Identification of C1q as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1.

To examine the role of complement components as regulators of the expression of endothelial adhesive molecules in response to immune complexes (ICs), we determined whether ICs stimulate both endothelial adhesiveness for leukocytes and expression of E-selectin and intercellular and vascular cell adhesion molecules 1 (ICAM-1 and VCAM-1). We found that ICs [bovine serum albumin (BSA)-anti-BSA] stimulated endothelial cell adhesiveness for added leukocytes in the presence of complement-sufficient normal human serum (NHS) but not in the presence of heat-inactivated serum (HIS) or in tissue culture medium alone. Depletion of complement component C3 or C8 from serum did not prevent enhanced endothelial adhesiveness stimulated by ICs. In contrast, depletion of complement component C1q markedly inhibited IC-stimulated endothelial adhesiveness for leukocytes. When the heat-labile complement component C1q was added to HIS, the capacity of ICs to stimulate endothelial adhesiveness for leukocytes was completely restored. Further evidence for the possible role of C1q in mediating the effect of ICs on endothelial cells was the discovery of the presence of the 100- to 126-kDa C1q-binding protein on the surface of endothelial cells (by cytofluorography) and of message for the 33-kDa C1q receptor in resting endothelial cells (by reverse transcription-PCR). Inhibition of protein synthesis by cycloheximide blocked endothelial adhesiveness for leukocytes stimulated by either interleukin 1 or ICs in the presence of NHS. After stimulation with ICs in the presence of NHS, endothelial cells expressed increased numbers of adhesion molecules (E-selectin, ICAM-1, and VCAM-1). Endothelial expression of adhesion molecules mediated, at least in part, endothelial adhesiveness for leukocytes, since leukocyte adhesion was blocked by monoclonal antibodies directed against E-selectin. These studies show that ICs stimulate endothelial cells to express adhesive proteins for leukocytes in the presence of a heat-labile serum factor. That factor appears to be C1q.

Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage.

The activation of heat shock genes by diverse forms of environmental and physiological stress has been implicated in a number of human diseases, including ischemic damage, reperfusion injury, infection, neurodegeneration, and inflammation. The enhanced levels of heat shock proteins and molecular chaperones have broad cytoprotective effects against acute lethal exposures to stress. Here, we show that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1). Perhaps relevant to its pharmacological use, indomethacin pretreatment lowers the temperature threshold of HSF1 activation, such that a complete heat shock response can be attained at temperatures that are by themselves insufficient. The synergistic effect of indomethacin and elevated temperature is biologically relevant and results in the protection of cells against exposure to cytotoxic conditions.

Regulation of cell signaling by the cytoplasmic domains of the heat-stable enterotoxin receptor: identification of autoinhibitory and activating motifs.

Infection with enterotoxigenic Escherichia coli is a leading cause of traveler's diarrhea. Many enterotoxigenic E. coli strains produce heat-stable enterotoxin (ST), a peptide that binds to the intestinal receptor guanylyl cyclase C known as STaR. The toxin-receptor interaction elevates intracellular cGMP, which then activates apical chloride secretion, resulting in secretory diarrhea. In this report, we examine how the intracellular domains of STaR participate in the propagation and regulation of signaling. We show that STaR exists as an oligomer in both the presence and the absence of toxin. We also demonstrate that deletion of the intracellular kinase-homology domain produces a constitutively active mutant, suggesting that this domain subserves an autoinhibitory function. Finally, we constructed a point mutant within a highly conserved region of the cyclase domain that completely inactivates the catalytic activity of guanylyl cyclase. Cotransfection of this point mutant with wild-type receptor causes a dominant-negative effect on receptor activation. This suggests that interaction of receptor subunits is required for toxin-induced activation and that the cyclase domain is involved in this essential interaction. We propose that the binding of ST to STaR promotes a conformational change across the cell membrane. This removes the inhibitory effects of the kinase-homology domain and promotes an interaction between cyclase domains that leads to receptor activation. The data suggest a paradigm of signal transduction that may also be relevant to other members of the guanylyl cyclase receptor family.

Variability of the ocean heat content during the last millennium - an assessment with the ECHO-g Model

Studies addressing climate variability during the last millennium generally focus on variables with a direct influence on climate variability, like the fast thermal response to varying radiative forcing, or the large-scale changes in atmospheric dynamics (e. g. North Atlantic Oscillation). The ocean responds to these variations by slowly integrating in depth the upper heat flux changes, thus producing a delayed influence on ocean heat content (OHC) that can later impact low frequency SST (sea surface temperature) variability through reemergence processes. In this study, both the externally and internally driven variations of the OHC during the last millennium are investigated using a set of fully coupled simulations with the ECHO-G (coupled climate model ECHAMA4 and ocean model HOPE-G) atmosphere-ocean general circulation model (AOGCM). When compared to observations for the last 55 yr, the model tends to overestimate the global trends and underestimate the decadal OHC variability. Extending the analysis back to the last one thousand years, the main impact of the radiative forcing is an OHC increase at high latitudes, explained to some extent by a reduction in cloud cover and the subsequent increase of short-wave radiation at the surface. This OHC response is dominated by the effect of volcanism in the preindustrial era, and by the fast increase of GHGs during the last 150 yr. Likewise, salient impacts from internal climate variability are observed at regional scales. For instance, upper temperature in the equatorial Pacific is controlled by ENSO (El Nino Southern Oscillation) variability from interannual to multidecadal timescales. Also, both the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO) modulate intermittently the interdecadal OHC variability in the North Pacific and Mid Atlantic, respectively. The NAO, through its influence on North Atlantic surface heat fluxes and convection, also plays an important role on the OHC at multiple timescales, leading first to a cooling in the Labrador and Irminger seas, and later on to a North Atlantic warming, associated with a delayed impact on the AMO.

Impacts on particles and ozone by transport processes recorded at urban and high-altitude monitoring stations

In order to evaluate the influence of particle transport episodes on particle number concentration temporal trends at both urban and high-altitude (Aitana peak-1558 m a.s.l.) stations, a simultaneous sampling campaign from October 2011 to September 2012 was performed. The monitoring stations are located in southeastern Spain, close to the Mediterranean coast. The annual average value of particle concentration obtained in the larger accumulation mode (size range 0.25–1 μm) at the mountain site, 55.0 ± 3.0 cm− 3, was practically half that of the value obtained at the urban station (112.0 ± 4.0 cm− 3). The largest difference between both stations was recorded during December 2011 and January 2012, when particles at the mountain station registered the lowest values. It was observed that during urban stagnant episodes, particle transport from urban sites to the mountain station could take place under specific atmospheric conditions. During these transports, the major particle transfer is produced in the 0.5–2 μm size range. The minimum difference between stations was recorded in summer, particularly in July 2012, which is most likely due to several particle transport events that affected only the mountain station. The particle concentration in the coarse mode was very similar at both monitoring sites, with the biggest difference being recorded during the summer months, 0.4 ± 0.1 cm− 3 at the urban site and 0.9 ± 0.1 cm− 3 at the Aitana peak in August 2012. Saharan dust outbreaks were the main factor responsible for these values during summer time. The regional station was affected more by these outbreaks, recording values of > 4.0 cm− 3, than the urban site. This long-range particle transport from the Sahara desert also had an effect upon O3 levels measured at the mountain station. During periods affected by Saharan dust outbreaks, ozone levels underwent a significant decrease (3–17%) with respect to its mean value.

Effect of water vapour condensation on the radon content in subsurface air in a hypogeal inactive-volcanic environment in Galdar cave, Spain

Fluctuations of trace gas activity as a response to variations in weather and microclimate conditions were monitored over a year in a shallow volcanic cave (Painted Cave, Galdar, Canary Islands, Spain). 222Rn concentration was used due to its greater sensitivity to hygrothermal variations than CO2 concentration. Radon concentration in the cave increases as effective vapour condensation within the porous system of the rock surfaces inside the cave increases due to humidity levels of more than 70%. Condensed water content in pores was assessed and linked to a reduction in the direct passage of trace gases. Fluctuations in radon activity as a response to variations in weather and microclimate conditions were statistically identified by clustering entropy changes on the radon signal and parameterised to predict radon concentration anomalies. This raises important implications for other research fields, including the surveillance of shallow volcanic and seismic activity, preventive conservation of cultural heritage in indoor spaces, indoor air quality control and studies to improve understanding of the role of subterranean terrestrial ecosystems as reservoirs and/or temporary sources of trace gases.

Impedance spectroscopy study of the effect of environmental conditions in the microstructure development of OPC and slag cement mortars

In this work, the microstructure of mortars made with an ordinary Portland cement and slag cement has been studied. These mortars were exposed to four different constant temperature and relative humidity environments during a 180-day period. The microstructure has been studied using impedance spectroscopy, and mercury intrusion porosimetry as a contrast technique. The impedance spectroscopy parameters make it possible to analyze the evolution of the solid fraction formation for the studied mortars and their results are confirmed with those obtained using mercury intrusion porosimetry. The development of the pore network of mortars is affected by the environment. However, slag cement mortars are more influenced by temperature while the relative humidity has a greater influence on the OPC mortars. The results show that slag cement mortars hardened under non-optimal environments have a more refined microstructure than OPC mortars for the studied environmental conditions.

Majorca Island, Minorca Island, and Isla de Ibiza, Spain, ca. 1756 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Carte des l'isles de Maiorque, Minorque et d'Yvice, gravée par Matthieu Seutter, Geographe de S.M. Imper. et Cathol. ; Tob. Conr. Lotter, sc. It was published by M. Seutter ca. 1756. Scale [ca. 1:560,000]. Covers Majorca Island, Minorca Island, and Isla de Ibiza, Spain. Map in French.The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 31N projected 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, road, shoreline features, and more. Relief shown by hachures and pictorially. Includes 2 insets, one showing the islands and the western part of the Mediterranean, and, "Plan du port et ville de Mahon, du Fort. St. Philippe et ses fortifications."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.

Minorca Island, Spain, 1780 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A topographical map of the Isle of Minorca, geometrically survey'd by the Royal Engineers, while it remained in the possesion of the French during the last war ; and digested by L.S. de la Rochette. It was published by William Faden in 1780. Scale [ca. 1:52,800]. Covers Minorca Island, Spain. This layer is image 1 of 2 total images of the two sheet source map, representing the western portion of the map.The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 31N projected 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, roads, villages and other human settlements, fortifications, shoreline features, ground cover, and more. Relief shown by hachures. Includes text and "Explanation of some Minorcan names."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.

Minorca Island, Spain, 1780 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A topographical map of the Isle of Minorca, geometrically survey'd by the Royal Engineers, while it remained in the possesion of the French during the last war ; and digested by L.S. de la Rochette. It was published by William Faden in 1780. Scale [ca. 1:52,800]. Covers Minorca Island, Spain. This layer is image 2 of 2 total images of the two sheet source map, representing the eastern portion of the map.The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 31N projected 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, roads, villages and other human settlements, fortifications, shoreline features, ground cover, and more. Relief shown by hachures. Includes text and "Explanation of some Minorcan names."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.

Rhode Island, 1832 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A topographical map of the state of Rhode Island and Providence plantations, surveyed trigonometrically and in detail by James Stevens, topographer and civil engineer, Newport, R.I. 1831. It was published by James Stevens in 1832. Scale [ca. 1: 95,040]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Rhode Island NAD 1983 coordinate system (in Feet) (Fipszone 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, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, hotels, banks, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town and county boundaries, canals, and more. Relief shown by hachures. Depths shown by soundings. Includes Census statistics and "Remarks".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.

Hong Kong Island, 1888 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Hong Kong with British Kowloon. It was published by Stanford's Geographical Estabt. in 1888. Scale [ca. 1:21,453]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Hong Kong 1980 Grid 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, tramways, selected buildings, coffee gardens, cemeteries, shoreline features, wharves, lighthouses, and more. Relief shown by hachures and spot heights. Includes index and manuscript annotations.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.

Providence County, Rhode Island, 1851 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Providence County, Rhode Island, with some of the adjacent towns, from original surveys by H. F. Walling. It was published by G. C. Brown in 1851. Scale [ca. 1:43,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Rhode Island NAD 1983 coordinate system (in Feet) (Fipszone 3800) 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, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), private buildings with names of property owners, town boundaries, and more. Relief shown by hachures. Includes also inset of the city of Providence and decorative border with 18 vignettes of notable buildings in the county.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.

Providence, Rhode Island, 1857 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the city of Providence, Rhode Island, from surveys under the direction of H.F. Walling ; engraved, printed, compiled & mounted at H.F. Walling's Map Establishment, no. 90 Fulton St., New York. It was published by F.A. Baker in 1857. Scale [1:4,200]. Covers a portion of East Providence, Rhode Island.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Rhode Island NAD 1983 coordinate system (in Feet) (Fipszone 3800) 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, railroad stations, drainage, public buildings, schools, churches, cemeteries, industry locations (e.g. mills, factories, etc.), docks and wharves, private buildings with selected names of property owners, town district boundaries, and more. Relief shown by hachures. Includes also illustrations of buildings in upper and lower margins: New Custom House, Post Office and U.S. court rooms -- Brown University -- Providence Institution for Savings -- Butler Hospital for the Insane -- First Baptist Meeting House -- Grace Church -- General railroad passenger station -- Central Congregational Church -- Providence Athenaeum -- Central Baptist Church.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 Wagner, Morris Island, South Carolina,1863 (Raster Image)

This layer is a georeferenced raster image of the historic paper manuscript map: Battery Wagner, Morris Isld., Francis D. Lee, Capt. Engrs. ; Langdon Cheves, Asst. Engr. in charge of work ; drawn by F.W. Bornemann, C.S. Engr. Office. It was drawn Nov 26, 1863. Scale [1:480]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the South Carolina State Plane Coordinate System (in Meters) (Fipszone 3900). 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 Fort dimensions and structures, landscape of area surrounding Fort, drainage, and more. 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.