The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia

The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension1, 2, 3. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension

Facilitating interaction and retrieval for annotated documents

Digital annotation of web pages presents new problems connected to the dynamics and the openness of the web. First, the variety of available browsers may require the use of proprietary solutions, once one goes beyond traditional interaction with hyperlinks. Second, documents are replicated over multiple sites and can be retrieved at different URLs or with different queries. Hence, annotations on a web content must be retrieved even if they were created while accessing the same content under a different URL. Moreover, when pages are modified, annotations related to fragments that have moved within the page itself should be retrieved and shown to the user. We have improved the MADCOW annotation system with a uniform interaction paradigm and incorporated two algorithms: one to assess the identity of two pages under two different URLs and the other to identify variations in two versions of a page under the same URL. Copyright © 2010 Inderscience Enterprises Ltd

Satellite and in situ measurements for coastal water quality assessmentand monitoring: a comparison between MODIS Ocean Color and SSTproducts with Wave Glider observations in the Southern Tyrrhenian Sea(Gulf of Naples, Italy).

A wave-propelled autonomous vehicle (Wave Glider, WG) carrying a variety of oceanographic and meteorological sensors was launched from Gulf of Naples on the 12th September 2012 for a three-week mission in the Southern Tyrrhenian Sea. The main objective of the mission was the opportunity to evaluate the usefulness of combined satellite and autonomous platform observations in providing reliable and concurrent information about sea wa-ter parameters about the Southern Tyrrhenian Sea surface layer. The Wave Glider was equipped with sensors tomeasure temperature, salinity, currents, as well as CDOM, turbidity and refined fuels fluorescence. Wave Glider oceanographic data were also compared to satellite measurements. In particular, MODIS Ocean Color (OC) prod-ucts concerning sea water properties collected during the Wave Glider mission were used. The EOS constellation allowed us to have about two daily diurnal imagery providing information about ocean color products. Concerning SST, both diurnal and night-time data were available. The first study we performed was focused on the analysis ofSST information coming from both WG and MODIS. A good coefficient of correlation was achieved consideringtogether both day-time and night-time acquisitions, with a discrepancy not higher than 0,7◦C. The correlation increases considering only day-time values, when more samples respect to the night-time ones were available. The results confirm the capability of MODIS products to reproduce over large area the SST variability, with agood level of accuracy. A similar analysis has been carried out to compare the turbidity WG data with the kd-490MODIS product, which provide information about the diffuse attenuation coefficient in water at 490 nm and it isdirectly related to the presence of scattering particles, either organic or inorganic, in the water column and thus itis an indication of water clarity or of the water column turbidity. The absence of correlation seems to indicate, forsuch a specific parameter, that the two sensors are looking at not similar objects. A different depth of investigation or a small scale variability, that MODIS is not able to capture, could be a few of the explanations of these results.It should be also stressed that, by its design, the WG is propelled at the surface like a surfboard and bubbles ofall sizes will roll along the bottom of the float. Microbubbles are of particular concern since they will not rapidly ascend and are likely to represent a source noise for the turbidity WG parameter. Finally, the refined fuels WG datahave been compared with a statistical indicator of oil spill presence named RST-OIL and the correlation was quitepoor. Such a results is quite expected since for its construction, values of RETIRAbox within +/-2σ, like those achieved along WG path, have a probability of occurrence of 97,75% representing the normal fluctuation of thesignal, hence randomly varying

Regeneration of acinar cells following ligation of rat submandibular gland retraces the embryonic-perinatal pathway of cytodifferentiation

Rat submandibular gland can regenerate following ligation-induced atrophy, eventually recovering its normal morphology and function. Previous studies have suggested that the regeneration process implies both self-proliferation of existing acini and formation of new acinar cells. One hypothesis is that new acinar cells may differentiate from the ductal cells in a similar fashion to the process of cytodifferentiation occurring during submandibular glandular development. In this study atrophy was induced, under recovery anaesthesia, by applying a metal clip on the main duct of the submandibular gland without including the chorda lingual nerve. After 2 weeks the duct was deligated for 3, 5 or 7 days or 8 weeks and the glands collected. Tissue was prepared for immunohistochemstry, biochemical analysis and RNA extraction. The histology of the regenerated glands shows several normal-looking acini, which have regained their glycoprotein content (AB/PAS positive), data also confirmed by biochemical analysis (SDS-PAGE/PAS). Regenerating tissue was characterized by the presence of embryonic-like branched structures ending with AB/PAS positive acinar cells. The proteins SMG-B and PSP are normally expressed in acinar cell precursors during development but only by intercalated ductal cells in the adult stage. In the adult regenerating gland mRNA levels of both SMG-B and PSP were found to be up-regulated compared to ligated glands and SMG-B expression localized to acinar cells whilst the ductal cells were negative. This study of rat submandibular gland regeneration suggests new acinar cells have differentiated from ducts and express markers of acinar cell precursors in a similar manner to the cytodifferentiation process occurring during glandular development