Limitaciones de la asistencia orientada al desarrollo en Uganda

En los asentamientos tipo campamento, la asistencia brindada por las agencias de ayuda que tienen una orientación al desarrollo puede hacer poco más que mejorar las condiciones de vida.

First steps toward harmonized human biomonitoring in Europe : demonstration project to perform human biomonitoring on a European scale

'Reproduced with permission from Environmental Health Perspectives'

Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth.

Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked to an increased risk of melanoma. Here, we have examined the potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination of biochemical assays and real-time monitoring of melanoma cells, we report a cGMP-dependent growth-promoting pathway in murine and human melanoma cells. We document that C-type natriuretic peptide (CNP), a ligand of the membrane-bound guanylate cyclase B, enhances the activity of cGMP-dependent protein kinase I (cGKI) in melanoma cells by increasing the intracellular levels of cGMP. Activation of this cGMP pathway promotes melanoma cell growth and migration in a p44/42 MAPK-dependent manner. Sildenafil treatment further increases intracellular cGMP concentrations, potentiating activation of this pathway. Collectively, our data identify this cGMP-cGKI pathway as the link between sildenafil usage and increased melanoma risk.

Phorbol-12-myristate-13-acetate induces nociceptin in human Mono Mac 6 cells via multiple transduction signalling pathways.

BACKGROUND Nociceptin in the peripheral circulation has been proposed to have an immunoregulatory role with regards to inflammation and pain. However, the mechanisms involved in its regulation are still not clear. The aim of this study was to investigate signalling pathways contributing to the regulation of the expression of nociceptin under inflammatory conditions. METHODS Mono Mac 6 cells (MM6) were cultured with or without phorbol-12-myristate-13-acetate (PMA). Prepronociceptin (ppNOC) mRNA was detected by RT-qPCR and extracellular nociceptin by fluorescent-enzyme immunoassay. Intracellular nociceptin and phosphorylated kinases were measured using flow cytometry. To evaluate the contribution of various signalling pathways to the regulation of ppNOC mRNA and nociceptin protein, cells were pre-treated with specific kinase inhibitors before co-culturing with PMA. RESULTS ppNOC mRNA was expressed in untreated MM6 at low concentrations. Exposure of cells to PMA upregulated ppNOC after nine h compared with controls without PMA (median normalized ratio with IQR: 0.18 (0.15-0.26) vs. 0 (0-0.02), P<0.01). Inhibition of mitogen-activated protein kinases specific for signal transduction reversed the PMA effects (all P<0.001). Induction of nociceptin protein concentrations in PMA stimulated MM6 was prevented predominantly by identity of ERK inhibitor (P<0.05). CONCLUSIONS Upregulation of nociceptin expression by PMA in MM6 cells involves several pathways. Underlying mechanisms involved in nociceptin expression may lead to new insights in the treatment of pain and inflammatory diseases.

Elektrophysiologische Effekte einer superoseptalen Ablationslinie als Alternative zu einer Mitralisthmus-Ablationslinie während Katheterablation bei Patienten mit lang anhaltendem paroxysmalem bzw. persistierendem Vorhofflimmern

Universität Magdeburg, Dissertation, 2016

Stable isotopes, Mg/Ca-ratios, and biogenic opal of five sediment cores from the subarctic northwest Pacific

Based on models and proxy data it has been proposed that salinity-driven stratification weakened in the subarctic North Pacific during the last deglaciation, which potentially contributed to the deglacial rise in atmospheric carbon dioxide. We present high-resolution subsurface temperature (TMg/Ca) and subsurface salinity-approximating (d18Oivc-sw) records across the last 20,000 years from the subarctic North Pacific and its marginal seas, derived from combined stable oxygen isotopes and Mg/Ca ratios of the planktonic foraminiferal species Neogloboquadrina pachyderma (sin.). Our results indicate regionally differing changes of subsurface conditions. During the Heinrich Stadial 1 and the Younger Dryas cold phases our sites were subject to reduced thermal stratification, brine rejection due to sea-ice formation, and increased advection of low-salinity water from the Alaskan Stream. In contrast, the Bølling-Allerød warm phase was characterized by strengthened thermal stratification, stronger sea-ice melting, and influence of surface waters that were less diluted by the Alaskan Stream. From direct comparison with alkenone-based sea surface temperature estimates (SSTUk'37), we suggest deglacial thermocline changes that were closely related to changes in seasonal contrasts and stratification of the mixed layer. The modern upper-ocean conditions seem to have developed only since the early Holocene.

Fluid compositions and mineralogy of precipitates from Mid Atlantic Ridge hydrothermal vents at 4°48'S

The effect of volcanic activity on submarine hydrothermal systems has been well documented along fast- and intermediate-spreading centers but not from slow-spreading ridges. Indeed, volcanic eruptions are expected to be rare on slow-spreading axes. Here we report the presence of hydrothermal venting associated with extremely fresh lava flows at an elevated, apparently magmatically robust segment center on the slow-spreading southern Mid-Atlantic Ridge near 5°S. Three high-temperature vent fields have been recognized so far over a strike length of less than 2 km with two fields venting phase-separated, vapor-type fluids. Exit temperatures at one of the fields reach up to 407°C, at conditions of the critical point of seawater, the highest temperatures ever recorded from the seafloor. Fluid and vent field characteristics show a large variability between the vent fields, a variation that is not expected within such a limited area. We conclude from mineralogical investigations of hydrothermal precipitates that vent-fluid compositions have evolved recently from relatively oxidizing to more reducing conditions, a shift that could also be related to renewed magmatic activity in the area. Current high exit temperatures, reducing conditions, low silica contents, and high hydrogen contents in the fluids of two vent sites are consistent with a shallow magmatic source, probably related to a young volcanic eruption event nearby, in which basaltic magma is actively crystallizing. This is the first reported evidence for direct magmatic-hydrothermal interaction on a slow-spreading mid-ocean ridge.