42 research outputs found

    Cataract surgery at Aravind Eye Hospitals: 1988–2008

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    In the 1980s, cataract was the major cause of blindness in India and was responsible for 80% of all blindness. This prompted the Indian government to launch a national cataract control programme, which succeeded in lowering the prevalence of blindness from 1.49% to 1.1%. In addition, by 2000, this programme had reduced the proportion of people blind due to cataract from 80% to 62%.Aravind Eye Hospitals contributed to a third of all cataract operations in the state of Tamil Nadu during the last two decades and played a major part in lowering the rate of blindness in that state. By 2000, the prevalence level of blindness was just 0.78%, compared to the national level of 1.11%

    Carotid artery insufficiency

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    Albers - schonberg disease (osteopetrosis)

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    Unilateral proptosis due to fibrous dysplasia

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    Visualizing the Role of 2’-OH rRNA Methylations in the Human Ribosome Structure

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    Chemical modifications of RNA have recently gained new attention in biological sciences. They occur notably on messenger RNA (mRNA) and ribosomal RNA (rRNA) and are important for various cellular functions, but their molecular mechanism of action is yet to be understood in detail. Ribosomes are large ribonucleoprotein assemblies, which synthesize proteins in all organisms. Human ribosomes, for example, carry more than 200 modified nucleotides, which are introduced during biogenesis. Chemically modified nucleotides may appear to be only scarcely different from canonical nucleotides, but modifications such as methylations can in fact modulate their chemical and topological properties in the RNA and alter or modulate the overall translation efficiency of the ribosomes resulting in dysfunction of the translation machinery. Recent functional analysis and high-resolution ribosome structures have revealed a large repertoire of modification sites comprising different modification types. In this review, we focus on 2′-O-methylations (2′-O-Me) and discuss the structural insights gained through our recent cryo electron microscopy (cryo-EM) high-resolution structural analysis of the human ribosome, such as their locations and their influence on the secondary and tertiary structures of human rRNAs. The detailed analysis presented here reveals that ribose conformations of the rRNA backbone differ when the 2′-OH hydroxyl position is methylated, with 3′-endo conformations being the default and the 2′-endo conformations being characteristic in that the associated base is flipped-out. We compare currently known 2′-O-Me sites in human rRNAs evaluated using RiboMethSeq and cryo-EM structural analysis and discuss their involvement in several human diseases

    Visualization of chemical modifications in the human 80S ribosome structure

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    Video showing the 3D structure of the human ribosome revealing chemical modifications of the ribosomal RNA.<br><div><br></div><div>File is provided in .mp4 format, compatible with most standard video playing software.</div><div><br></div><div>This visualization, along with the related article, presents for the first time chemical modifications of rRNA in the human ribosome introduced during biogenesis and maturation, and highlights their structural and functional role within their 3D molecular environment. Visualizations include:</div><div><br></div><div>Universally conserved rRNA modification sites (Class I)</div><div>Predicted rRNA modification sites (Class II)</div><div>Unpredicted human specific rRNA modifications (Class III)</div><div><br></div><div><div>The structure of the human 80S ribosome was determined by single particle cryo electron microscopy (cryo-EM) and refined using focused refinement of the 60S ribosomal subunit and the 40S head and body parts during image processing (resolved to 2.9, 3.0 and 3.1 Ă… average resolution, respectively (see methods in linked article).</div></div><div><br></div><div>See background below and related article linked from this data record for further details.</div><div><br></div><div><b>Background:</b></div><div>Chemical modifications of the ribosomal RNA (rRNA) of the human ribosome are introduced during biogenesis and are implicated in human protein synthesis dysregulations such as cancer and other diseases but their role therein is unknown. Here we visualize over 130 individual rRNA modifications in the three dimensional structure of the human ribosome explaining their structural and functional roles. Beyond some universally conserved sites, many eukaryote/human specific modifications and new unique sites are found that form an evolutionary extended shell compared to bacterial ribosomes and which stabilize the RNA. A series of modifications are located in vicinity to 3 bound antibiotics or are associated with degenerated states in cancer such as keto alkylations at nucleotide bases reminiscent of specialized ribosomes. This high-resolution structure of the human 80S ribosome paves the way to understanding the role of rRNA modifications in human diseases and drug-design. <br></div

    Visualization of chemical modifications in the human 80S ribosome structure

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    Chemical modifications of human ribosomal RNA (rRNA) are introduced during biogenesis and have been implicated in the dysregulation of protein synthesis, as is found in cancer and other diseases. However, their role in this phenomenon is unknown. Here we visualize more than 130 individual rRNA modifications in the three-dimensional structure of the human ribosome, explaining their structural and functional roles. In addition to a small number of universally conserved sites, we identify many eukaryote- or human-specific modifications and unique sites that form an extended shell in comparison to bacterial ribosomes, and which stabilize the RNA. Several of the modifications are associated with the binding sites of three ribosome-targeting antibiotics, or are associated with degenerate states in cancer, such as keto alkylations on nucleotide bases reminiscent of specialized ribosomes. This high-resolution structure of the human 80S ribosome paves the way towards understanding the role of epigenetic rRNA modifications in human diseases and suggests new possibilities for designing selective inhibitors and therapeutic drugs
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