilation of carbon dioxide (45). In addition, some phototrophic bacteria, such as members of the genus Chromatium, oxidize reduced inorganic sulfur compounds to provide reducing power for carbon dioxide assimilation during anaerobic photosynthesis (38).However, oxidation of sulfur compounds is not restricted to the true sulfur bacteria; this process also occurs in heterotrophic bacteria isolated from soil (54) and the marine environment (50, 51). Most of the heterotrophic bacteria that have such activities belong to the genera Pseudomonas (35), Mycobacterium, Arthrobacter, Flavobacterium (54), and Xanthobacter or are Escherichia coli strains (42). However, few of these heterotrophs have the ability to generate biologically useful energy from the oxidation of reduced sulfur compounds (31). An exception is Paracoccus denitrificans (6), which also grows autotrophically in the presence of thiosulfate. Only a few heterotrophic bacteria, such as Thiobacillus sp. strain Q (8) and Catenococcus thiocyclus (39), have been shown to obtain energy from the oxidation of sulfur compounds. This type of nutr...
This study describes microbial diversity in four tropical hot springs representing moderately thermophilic environments (temperature range: 40–58°C; pH: 7.2–7.4) with discrete geochemistry. Metagenome sequence data showed a dominance of Bacteria over Archaea; the most abundant phyla were Chloroflexi and Proteobacteria, although other phyla were also present, such as Acetothermia, Nitrospirae, Acidobacteria, Firmicutes, Deinococcus-Thermus, Bacteroidetes, Thermotogae, Euryarchaeota, Verrucomicrobia, Ignavibacteriae, Cyanobacteria, Actinobacteria, Planctomycetes, Spirochaetes, Armatimonadetes, Crenarchaeota, and Aquificae. The distribution of major genera and their statistical correlation analyses with the physicochemical parameters predicted that the temperature, aqueous concentrations of ions (such as sodium, chloride, sulfate, and bicarbonate), total hardness, dissolved solids and conductivity were the main environmental variables influencing microbial community composition and diversity. Despite the observed high taxonomic diversity, there were only little variations in the overall functional profiles of the microbial communities in the four springs. Genes involved in the metabolism of carbohydrates and carbon fixation were the most abundant functional class of genes present in these hot springs. The distribution of genes involved in carbon fixation predicted the presence of all the six known autotrophic pathways in the metagenomes. A high prevalence of genes involved in membrane transport, signal transduction, stress response, bacterial chemotaxis, and flagellar assembly were observed along with genes involved in the pathways of xenobiotic degradation and metabolism. The analysis of the metagenomic sequences affiliated to the candidate phylum Acetothermia from spring TB-3 provided new insight into the metabolism and physiology of yet-unknown members of this lineage of bacteria.
A novel bacterial strain, designated NRCPB10 T , was isolated from rhizosphere soil of chickpea (Cicer arietinum L.) in Pusa, New Delhi, India. The 16S rRNA gene sequence of strain NRCPB10 T showed highest similarity (98.9 %) to that of Rhizobium radiobacter NCPPB 2437 T , followed by Rhizobium larrymoorei AF3-10 T (97.7 %) and Rhizobium rubi IFO 13261 T (97.4 %). Phylogenetic analysis of strain NRCPB10 T based on the housekeeping genes recA and atpD confirmed its position as distinct from recognized Rhizobium species. Levels of DNA-DNA relatedness between strain NRCPB10 T and R. radiobacter ICMP 5785 T , R. larrymoorei LMG 21410 T and R. rubi ICMP 6428 T were 51.0, 32.6 and 27.3 %, respectively. Cellular fatty acids of strain NRCPB10 T were C 18 : 1 v7c (58.9 %), C 16 : 0 (15.5 %), C 19 : 0 cyclo v8c (11.5 %), iso-C 16 : 1 (5.8 %), C 16 : 0 3-OH (4.5 %), C 16 : 1 v7c (2.1 %) and C 18 : 0 (1.3 %). The G+C content of the genomic DNA of strain NRCPB10 T was 59.0 mol%. Strain NRCPB10 T did not nodulate chickpea plants or induce tumours in tobacco plants. Phenotypic and physiological properties along with SDS-PAGE of whole-cell soluble proteins differentiated strain NRCPB10 T from its closest phylogenetic neighbours. On the basis of data from the present polyphasic taxonomic study, strain NRCPB10 T is considered to represent a novel species of the genus Rhizobium, for which the name Rhizobium pusense sp. nov. is proposed. The type strain is NRCPB10 T (5LMG 25623 T 5JCM 16209 T 5NCIMB 14639 T ).
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