Sec61p Serves Multiple Roles in Secretory Precursor Binding and Translocation into the Endoplasmic Reticulum Membrane

The evolutionarily conserved Sec61 protein complex mediates the translocation of secretory proteins into the endoplasmic reticulum. To investigate the role of Sec61p, which is the main subunit of this complex, we generated recessive, cold-sensitive alleles of sec61 that encode stably expressed proteins with strong defects in translocation. The stage at which posttranslational translocation was blocked was probed by chemical crosslinking of radiolabeled secretory precursors added to membranes isolated from wild-type and mutant strains. Two classes of sec61 mutants were distinguished. The first class of mutants was defective in preprotein docking onto a receptor site of the translocon that included Sec61p itself. The second class of mutants allowed docking of precursors onto the translocon but was defective in the ATP-dependent release of precursors from this site that in wild-type membranes leads to pore insertion and full translocation. Only mutants of the second class were partially suppressed by overexpression of SEC63, which encodes a subunit of the Sec61 holoenzyme complex responsible for positioning Kar2p (yeast BiP) at the translocation channel. These mutants thus define two early stages of translocation that require SEC61 function before precursor protein transfer across the endoplasmic reticulum membrane.

Y box-binding protein-1 binds preferentially to single-stranded nucleic acids and exhibits 3′→5′ exonuclease activity

We have previously shown that Y box-binding protein-1 (YB-1) binds preferentially to cisplatin-modified Y box sequences. Based on structural and biochemical data, we predicted that this protein binds single-stranded nucleic acids. In the present study we confirmed the prediction and also discovered some unexpected functional features of YB-1. We found that the cold shock domain of the protein is necessary but not sufficient for double-stranded DNA binding while the C-tail domain interacts with both single-stranded DNA and RNA independently of the cold shock domain. In an in vitro translation system the C-tail domain of the protein inhibited translation but the cold shock domain did not. Both in vitro pull-down and in vivo co-immunoprecipitation assays revealed that YB-1 can form a homodimer. Deletion analysis mapped the C-tail domain of the protein as the region of homodimerization. We also characterized an intrinsic 3′→5′ DNA exonuclease activity of the protein. The region between residues 51 and 205 of its 324-amino acid extent is required for full exonuclease activity. Our findings suggest that YB-1 functions in regulating DNA/RNA transactions and that these actions involve different domains.

Submillisecond events in protein folding.

The pathway of protein folding is now being analyzed at the resolution of individual residues by kinetic measurements on suitably engineered mutants. The kinetic methods generally employed for studying folding are typically limited to the time range of > or = 1 ms because the folding of denatured proteins is usually initiated by mixing them with buffers that favor folding, and the dead time of rapid mixing experiments is about a millisecond. We now show that the study of protein folding may be extended to the microsecond time region by using temperature-jump measurements on the cold-unfolded state of a suitable protein. We are able to detect early events in the folding of mutants of barstar, the polypeptide inhibitor of barnase. A preliminary characterization of the fast phase from spectroscopic and phi-value analysis indicates that it is a transition between two relatively solvent-exposed states with little consolidation of structure.

Tributirina apresenta atividade quimiopreventiva quando administrada isoladamente, mas não em associação com a vitamina A, em ratos submetidos a modelo de carcinogênese de cólon

Avaliou-se a atividade quimiopreventiva da tributirina (TB), e da vitamina A (VA) administradas em associação ou não, antes, durante e após a iniciação em ratos submetidos a modelo de carcinogênese de cólon. Ratos Wistar receberam VA [1 mg/100 g de p.c (grupo VA)], tributirina [200 mg/100 g de p.c (grupo TB)] ou associação de VA com TB (grupo VA+TB). Ratos tratados com óleo de milho e maltodextrina serviram como controle (GC). Avaliou-se a presença de focos de criptas aberrantes (FCA) e sua localização nos cólons, além de danos e do padrão de metilação global do DNA na mucosa colônica. No cólon total, distal e proximal, o grupo TB apresentou menor (p<0,05) número de FCA com 4 ou mais criptas/cm2, considerados mais agressivos, em relação ao GC. Quanto aos danos no DNA, os grupos VA, TB e VA+TB apresentaram cometas de comprimentos menores (p<0,05) em comparação ao GC. Não houve diferenças estatisticamente significantes quanto ao padrão de metilação global do DNA. Assim, TB consiste em agente quimiopreventivo promissor da carcinogênese de cólon quando administrada isoladamente, mas não em associação com a VA. 15

Annotated almanac, 1775

Almanac containing one laid-in leaf and interleaved pages with entries in John Winthrop's hand. The interleaved pages include entries include brief, nearly daily notes of social engagements and travel by Winthrop during the year the Winthrops were forced to evacuate Cambridge because of the Revolutionary War. The short entries include notes of the Battle of Concord (April 19), a fire in Boston (May 17), the Battle of Bunker Hill (June 17), the choosing of councillors at Concord (June 21), and the notable entries "wth Genl Washington (August 12)" and "All day packg up Apparatus & Library" (June 16). The laid-in leaf contains an account of household purchases made while the Winthrops were living with Nehemiah Abbot Andover from May to June and later in Concord. The laid-in leaf is written on a note beginning "Mr. Winthrop presents his most respectful compliments to the Hon'ble Col. Hancock and to the rest of the Gentlemen Select-men..."

Letters from Condy Raguet,

Four letters containing news of Royalist Army officers, including Vice Roy José de la Serna, arriving in Rio de Janeiro after their defeat at the Battle of Ayacucho. Raguet also writes of the public reaction to Bolívar’s victory.

Japan, ca. 1861 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Empire of Japan, engraved by J. & C. Walker. It was published under the Superintendence of the Society for the Diffusion of Useful knowledge, [by] Edward Stanford, ca. 1861. Scale [ca. 1:4,400,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic coordinate system. 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 drainage, cities and other human settlements, roads, volcanos, shoreline features, harbors, and more. Relief shown by hachures. Includes notes and insets of Nagasaki harbor, and of Yeso.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Fort Sanders, Knoxville, Tennessee,and vicinity, 1863 (Raster Image)

This layer is a georeferenced raster image of the untitled historic paper manuscript map: [Map of Fort Sanders, Knoxville, Tennessee, and vicinity showing troop lines]. It was sketched ca.1863. Scale not given. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Tennessee State Plane Coordinate System (in Meters) (Fipszone 4100). 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, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, troop location, fortifications, batteries, selected points of military interest, and more. Relief shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps of the Civil War from the Harvard Map Collection. Many items from this selection are from a collection of maps deposited by the Military Order of the Loyal Legion of the United States Commandery of the State of Massachusetts (MOLLUS) in the Harvard Map Collection in 1938. These maps typically portray both natural and manmade features, in particular showing places of military importance. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Quebec, Canada, 1759 (Raster Image)

This layer is a georeferenced raster image of the historic paper manuscript map entitled: Plan of the town and basin of Quebec : and part of the adjacent country shewing the principal encampments and works of the British army commanded by Major Genl. Wolfe and those of the French army by Lieut. Genl. the Marquis of Montcalm during the attack in 1759. Scale [ca. 1:9,600]. This image consists of images of a two sheet source map that have been stitched together using image editing software to create one image. Manuscript copy of a map. Copied by [Whlkington?] in 1857. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Universal Transverse Mercator (UTM) Zone 19N NAD 1983 coordinate system. 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, drainage, selected buildings, fortification, ship and troop movements, and places of military interest for the Battle of Quebec, 1759, and more. Relief is shown by hachures. Includes index and text. 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.

Cape Town , South Africa, 1942 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Capetown Harbor, Union of South Africa, drawn in Geography Division, O.S.S. Provisional ed. It was published by the OSS in 1942. Scale [ca. 1:23,000]. Covers the Table Bay harbor area of Cape Town, South Africa. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'WGS 1984 UTM 34S' coordinate system. 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 and industries, proposed and existing wharves and docks, and more. Shows plans for the proposed reclamation area of the harbor. 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.

Sharḥ al-ṣadr bi-Ghazwat Badr

li-ʻAbd Allāh al-Shabrāwī.

Nieuwe en Accurate Caart vann de Omleggende Lande van Belgrado: als mede des selfs Belegeringh, ende Marse der Keyserlycke Armee, Ao. 1717

by Joachim Ottens.

Dialogue with the Eurasian Union on Ukraine – an opportunity or a trap? OSW COMMENTARY No. 154, 2014-12-01

The Eurasian Union (or, to give it its full name, the Eurasian Economic Union, EEU) is Russia's flagship project, by use of which it aims to institutionally subordinate the post-Soviet states to itself using political ties and the projected common economic space. The Kremlin has so far managed to persuade Belarus and Kazakhstan, and tentatively also Armenia, to join this integration project, which on the surface looks like a multilateral initiative but in reality conceals a network of bilateral relations centred on Russia. However, in order for Russia to reconstruct its influence in its neighbourhood permanently and without change, it is of key importance that Ukraine is incorporated into the EEU. That still seemed feasible even in 2013, but the Maidan and the Russian-Ukrainian war have undone this possibility. However, they also opened up an alternative scenario for Russia, one in which the Western states recognise the Eurasian Union as a legitimate partner in discussions about a new order in Europe with a view to restoring peace in Ukraine. It is worth taking into account the strategic consequences of that scenario. We need to consider if the idea which Moscow has been lobbying for – and which has found some supporters in Brussels and Berlin – threatens to take us back to the Cold War system of geopolitical blocs and implies recognition of Russia's dominance over Ukraine and the other Eastern Partnership countries?

Surgical cryoablation for ventricular tachyarrhythmia arising from the left ventricular outflow tract region.

BACKGROUND Ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) region can be inaccessible for ablation because of epicardial fat or overlying coronary arteries. OBJECTIVE We describe surgical cryoablation of this type of VA. METHODS From March 2009 to 2014, 190 consecutive patients with VAs originating from the LVOT underwent ablation at our institution. Four patients (2%) underwent surgical cryoablation for highly symptomatic VAs after failing catheter ablation. RESULTS In all patients, endocardial or percutaneous epicardial mapping was consistent with origin in the LVOT. In 2 patients, the points of earliest activation during VAs were marked with a bipolar pacing lead in the overlying cardiac vein for guidance during surgery. Surgical cryoablation was successful in 3 of the 4 patients. The fourth patient subsequently had successful endocardial catheter ablation. During a mean follow-up of 22 ± 16 months (range 4-42 months), all patients showed abolition of or marked reduction in symptomatic VA. However, 1 patient subsequently required percutaneous intervention to the left anterior descending coronary artery; another developed progressive left ventricular systolic dysfunction caused by nonischemic cardiomyopathy; and a third patient underwent permanent pacemaker implantation because of complete atrioventricular block after concomitant aortic valve replacement. CONCLUSION Surgical cryoablation is an option for highly symptomatic drug-resistant VAs emanating from the LVOT region. Despite extensive preoperative mapping, the procedure is not effective for all patients, and coronary injury is a risk.

Entre la historia y el mito : La figura de Ramsés II ante los enemigos en relieves y textos de la Batalla de Kadesh

De acuerdo a lo que se ha dado en llamar "historia del sentido" (Assmann, 2005), cada sociedad posee una forma cultural que le es inherente y es precisamente en ella donde adquieren sentido los acontecimientos y procesos históricos, comprensibles sólo a través de los discursos producidos. Los relieves y las inscripciones de la Batalla de Kadesh, durante el reinado de Ramsés II (1279-1213 a.C.) constituyen un claro ejemplo de rememoración y manifestación de esos discursos. En este trabajo, nos proponemos analizarlos como ejemplos de procesos constructivos de la "memoria cultural" (Assmann, 2008), tomando como categorías de análisis los postulados de la semiótica de Umberto Eco (1994 (1973); 2013 (1968)) y del análisis de la imagen de Martine Joly (2012 (1993)). Como premisa básica, consideraremos a los relieves y las inscripciones que los acompañaban como una unidad total narrativa, como discursos que se completan y complementan, para ser eficaces.