A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses.

To examine the in vivo role(s) of type I interferons (IFNs) and to determine the role of a component of the type I IFN receptor (IFNAR1) in mediating responses to these IFNs, we generated mice with a null mutation (-/-) in the IFNAR1 gene. Despite compelling evidence for modulation of cell proliferation and differentiation by type I IFNs, there were no gross signs of abnormal fetal development or morphological changes in adult IFNAR1-/- mice. However, abnormalities of hemopoietic cells were detected in IFNAR1 -/- mice. Elevated levels of myeloid lineage cells were detected in peripheral blood and bone marrow by staining with Mac-1 and Gr-1 antibodies. Furthermore, bone marrow macrophages from IFNAR1 -/- mice showed abnormal responses to colony-stimulating factor 1 and lipopolysaccharide. IFNAR1 -/- mice were highly susceptible to viral infection: viral titers were undetected 24 hr after infection of IFNAR1 +/+ mice but were extremely high in organs of IFNAR1 -/- mice, demonstrating that the type I IFN system is a major acute antiviral defence. In cell lines derived from IFNAR1 -/- mice, there was no signaling in response to IFN-alpha or -beta as measured by induction of 2'-5' oligoadenylate synthetase, antiviral, or antiproliferative responses. Importantly, these studies demonstrate that type I IFNs function in the development and responses of myeloid lineage cells, particularly macrophages, and that the IFNAR1 receptor component is essential for antiproliferative and antiviral responses to IFN-alpha and -beta.

STAT3 activation by cytokines utilizing gp130 and related transducers involves a secondary modification requiring an H7-sensitive kinase.

Ciliary neurotrophic factor, oncostatin M, leukemia-inhibitory factor, and interleukin 6 are related cytokines that initiate signaling by homodimerizing the signal-transducing receptor component gp130 or by heterodimerizing gp130 with a gp130-related receptor component. Receptor dimerization in turn activates receptor-associated kinases of the Jak/Tyk family, resulting in the rapid tyrosine phosphorylation of several intracellular proteins, including those of two members of the signal transducers and activators of transcription (STAT) family--STAT1 and STAT3. Here we show that all cytokines that utilize gp130 sequentially induce two distinct forms of STAT3 in all responding cells examined, with the two forms apparently differing because of a time-dependent secondary serine/threonine phosphorylation involving an H7-sensitive kinase. While both STAT3 forms bind DNA and translocate to the nucleus, the striking time-dependent progression from one form to the other implies other important functional differences between the two forms. Granulocyte colony-stimulating factor, which utilizes a receptor highly related to gp130, also induces these two forms of STAT3. In contrast to a number of other cytokines and growth factors, all cytokines using gp130 and related signal transducers consistently and preferentially induce the two forms of STAT3 as compared with STAT1; this characteristic STAT activation pattern is seen regardless of which Jak/Tyk kinases are used in a particular response, consistent with the notion that the receptor components themselves are the primary determinants of which STATs are activated.

Mitochondrial DNA replication but no nuclear DNA replication during development of Dictyostelium.

Dictyostelium discoideum cells initiate development when nutrients are depleted. DNA synthesis decreases rapidly thereafter but resumes during late aggregation, only in prespore cells. This observation has been previously interpreted as indicating progression of prespore cells through the cell cycle during development. We show that developmental DNA replication occurs only in mitochondria and not in nuclei. We also show that the prestalk morphogen known as differentiation-inducing factor 1 can inhibit mitochondrial respiration. A model is proposed for cell type divergence, based on competition to become prespores, that involves mitochondrial replication in prespore cells and reduction of mitochondrial activity in prestalk cells.

Surface signaling in pathogenesis.

Surface signaling plays a major role in fungal infection. Topographical features of the plant surface and chemicals on the surface can trigger germination of fungal spores and differentiation of the germ tubes into appressoria. Ethylene, the fruit-ripening hormone, triggers germination of conidia, branching of hyphae, and multiple appressoria formation in Colletotrichum, thus allowing fungi to time their infection to coincide with ripening of the host. Genes uniquely expressed during appressoria formation induced by topography and surface chemicals have been isolated. Disruption of some of them has been shown to decrease virulence on the hosts. Penetration of the cuticle by the fungus is assisted by fungal cutinase secreted at the penetration structure of the fungus. Disruption of cutinase gene in Fusarium solani pisi drastically decreased its virulence. Small amounts of cutinase carried by spores of virulent pathogens, upon contact with plant surface, release small amounts of cutin monomers that trigger cutinase gene expression. The promoter elements involved in this process in F. solani pisi were identified, and transcription factors that bind these elements were cloned. One of them, cutinase transcription factor 1, expressed in Escherichia coli, is phosphorylated. Several protein kinases from F. solani pisi were cloned. The kinase involved in phosphorylation of specific transcription factors and the precise role of phosphorylation in regulating cutinase gene transcription remain to be elucidated.

Tiverton, Rhode Island, 1854 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the town of Tiverton, Newport County, R.I., by Wm. G. Borden, civil engineer. It was published in 1854 by Friend & Aub. Scale [ca. 1:21,200]. Covers Tiverton, Rhode Island and a portion of Fall River, Massachusetts. "Note: this map is partly from note furnished by H.F. Walling, civil engineer, and partly from original surveys." The image inside the map neatline is georeferenced to the surface of the earth and fit to the Rhode Island State Plane Coordinate System (Feet) (FIPS 3800). 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, drainage, selected private buildings labeled with owners' names, public buildings, churches, schools, industry locations (e.g. mills, factories, mines, etc.), cemeteries, town and school district boundaries, and more. Relief shown by hachures. Includes table and view of Oliver Chace's Thread Mill. This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

Reforms in Moldova: Moderate progress and an uncertain outlook for the future. OSW Commentary No. 100, 2013-01-22

After coming to power in September 2009, the Alliance for European Integration (AIE)1 coalition began implementing a wide-ranging programme of reforms, with a view to bringing Moldova closer to the European Union, and ultimately to ensure the country’s full membership of the EU. Today, Moldova is considered a clear leader in European integration among the members of the EU’s Eastern Partnership programme. This, however, has less to do with the concrete reforms introduced by the Moldovan government, and more to do with, on the one hand, Chișinău’s excellent public relations with Brussels, achieved through effective diplomacy; and on the other hand, the growing disillusionment with the lack of progress in other Eastern Partnership countries, particularly in Ukraine. Attempts to evaluate Moldova’s reforms have proven rather problematic. On the one hand, the ruling coalition has managed to make significant progress in the areas of civil liberties, human rights and electoral reform. The government has also successfully implemented regulations which have brought Moldova closer to signing a Deep and Comprehensive Free Trade Agreement (DCFTA) with the EU, and it has made headway in talks on visa liberalisation with Brussels. On the other hand, Chișinău has still not carried out the structural and economic reforms without which real change in the country will be impossible. No reforms have been introduced in the Ministry of the Interior, the Moldovan police force, or the judiciary. The AIE has also failed to decentralise governance and has had no real success in reducing corruption; its attempts to rebuild the country’s financial institutions have proved equally unsuccessful. The main reasons for this poor performance include mutual mistrust and conflicting interests among the coalition members, a shortage of financial resources, strong resistance to change by public administration staff, and significant pressure from those political and business groups whose interests could suffer as a result of the proposed reforms. It should also be noted that since the AIE took power, the international context of the reform efforts has undergone significant changes. On the one hand, the EU has been facing an economic crisis, which has had a negative impact on Moldovan exports and contributed to the worsening of the economic situation in the country; and on the other hand, Moldova has been offered membership of the Customs Union as a viable alternative to EU membership.

Atitude dos estudantes de enfermagem ao cuidar a pessoa com dor

Introdução: Cuidar da pessoa com dor é imprescindível à excelência dos cuidados de enfermagem. Refletindo sobre a natureza desses cuidados pelos estudantes, é possível promover atitudes de abertura ao sofrimento, para que como futuros profissionais respondam à necessidade de alívio. O comportamento humano é intencional, reflete preferências e para o prever podemos simplesmente examinar atitudes. Objectivo: Estimar a validade e confiabilidade da escala e analisar a atitude dos estudantes de enfermagem ao cuidar da pessoa com dor. Material e Método: Estudo analítico, correlacional e transversal, realizado com 255 estudantes da ESSV. Os dados recolhidos através de questionário autoaplicado que integra a escala: Atitude dos Estudantes de Enfermagem ao Cuidar a Pessoa com Dor. Resultados: Após o estudo psicométrico, a escala apresenta 17 itens e 2 fatores, fator 1 “Aptidão Terapêutico-Curativa” e fator 2 “Aptidão Centrada na Pessoa”. Os estudantes apresentam uma média de idade de 21.91 anos, 77.3% do sexo feminino, maioritariamente solteiros e 40.8% frequentam o 4º ano. Todos avaliam a dor nos ensinos clínicos, 86.4% com a EN e 94.9% conjuga intervenções farmacológicas e não farmacológicas, mais de 55% emprega a diminuição do ruído e luminosidade, aplicação do frio e massagem, havendo 87.5% que usa posicionamentos. Os do sexo masculino que aplicam exercícios de relaxamento e os do sexo feminino com idade ≥21 anos, do 3º ano, apresentam uma atitude mais adequada. Conclusão: A formação no tema dor ao longo do curso é preponderante no desenvolvimento de competências, mas também na aquisição de conhecimento e promoção de atitudes. Palavras chave: Estudantes de Enfermagem, Atitude; Dor; Cuidar.

Surgical exposures and options for instrumentation in acetabular fracture fixation: Pararectus approach versus the modified Stoppa.

BACKGROUND As an alternative to the modified Stoppa approach, the Pararectus approach is used clinically for treatment of acetabular fractures involving the anterior column. The current study assessed the surgical exposure and the options for instrumentation using both of these approaches. METHODS Surgical dissections were conducted on five human cadavers (all male, mean age 88 years (82-97)) using the modified Stoppa and the Pararectus approach, with the same skin incision length (10cm). Distal boundaries of the exposed bony surfaces were marked using a chisel. After removal of all soft-tissues, distances from the boundaries in the false and true pelvis were measured with reference to the pelvic brim. The exposed bone was coloured and calibrated digital images of each inner hemipelvis were taken. The amount of exposed surface using both approaches was assessed and represented as a percentage of the total bony surface of each hemipelvis. For instrumentation, a suprapectineal quadrilateral buttress plate was used. Screw lengths were documented, and three-dimensional CT reconstructions were performed to assess screw trajectories qualitatively. Wilcoxon's signed rank test for paired groups was used (level of significance: p<0.05). RESULTS After utilization of the Pararectus approach, the distances from the farthest boundaries of exposed bone towards the pelvic brim were significantly higher in the false but not the true pelvis, compared to the modified Stoppa approach. The percentage (mean±SD) of exposed bone accessible after utilizing the Pararectus approach was 42±8%, compared to 29±6% using the modified Stoppa (p=0.011). In cadavers exposed by the Pararectus approach, screws placed for posterior fixation and as a posterior column screw were longer by factor 1.8 and 2.1, respectively (p<0.05), and screws could be placed more posteromedial towards the posterior inferior iliac spine or in line with the posterior column directed towards the ischial tuberosity. CONCLUSION Compared to the modified Stoppa, the Pararectus approach facilitates a greater surgical access in the false pelvis, provides versatility for fracture fixation in the posterior pelvic ring and allows for the option to extend the approach without a new incision.

Radiolarian-based paleotemperatures of ODP Site 177-1089 in the Atlantic Sector of the Southern Ocean

Two cores, Site 1089 (ODP Leg 177) and PS2821-1, recovered from the same location (40°56'S; 9°54'E) at the Subtropical Front (STF) in the Atlantic Sector of the Southern Ocean, provide a high-resolution climatic record, with an average temporal resolution of less than 600 yr. A multi-proxy approach was used to produce an age model for Core PS2821-1, and to correlate the two cores. Both cores document the last climatic cycle, from Marine Isotopic Stage 6 (MIS 6, ca. 160 kyr BP, ka) to present. Summer sea-surface temperatures (SSSTs) have been estimated, with a standard error of ca. +/-1.16°C, for the down core record by using Q-mode factor analysis (Imbrie and Kipp method). The paleotemperatures show a 7°C warming at Termination II (last interglacial, transition from MIS 6 to MIS 5). This transition from glacial to interglacial paleotemperatures (with maximum temperatures ca. 3°C warmer than present at the core location) occurs earlier than the corresponding shift in delta18O values for benthic foraminifera from the same core; this suggests a lead of Southern Ocean paleotemperature changes compared to the global ice-volume changes, as indicated by the benthic isotopic record. The climatic evolution of the record continues with a progressive temperature deterioration towards MIS 2. High-frequency, millennial-scale climatic instability has been documented for MIS 3 and part of MIS 4, with sudden temperature variations of almost the same magnitude as those observed at the transitions between glacial and interglacial times. These changes occur during the same time interval as the Dansgaard-Oeschger cycles recognized in the delta18Oice record of the GRIP and GISP ice cores from Greenland, and seem to be connected to rapid changes in the STF position in relation to the core location. Sudden cooling episodes ('Younger Dryas (YD)-type' and 'Antarctic Cold Reversal (ACR)-type' of events) have been recognized for both Termination I (ACR-I and YD-I events) and II (ACR-II and YD-II events), and imply that our core is located in an optimal position in order to record events triggered by phenomena occurring in both hemispheres. Spectral analysis of our SSST record displays strong analogies, particularly for high, sub-orbital frequencies, to equivalent records from Vostok (Antarctica) and from the Subtropical North Atlantic ocean. This implies that the climatic variability of widely separated areas (the Antarctic continent, the Subtropical North Atlantic, and the Subantarctic South Atlantic) can be strongly coupled and co-varying at millennial time scales (a few to 10-ka periods), and eventually induced by the same triggering mechanisms. Climatic variability has also been documented for supposedly warm and stable interglacial intervals (MIS 1 and 5), with several cold events which can be correlated to other Southern Ocean and North Atlantic sediment records.

Benthic foraminifera analysis of two sediments cores from the northern Cape Basin in the eastern South Atlantic Ocean

Two late Quaternary sediment cores from the northern Cape Basin in the eastern South Atlantic Ocean were analyzed for their benthic foraminiferal content and benthic stable carbon isotope composition. The locations of the cores were selected such that both of them presently are bathed by North Atlantic Deep Water (NADW) and past changes in deep water circulation should be recorded simultaneously at both locations. However, the areas are different in terms of primary production. One core was recovered from the nutrient-depleted Walvis Ridge area, whereas the other one is from the continental slope just below the coastal upwelling mixing area where present day organic matter fluxes are shown to be moderately high. Recent data served as the basis for the interpretation of the late Quaternary faunal fluctuations and the paleoceanographic reconstruction. During the last 450,000 years, NADW flux into the eastern South Atlantic Ocean has been restricted to interglacial periods, with the strongest dominance of a NADW-driven deep water circulation during interglacial stages 1, 9 and 11. At the continental margin, high productivity faunas and very low epibenthic d13C values indicate enhanced fluxes of organic matter during glacial periods. This can be attributed to a glacial increase and lateral extension of coastal upwelling. The long term glacial-interglacial paleoproductivity cycles are superimposed by high-frequency variations with a period of about 23,000 yr. Enhanced productivity in surface waters above the Walvis Ridge, far from the coast, is indicated during glacial stages 8, 10 and 12. During these periods, cold, nutrient-rich filaments from the mixing area were probably driven as far as to the southeastern flank of the Walvis Ridge.

Distribution of planktonic foraminifera in surface sediments of the Mediterranean Sea

The Mediterranean Sea is a partillay isolated ocean where excess evaporation over precipitation results in large east to west gradients in temperature and salinity. Recent planktonic foraminiferal distributions have been examined in 66 surface sediment samples from the Mediterranean Sea. In addition to mapping the frequency distribution of 16 species, the faunal data has been subjected to cluster analysis, factor analysis and species diversity analysis. The clustering of species yields assemblages that are clearly temperature related. A warm assemblage contains both tropical and subtropical elements, while the cool assemblage can be subdivided into cool-subtropical, transitional and polar-subpolar groupings. Factor analysis is used to delineate the geographic distribution of four faunal assemblages. Factor 1 is a tropical-subtropical assemblage dominated by Globigerinoiden ruber. It has its highest values in the warmer eastern basin. Transitional species (Globorotalia inflata and Globigerina bulloides) dominate factor 2 with highest values occurring in the cooler western basin. Factor 3 reflects the distribution of Neogloboquadrina dutertrei and is considered to be salinity dependent. Subpolar species dominate factor 4 (Neoglobuquadrina pachyderma and G. bulloides), with highest values occurring in the northern part of the western basin where cold bottom water is presently being formed. The Shannon-Weiner index of species diversity shows that high diversity exists over much of the western basin and immediately east of the Strait of Sicily. This region is marked by equitable environmental conditions and relatively even distribution of individuals among the species. Conversely, in areas where temperature and salinity values are more extreme, diversity values are lower and the assemblages are dominated by one or two species.