Key residues revealed in a major conformational epitope of the U1-70K protein

Epitopes depending on three-dimensional folding of proteins have during recent years been acknowledged to be main targets for many autoantibodies. However, a detailed resolution of conformation-dependent epitopes has to date not been achieved in spite of its importance for understanding the complex interaction between an autoantigen and the immune system. In analysis of immunodominant epitopes of the U1-70K protein, the major autoantigen recognized by human ribonucleoprotein (RNP)-positive sera, we have used diversely mutated recombinant Drosophila melanogaster 70K proteins as antigens in assays for human anti-RNP antibodies. Thus, the contribution of individual amino acids to antigenicity could be assayed with the overall structure of the major antigenic domain preserved, and analysis of how antigenicity can be reconstituted rather than obliterated was enabled. Our results reveal that amino acid residue 125 is situated at a crucial position for recognition by human anti-RNP autoantibodies and that flanking residues at positions 119–126 also appear to be of utmost importance for recognition. These results are discussed in relation to structural models of RNA-binding domains, and tertiary structure modeling indicates that the residues 119–126 are situated at easily accessible positions in the end of an α-helix in the RNA binding region. This study identifies a major conformation-dependent epitope of the U1-70K protein and demonstrates the significance of individual amino acids in conformational epitopes. Using this model, we believe it will be possible to analyze other immunodominant regions in which protein conformation has a strong impact.

Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2

Level of physical activity is linked to improved glucose homeostasis. We determined whether exercise alters the expression and/or activity of proteins involved in insulin-signal transduction in skeletal muscle. Wistar rats swam 6 h per day for 1 or 5 days. Epitrochlearis muscles were excised 16 h after the last exercise bout, and were incubated with or without insulin (120 nM). Insulin-stimulated glucose transport increased 30% and 50% after 1 and 5 days of exercise, respectively. Glycogen content increased 2- and 4-fold after 1 and 5 days of exercise, with no change in glycogen synthase expression. Protein expression of the glucose transporter GLUT4 and the insulin receptor increased 2-fold after 1 day, with no further change after 5 days of exercise. Insulin-stimulated receptor tyrosine phosphorylation increased 2-fold after 5 days of exercise. Insulin-stimulated tyrosine phosphorylation of insulin-receptor substrate (IRS) 1 and associated phosphatidylinositol (PI) 3-kinase activity increased 2.5- and 3.5-fold after 1 and 5 days of exercise, despite reduced (50%) IRS-1 protein content after 5 days of exercise. After 1 day of exercise, IRS-2 protein expression increased 2.6-fold and basal and insulin-stimulated IRS-2 associated PI 3-kinase activity increased 2.8-fold and 9-fold, respectively. In contrast to IRS-1, IRS-2 expression and associated PI 3-kinase activity normalized to sedentary levels after 5 days of exercise. Insulin-stimulated Akt phosphorylation increased 5-fold after 5 days of exercise. In conclusion, increased insulin-stimulated glucose transport after exercise is not limited to increased GLUT4 expression. Exercise leads to increased expression and function of several proteins involved in insulin-signal transduction. Furthermore, the differential response of IRS-1 and IRS-2 to exercise suggests that these molecules have specialized, rather than redundant, roles in insulin signaling in skeletal muscle.

Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells

Recent evidence suggests that the Myc and Mad1 proteins are implicated in the regulation of the gene encoding the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. We have analyzed the in vivo interaction between endogenous c-Myc and Mad1 proteins and the hTERT promoter in HL60 cells with the use of the chromatin immunoprecipitation assay. The E-boxes at the hTERT proximal promoter were occupied in vivo by c-Myc in exponentially proliferating HL60 cells but not in cells induced to differentiate by DMSO. In contrast, Mad1 protein was induced and bound to the hTERT promoter in differentiated HL60 cells. Concomitantly, the acetylation of the histones at the promoter was significantly reduced. These data suggest that the reciprocal E-box occupancy by c-Myc and Mad1 is responsible for activation and repression of the hTERT gene in proliferating and differentiated HL60 cells, respectively. Furthermore, the histone deacetylase inhibitor trichostatin A inhibited deacetylation of histones at the hTERT promoter and attenuated the repression of hTERT transcription during HL60 cell differentiation. In addition, trichostatin A treatment activated hTERT transcription in resting human lymphocytes and fibroblasts. Taken together, these results indicate that acetylation/deacetylation of histones is operative in the regulation of hTERT expression.

Horizontal transfer of oncogenes by uptake of apoptotic bodies

Tumor formation involves the accumulation of a series of genetic alterations that are required for malignant growth. In most malignancies, genetic changes can be observed at the chromosomal level as losses or gains of whole or large portions of chromosomes. Here we provide evidence that tumor DNA may be horizontally transferred by the uptake of apoptotic bodies. Phagocytosis of apoptotic bodies derived from H-rasV12- and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumorigenic phenotype in vivo. Fluorescence in situ hybridization analysis revealed the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propagated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These results suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary for tumor formation.

El acceso abierto en ciencias sociales: notas sociológicas sobre publicaciones, comunidades y campos

En el presente artículo proponemos evitar las caracterizaciones abstractas y políticas del Open Access para pasar a evaluar empíricamente su funcionamiento. Solo apartándonos de los manifiestos programáticos y los listados de beneficios teóricos de dichas prácticas podremos valorar en su justa medida las resistencias existentes y aprovechar sus potencialidades reales. En concreto, se propone estudiar el Open Access en las Ciencias Sociales (en comparación con las Ciencias Naturales) y entender que todavía estamos ante un proceso desigual de difusión del conocimiento académico debido, en parte, a dos nociones sociológicas centrales (de dos autores también centrales en las propias Ciencias Sociales): i) la arquitectura diferencial de sus “comunidades científicas” (Merton) y ii) las diferentes reglas de “campo académico” (Bourdieu) configuradas a partir del dominio de los índices de impacto en las ciencias contemporáneas.

London, England, 1847 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: London and its environs : containing the boundaries of the metropolitan boroughs, the different railroads & stations, the new cemeteries, roads, docks, canals, and all the modern improvements : this map is chiefly from the Ordinance Survey, the railroads and other improvements are from the official copies, the boroughs of Marylebone from the survey published by M.r Britton, the whole corrected from personal observation & measurement, drawn and engraved by B. R. Davies. It was published by C. F. Cheffins, lithog : Wm. S. Orr & Co., Dec. 1, 1847. Scale [ca. 1:42,000]. Covers a portion of Greater London. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected buildings, built-up areas, cemeteries, parks, Borough boundaries, and more. Relief is shown by hachures. Includes legend below lower margin. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

London, England : parishes, districts, and extra parochial places, 1884 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of London and its environs : shewing the boundary of the jurisdiction of the metropolitan board of work, also the boundaries of the city of London, the Parishes, the Districts & Extra Parochial Places. It was published by Edward Standford, April 21, 1884. Scale [ca. 1:31,680]. This map is part of a 5 map set showing various thematic districts and boundaries of the London region. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected private and public buildings, towns and villages, cemeteries, parks, farms, parish, district, and extra parochial place boundaries, and more. Relief is shown by hachures. Includes notes and indices. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

London, England : water companies' districts, 1884 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of London and its environs : shewing the boundary of the jurisdiction of the metropolitan board of work, also the boundaries of the city of London, and of the water companies' disticts. It was published by Edward Standford, April 21, 1884. Scale [ca. 1:31,680]. This map is part of a 5 map set showing various thematic districts and boundaries of the London region. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected private and public buildings, towns and villages, cemeteries, parks, farms, water district boundaries, and more. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

London, England : gas companies' districts, 1884 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of London and its environs : shewing the boundary of the jurisdiction of the metropolitan board of work, also the boundaries of the city of London, and the gas companies' districts. It was published by Edward Standford, April 21, 1884. Scale [ca. 1:31,680]. This map is part of a 5 map set showing various thematic districts and boundaries of the London region. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected private and public buildings, towns and villages, cemeteries, parks, farms, gas companies' districts, and more. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

London, England : Poor Law unions, 1884 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of London and its environs : shewing the boundary of the jurisdiction of the metropolitan board of work, also the boundaries of the city of London, and of the Poor Law unions. It was published by Edward Standford, April 21, 1884. Scale [ca. 1:31,680]. This map is part of a 5 map set showing various thematic districts and boundaries of the London region. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected private and public buildings, towns and villages, cemeteries, parks, farms, Poor Law unions, and more. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

London, England : Parliamentary boroughs, 1884 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of London and its environs : shewing the boundary of the jurisdiction of the metropolitan board of work, also the boundaries of the city of London, and of the Parliamentary boroughs. It was published by Edward Standford, April 21, 1884. Scale [ca. 1:31,680]. This map is part of a 5 map set showing various thematic districts and boundaries of the London region. The image inside the map neatline is georeferenced to the surface of the earth and fit to the British National Grid coordinate system (British National Grid, Airy Spheroid OSGB (1936) Datum). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected private and public buildings, towns and villages, cemeteries, parks, farms, Parliamentary boroughs, and more. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Rose clover, a new winter legume /

Mode of access: Internet.

Improving Klamath weed ranges /

Mode of access: Internet.

Oceanic conditions off Northeastern Brazil, February-March and October-November 1966

"CG 373-34."

WEBSEC-70 : an ecological survey in the eastern Chukchi Sea, September-October 1970 /

"CG 373-50."