β1-Integrin Cytoplasmic Subdomains Involved in Dominant Negative Function

The β1-integrin cytoplasmic domain consists of a membrane proximal subdomain common to the four known isoforms (“common” region) and a distal subdomain specific for each isoform (“variable” region). To investigate in detail the role of these subdomains in integrin-dependent cellular functions, we used β1A and β1B isoforms as well as four mutants lacking the entire cytoplasmic domain (β1TR), the variable region (β1COM), or the common region (β1ΔCOM-B and β1ΔCOM-A). By expressing these constructs in Chinese hamster ovary and β1 integrin-deficient GD25 cells (Wennerberg et al., J Cell Biol 132, 227–238, 1996), we show that β1B, β1COM, β1ΔCOM-B, and β1ΔCOM-A molecules are unable to support efficient cell adhesion to matrix proteins. On exposure to Mn++ ions, however, β1B, but none of the mutants, can mediate cell adhesion, indicating specific functional properties of this isoform. Analysis of adhesive functions of transfected cells shows that β1B interferes in a dominant negative manner with β1A and β3/β5 integrins in cell spreading, focal adhesion formation, focal adhesion kinase tyrosine phosphorylation, and fibronectin matrix assembly. None of the β1 mutants tested shows this property, indicating that the dominant negative effect depends on the specific combination of common and B subdomains, rather than from the absence of the A subdomain in the β1B isoform.

The herpes simplex virus major regulatory protein ICP4 blocks apoptosis induced by the virus or by hyperthermia.

Cells infected with herpes simplex virus 1 (HSV-1) undergo productive or latent infection without exhibiting features characteristic of apoptosis. In this report, we show that HSV-1 induces apoptosis but has evolved a function that blocks apoptosis induced by infection as well as by other means. Specifically, (i) Vero cells infected with a HSV-1 mutant deleted in the regulatory gene alpha 4 (that encodes repressor and transactivating functions), but not those infected with wild-type HSV-1(F), exhibit cytoplasmic blebbing, chromatin condensation, and fragmented DNA detected as a ladder in agarose gels or by labeling free DNA ends with terminal transferase; (ii) Vero cells infected with wild-type HSV-1(F) or cells expressing the alpha 4 gene and infected with the alpha 4- virus did not exhibit apoptosis; (iii) fragmentation of cellular DNA was observed in Vero cells that were mock-infected or infected with the alpha 4- virus and maintained at 39.5 degrees C, but not in cells infected with wild-type virus and maintained at the same temperature. Wild-type strains of HSV-1 with limited extrahuman passages, such as HSV-1 (F), carry a temperature-sensitive lesion in the alpha 4 gene and at 39.5 degrees C only alpha genes are expressed. These results indicate that the product of the alpha 4 gene is able to suppress apoptosis induced by the virus as well by other means.

Functional interaction and colocalization of the herpes simplex virus 1 major regulatory protein ICP4 with EAP, a nucleolar-ribosomal protein.

The herpes simplex virus 1 infected cell protein 4 (ICP4) binds to DNA and regulates gene expression both positively and negatively. EAP (Epstein-Barr virus-encoded small nuclear RNA-associated protein) binds to small nonpolyadenylylated nuclear RNAs and is found in nucleoli and in ribosomes, where it is also known as L22. We report that EAP interacts with a domain of ICP4 that is known to bind viral DNA response elements and transcriptional factors. In a gel-shift assay, a glutathione S-transferase (GST)-EAP fusion protein disrupted the binding of ICP4 to its cognate site on DNA in a dose-dependent manner. This effect appeared to be specifically due to EAP binding to ICP4 because (i) GST alone did not alter the binding of ICP4 to DNA, (ii) GST-EAP did not bind to the probe DNA, and (iii) GST-EAP did not influence the binding of the alpha gene trans-inducing factor (alphaTIF or VP16) to its DNA cognate site. Early in infection, ICP4 was dispersed throughout the nucleoplasm, whereas EAP was localized to the nucleoli. Late in infection, EAP was translocated from nucleoli and colocalized with ICP4 in small, dense nuclear structures. The formation of dense structures and the colocalization of EAP and ICP4 did not occur if virus DNA synthesis and late gene expression were prevented by the infection of cells at the nonpermissive temperature with a mutant virus defective in DNA synthesis, or in cells infected and maintained in the presence of phosphonoacetate, which is an inhibitor of viral DNA synthesis. These results suggest that the translocation of EAP from the nucleolus to the nucleoplasm is a viral function and that EAP plays a role in the regulatory functions expressed by ICP4.

Igreja N. Sra. da Santa Cruz dos Militares

O desenho do frontispício apresenta monumentalidade pela proporção dos cinco tramos no primeiro pavimento e três no segundo encimado por um triângulo frontão com uma cruz sobre o acrotério na parte central. A horizontalidade advém das duas volutas laterais sobre o entalhamento das portas que dão acesso aos corredores. O corpo da igreja tem uma porta central ladeada por nichos e o pórtico com colunas em pedra com capitéis jônicos são de mármore. Unindo a sacada e janelas do coro há quatro nichos para os santos evangelistas. Mestre Valentim que lá trabalhou entre 1805 a 1811, esculpiu dois deles em cedro: São Mateus e São João, recolhidos atualmente no Museu Histórico e Nacional. As quatro esculturas em mármore de Carrara nos atuais nichos são do escultor acadêmico Jean-Louis Despré, vindas da Itália em 1926. Internamente a surpresa está na alvura da ornamentação, com o mínimo de policromia e mesmo douramento, permitindo que a rica talha rococó se revele aos pouco a partir da capela-mor, obra de mestre Valentim. Na entrada, o arco ornamentado que sustenta o coro é surpreendente pelas guirlandas e buquês de flores que se adensam até quase a altura dos olhos emoldurando toda a nave com relevos simbólicos cristãos e maçônicos, típicos do Iluminismo.

Il concordato preventivo in Italia: una valutazione delle riforme e del suo utilizzo

Tra il 2005 e il 2013 la disciplina italiana sulle crisi d’impresa è stata oggetto di varie riforme, che hanno cercato di rafforzare il concordato preventivo, in particolare nella sua funzione di istituto atto a favorire la continuità di aziende in crisi non irreversibile. Anche tenendo conto degli effetti della crisi economica, tali riforme hanno conseguito l’obiettivo di allargare il ricorso al concordato, in particolare a seguito dell’introduzione di quello “in bianco”, che consente di posticipare la presentazione del piano di risanamento. Le riforme hanno anche contribuito a un lieve miglioramento della continuità aziendale. Ciò nonostante, solo una quota limitata di aziende (circa il 4,5 per cento) sopravvive dopo il concordato, la cui funzione principale è rimasta quella di fornire uno strumento liquidatorio di tipo negoziale, alternativo al fallimento che vede un maggior ruolo degli organi giudiziari. Il ricorso al concordato risulta correlato, oltre che con caratteristiche strutturali dell’impresa (un maggior peso delle immobilizzazioni materiali) e delle relazioni creditizie (un minore peso dei crediti dotati di garanzie reali), anche con la durata temporale delle procedure fallimentari nel tribunale di riferimento.

The outburst decay of the low magnetic field magnetar SGR 0418+5729

We report on the long-term X-ray monitoring of the outburst decay of the low magnetic field magnetar SGR 0418+5729 using all the available X-ray data obtained with RXTE, Swift, Chandra, and XMM-Newton observations from the discovery of the source in 2009 June up to 2012 August. The timing analysis allowed us to obtain the first measurement of the period derivative of SGR 0418+5729: ˙ P = 4(1) × 10−15 s s−1, significant at a ∼3.5σ confidence level. This leads to a surface dipolar magnetic field of Bdip 6 × 1012 G. This measurement confirms SGR 0418+5729 as the lowest magnetic field magnetar. Following the flux and spectral evolution from the beginning of the outburst up to ∼1200 days, we observe a gradual cooling of the tiny hot spot responsible for the X-ray emission, from a temperature of ∼0.9 to 0.3 keV. Simultaneously, the X-ray flux decreased by about three orders of magnitude: from about 1.4 × 10−11 to 1.2 × 10−14 erg s−1 cm−2. Deep radio, millimeter, optical, and gamma-ray observations did not detect the source counterpart, implying stringent limits on its multi-band emission, as well as constraints on the presence of a fossil disk. By modeling the magneto-thermal secular evolution of SGR 0418+5729, we infer a realistic age of ∼550 kyr, and a dipolar magnetic field at birth of ∼1014 G. The outburst characteristics suggest the presence of a thin twisted bundle with a small heated spot at its base. The bundle untwisted in the first few months following the outburst, while the hot spot decreases in temperature and size. We estimate the outburst rate of low magnetic field magnetars to be about one per year per galaxy, and we briefly discuss the consequences of such a result in several other astrophysical contexts.

Genoa, Italy, 1766 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Genova : nel solo giro delle sue mura vecchie con l'esposizione delle Chiese e luoghi principali, misurata a passi geometrici da Giacomo Brusco Ingegnere auit. It was published in 1766. Scale [ca. 1:1,250]. Covers Genoa, Italy. Map in Italian.The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'European Datum 1950 UTM Zone 32N' 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, built-up areas and selected buildings, fortification, ground cover, wharves, and more. Relief shown pictorially. Includes index.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.

Genoa, Italy, 1789 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Topografia del porto e cittá di Genova : nel solo ristretto delle sue mura vecchie, coll' indicazione delle chiese, e luoghi principali, delineata da Giacomo Bruschi Cap. Ingegniere 1789 ; Guidotto, scolpi. It was published by Ivone Gravier in 1789. Scale [ca. 1:5,000]. Covers Genoa, Italy. Map in Italian.The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'European Datum 1950 UTM Zone 32N' 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, built-up areas and selected buildings, fortification, ground cover, wharves, and more. Relief shown by hachures. Includes index.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.

Albania Propria ouero Superiore detta anche Macedonia Occidentale

descritta con disegni fatti sul luogo da Giacomo Cantelli da Vignola suddito e geografo del Sereniss. Sig. Duca di Modena.

Online Personal Data Processing and EU Data Protection Reform. CEPS Task Force Report, April 2013

This report sheds light on the fundamental questions and underlying tensions between current policy objectives, compliance strategies and global trends in online personal data processing, assessing the existing and future framework in terms of effective regulation and public policy. Based on the discussions among the members of the CEPS Digital Forum and independent research carried out by the rapporteurs, policy conclusions are derived with the aim of making EU data protection policy more fit for purpose in today’s online technological context. This report constructively engages with the EU data protection framework, but does not provide a textual analysis of the EU data protection reform proposal as such.

The steel industry in the European Union: Composition and drivers of energy prices and costs. CEPS Special Report No. 80, 17 December 2013

This report assesses the energy costs borne by the steel industry in the EU between 2010 and 2012, and compares the energy costs, including both the energy components and other regulatory costs, to production costs, turnover and margins of steel-makers. The estimates of energy costs are based on primary sources, i.e. is on information provided by steel-makers through a written questionnaire. This information was validated by the research team by checking annual energy bills, when available, and other public sources. In this respect, this exercise represents a unique fact-based investigation into the costs of energy for steel-makers in Europe, whereas most of the information currently available in the public domain is based on secondary or statistical information. In 2012, the median EU steel plant pays about €33/MWh for gas, up from €26/MWh in 2010. As for electricity, in 2012 the EU median plant pays €62/MWh, up from €59/MWh in 2010. The report also includes a comparison with the prices of energy carriers paid by producers based in the US.