Convergencia de vías de señalización en un modelo de apoptosis

La sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.

Carga viral de seis tipos de Virus del Papiloma Humano de alto riesgo y su asociacion con lesiones cervicales

Introducción: La infección por un tipo de Virus del Papiloma Humano de alto riesgo (VPH-AR), es el factor principal en el desarrollo de Cáncer de Cérvix (CC). La carga viral puede modular esta asociación, por lo que resulta importante su cuantificación y el establecimiento de su relación con lesiones precursoras de CC. Metodología: 60 mujeres con lesiones escamosas intraepiteliales (LEI) y 120 mujeres sin LEI, confirmadas por colposcopia, fueron incluidas en el estudio. Se determinó la carga viral de 6 tipos de VPH-AR, mediante PCR en tiempo real. Se estimaron OR crudos y ajustados para evaluar la asociación entre la carga viral de cada tipo y las lesiones cervicales. Resultados: 93.22% de mujeres con LEI y 91.23% de mujeres negativas, fueron positivas para al menos un tipo de VPH. VPH-18 y VPH-16 fueron los tipos más prevalentes, junto con VPH-31 en mujeres sin LEI. No se encontraron diferencias estadísticamente significativas de las cargas virales entre éstos dos grupos, aunque se observó un mayor carga viral en lesiones para algunos tipos virales. Una mayor frecuencia de lesiones se asoció a infecciones con carga baja de VPH-16 (ORa: 3.53; IC95%: 1.16 – 10.74), en comparación a mujeres con carga alta de VPH-16, (ORa: 2.63; IC95%: 1.09 – 6.36). En infecciones por VPH-31, la presencia de carga viral alta, se asoció con una menor frecuencia de lesiones (ORa: 0.34; IC95%: 0.15 – 0.78). Conclusiones: La prevalencia tipo-específica de VPH se corresponde con las reportadas a nivel mundial. La asociación entre la carga viral del VPH y la frecuencia de LEI es tipo específica y podría depender de la duración de la infección, altas cargas relacionadas con infecciones transitorias, y bajas cargas con persistentes. Este trabajo contribuye al entendimiento del efecto de la carga viral en la historia natural del CC; sin embargo, estudios prospectivos son necesarios para confirmar estos resultados.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema

Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.

Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis

OBJECTIVES: To evaluate the potential improvement of antimicrobial treatment by utilizing a new multiplex polymerase chain reaction (PCR) assay that identifies sepsis-relevant microorganisms in blood. DESIGN: Prospective, observational international multicentered trial. SETTING: University hospitals in Germany (n = 2), Spain (n = 1), and the United States (n = 1), and one Italian tertiary general hospital. PATIENTS: 436 sepsis patients with 467 episodes of antimicrobial treatment. METHODS: Whole blood for PCR and blood culture (BC) analysis was sampled independently for each episode. The potential impact of reporting microorganisms by PCR on adequacy and timeliness of antimicrobial therapy was analyzed. The number of gainable days on early adequate antimicrobial treatment attributable to PCR findings was assessed. MEASUREMENTS AND MAIN RESULTS: Sepsis criteria, days on antimicrobial therapy, antimicrobial substances administered, and microorganisms identified by PCR and BC susceptibility tests. RESULTS: BC diagnosed 117 clinically relevant microorganisms; PCR identified 154. Ninety-nine episodes were BC positive (BC+); 131 episodes were PCR positive (PCR+). Overall, 127.8 days of clinically inadequate empirical antibiotic treatment in the 99 BC+ episodes were observed. Utilization of PCR-aided diagnostics calculates to a potential reduction of 106.5 clinically inadequate treatment days. The ratio of gainable early adequate treatment days to number of PCR tests done is 22.8 days/100 tests overall (confidence interval 15-31) and 36.4 days/100 tests in the intensive care and surgical ward populations (confidence interval 22-51). CONCLUSIONS: Rapid PCR identification of microorganisms may contribute to a reduction of early inadequate antibiotic treatment in sepsis.

(Table 1) Organic geochemistry of ODP Hole 134-832B and Site 134-833

Ocean Drilling Program (ODP) Leg 134 was located in the central part of the New Hebrides Island Arc, in the Southwest Pacific. Here the d'Entrecasteaux Zone of ridges, the North d'Entrecasteaux Ridge and South d'Entrecasteaux Chain, is colliding with the arc. The region has a Neogene history of subduction polarity reversal, ridge-arc collision, and back-arc spreading. The reasons for drilling in this region included the following: (1) to determine the differences in the style and time scale of deformation associated with the two ridge-like features (a fairly continuous ridge and an irregularly topographic seamount chain) that are colliding with the central New Hebrides Island Arc; (2) to document the evolution of the magmatic arc in relation to the collision process and possible Neogene reversal of subduction; and (3) to understand the process of dewatering of a small accretionary wedge associated with ridge collision and subduction. Seven sites were occupied during the leg, five (Sites 827-831) were located in the d'Entrecasteaux Zone where collision is active. Three sites (Sites 827, 828, and 829) were located where the North d'Entrecasteaux Ridge is colliding, whereas two sites (Sites 830 and 831) were located in the South d'Entrecasteaux Chain collision zone. Sites 828 (on North d'Entrecasteaux Ridge) and 831 (on Bougainville Guyot) were located on the Pacific Plate, whereas all other sites were located on a microplate of the North Fiji Basin. Two sites (Sites 832 and 831) were located in the intra-arc North Aoba Basin. Results of Leg 134 drilling showed that forearc deformation associated with the North d'Entrecasteaux Ridge and South d'Entrecasteaux Chain collision is distinct and different. The d'Entrecasteaux Zone is an Eocene subduction/obduction complex with a distinct submerged island arc. Collision and subduction of the North d'Entrecasteaux Ridge results in off scraping of ridge material and plating of the forearc with thrust sheets (flakes) as well as distinct forearc uplift. Some offscraped sedimentary rocks and surficial volcanic basement rocks of the North d'Entrecasteaux Ridge are being underplated to the New Hebrides Island forearc. In contrast, the South d'Entrecasteaux Chain is a serrated feature resulting in intermittent collision and subduction of seamounts. The collision of the Bougainville Guyot has indented the forearc and appears to be causing shortening through thrust faulting. In addition, we found that the Quaternary relative convergence rate between the New Hebrides Island Arc at the latitude of Espiritu Santo Island is as high as 14 to 16 cm/yr. The northward migration rate of the d'Entrecasteaux Zone was found the be ~2 to 4 cm/yr based on the newly determined Quaternary relative convergence rate. Using these rates we established the timing of initial d'Entrecasteaux Zone collision with the arc at ~3 Ma at the latitude of Epi Island and fixed the impact of the North d'Entrecasteaux Ridge upon Espiritu Santo Island at early Pleistocene (between 1.89 and 1.58 Ma). Dewatering is occurring in the North d'Entrecasteaux Ridge accretionary wedge, and the wedge is dryer than other previously studied accretionary wedges, such as Barbados. This could be the result of less sediment being subducted at the New Hebrides compared to the Barbados.

Paleomagnetic of basalts from ODP Site 145-883 on Detroit Seamount

Paleomagnetic data were measured from basaltic flows cored by the Ocean Drilling Program (ODP) at Site 883 on the summit of Detroit Seamount, located in the northernmost Emperor seamounts. These data are important because they reflect the paleolatitude of Hawaiian volcanism for the Late Cretaceous and bear upon geodynamic models of hotspot drift. A total of 143 samples were measured, from cores acquired at two ~20-30 m apart. Most samples gave apparently reliable magnetic directions that were analyzed in a tiered fashion to compute a composite inclination vs. depth curve. One hole gave 13 distinct inclination groups, the other 10, and the two were combined into nine groups thought to represent independent measurements of paleofield direction. These data indicate normal magnetic polarity and give a mean inclination of 61.5+10.6°/-6.4° and paleolatitude of 42.8+13.2°/-7.6° (95% confidence limits). This paleolatitude is 6.2° higher than results from another ODP site (884) drilled on the lower flank of the same seamount. The difference is thought to result partly from an age difference (1-3 Myr) and partly from incomplete averaging of paleosecular variation at both drill sites. Together, the data from the two sites reinforce the conclusion that the northern Emperor seamounts were formed far north of the present-day hotspot latitude (~19.5°N) and suggest prior estimates of the amount and rate of southward drift may have been low. This analysis also illustrates uncertainties in determining paleolatitude from a small number of lava flow units from a single drill site.

Chemical and mineral composition of rocks and sediments from the Amirante Arc

New geological and geophysical data on the Amirante Arc, which locates to the south of the Seychelles Islands, are presented. These data were obtained by Pacific Oceanological Institute during the 33-rd cruise of R/V Professor Bogorov in 1990. The Amirante Arc represents a seamount chain, which has submeridional strike and total length about 400 km. To the west of the Amirante Arc there are a deep sea trench and a back-arc basin, i.e. this area is characterized by structural elements associated with the subduction zone of Western Pacific type. According to our data the Amirante Arc is composed by tholeiites of ocean plateau type. This facts are evidences that the Amirante Arc differs from typical Pacific island arcs. This gives an opportunity to distinguish a special type of oceanic structures, i.e. non-volcanic (amagmatic) ridges. The Amirante Ridge has been probably formed as a result of oceanic crust heaping due to horizontal displacements of its blocks in the process of spreding ridge formation in the Indian Ocean during Cretaceous-Paleogene.

Sedimentary and subsidence history of ODP Sites 135-840 and 135-841

Sedimentary sections recovered from the Tonga platform and forearc during Ocean Drilling Program Leg 135 provide a record of the sedimentary evolution of the active margin of the Indo-Australian Plate from late Eocene time to the Present. Facies analyses of the sediments, coupled with interpretations of downhole Formation MicroScanner logs, allow the complete sedimentary and subsidence history of each site to be reconstructed. After taking into account the water depths in which the sediments were deposited and their subsequent compaction, the forearc region of the Tofua Arc (Site 841) can be seen to have experienced an initial period of tectonic subsidence dating from 35.5 Ma. Subsidence has probably been gradual since that time, with possible phases of accelerated subsidence, starting at 16.2 and 10.0 Ma. The Tonga Platform (Site 840) records only the last 7.0 Ma of arc evolution. However, the increased accuracy of paleowater depth determinations possible with shallow-water platform sediments allows the resolution of a distinct increase in subsidence rates at 5.30 Ma. Thus, sedimentology and subsidence analyses show the existence of at least two, and possibly four, separate subsidence events in the forearc region. Subsidence dating from 35.5 Ma is linked to rifting of the South Fiji Basin. Any subsidence dating from 16.2 Ma at Site 841 does not correlate with another known tectonic event and is perhaps linked to localized extensional faulting related to slab roll back during steady-state subduction. Subsidence from 10.0 Ma coincides with the breakup of the early Tertiary Vitiaz Arc because of the subduction polarity reversal in the New Hebrides and the subsequent readjustment of the plate boundary geometry. More recently, rapid subsidence and deposition of a upward-fining cycle from 5.30 Ma to the Present at Site 840 is thought to relate to rifting of the Lau Basin. Sedimentation is principally controlled by tectonic activity, with variations in eustatic sea level playing a significant, but subordinate role. Subduction of the Louisville Seamount Chain seems to have disrupted the forearc region locally, although it had only a modest effect on the subsidence history and sedimentation of the Tonga Platform as a whole.

Rare-earth elements and isotope ratios at DSDP Leg 82 Holes

We report 48 analyses of rare-earth elements (REE) and 15 143Nd/144Nd and 87Sr/86Sr analyses for basalts from the eight holes drilled during Leg 82. Discrete and distinct REE patterns and 143Nd/144Nd ratios characterize the eight holes, with little variation observed downhole except in Holes 561 and 558, thus suggesting dominantly long-term temporal and large-scale spatial variations in the mantle source of these basalts beneath the Mid-Atlantic Ridge over the last 35 Ma of its spreading activity. There is a good inverse correlation between 143Nd/144Nd and (La/Sm)EF with one exception in Hole 558 (approximately 35 Ma), the latter suggesting a recent (35 Ma) light REE depletion event, perhaps caused by dynamic or fractional melting. Short-term temporal and small-scale spatial mantle source variability is also evident in Hole 561 (approximately 18 Ma), which has rapid fluctuations in REE patterns and 143Nd/144Nd ratios (suggesting rapid transfer of magma from the time of melting) and is evidence contrary to the presence of a well-mixed magma chamber at this particular site and time. The mantle source variations noted can be interpreted within two extreme models. The first model invokes a convecting mantle depleted in large ion lithophile elements (LILE) and containing lumps (or veins) of LILE-enriched material of various shapes and sizes, passively and randomly distributed throughout. A second more restrictive model considers the interaction of fixed mantle plumes and the LILE-depleted asthenosphere flowing towards a migrating Mid- Atlantic Ridge (MAR) axis. With the exception of Hole 558 and the uncertainties of reconstructions of absolute plate movements in the region, the observed variations can be explained by two hot spots; the nearly ridge-centered Azores hot spot (plume) and another hot spot located beneath the African plate that may be affecting the source of basalts currently erupting at the MAR axis at 35°N and which, in the past, would have produced the New England chain of seamounts on the North American plate and (later) the Atlantis-Great Meteor chain on the African plate. Basalts erupted south of the Hayes Fracture Zone have not been affected by either of these two hot spots over the last 35 Ma and appear to have been continuously derived from the LILE-depleted source. Subaxial flow downridge from the Azores plume appears to have started 9 Ma, on the basis of the southward converging V-shaped time-transgressive ridges branching from the Pico and Corves Island, or not earlier than 16 Ma, on the basis of the geochemical results. Variations within Hole 558 remains unexplained by the latter model, unless we hypothesize a third hot spot.

Short nomenclator or vocabular in English and Hebrew: composed alphabetically for the use and benefit of my pupils in particular and for the advantage of those who are desirous to obtain the knowledge of the Hebrew tongue in general, which may be that great help to understand not only ye sacred oracles in their original, but even any Jewish author (so far as concern owns) as also it may give great insight in ye tongue to those, as to compose it, a work altogether new, [ca. 1735]

Headed on the first page with the words "Nomenclatura hebraica," this handwritten volume is a vocabulary with the Hebrew word in the left column, and the English translation on the right. While the book is arranged in sections by letter, individual entries do not appear in strict alphabetical order. The small vocabulary varies greatly and includes entries like enigma, excommunication, and martyr, as well as cucumber and maggot. There are translations of the astrological signs at the end of the volume. Poem written at the bottom of the last page in different hand: "Women when good the best of saints/ that bright seraphick lovely/ she, who nothing of an angel/ wants but truth & immortality./ Verse 2: Who silken limbs & charming/ face. Keeps nature warm."

Coastal Massachusetts, Marblehead to Hampton Harbor, New Hampshire, Nautical Chart, 1776 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [A chart of the harbours of Hampton, Newbury, Ipswich, Jebeka, Squam, Cape Ann, Manchester, Beverly, Salem, Marble Head &c.] (sheet originally published in 1776). The map is [sheet 23] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:50,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Covers coastal Massachusetts from Ipswich Harbor to Marblehead. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar 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 coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns, buildings, and roads. Relief is shown by hachures; depths by soundings. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.

Coastal Massachusetts, Marblehead to Hampton Harbor, New Hampshire, Nautical Chart, 1776 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [A chart of the harbours of Hampton, Newbury, Ipswich, Jebeka, Squam, Cape Ann, Manchester, Beverly, Salem, Marble Head &c.] (sheet originally published in 1776). The map is [sheet 24] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:50,000]. This layer is image 2 of 2 total images of the two sheet source map, representing the northern portion of the map. Covers coastal Massachusetts and New Hampshire from Ipswich Harbor, Massachusetts to Hampton Harbor, New Hampshire. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar 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 coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns, buildings, and roads. Relief is shown by hachures; depths by soundings. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.

Portsmouth Harbor and Piscataqua River, New Hampshire and Maine, Nautical Chart, 1779 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [A chart of Piscataqua Harbour] (sheet originally published in 1779). The map is [sheet 32] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:25,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Covers coast of New Hampshire from North Beach to Portsmouth. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar 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 coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns, buildings, and roads. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.

Portsmouth Harbor and Piscataqua River, New Hampshire and Maine, Nautical Chart, 1779 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [A chart of Piscataqua Harbour] (sheet originally published in 1779). The map is [sheet 33] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:25,000]. This layer is image 2 of 2 total images of the two sheet source map, representing the northern portion of the map. Covers coast of New Hampshire and Maine, from Portsmouth, New Hampshire to York Harbor, Maine. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar 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 coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns, buildings, and roads. Relief is shown by hachures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.