Urinary pyridinoline cross-links as biomarkers of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a group of genetic heterogeneous connective tissue disorders characterized by increased bone fragility and susceptibility to fractures. Laboratory diagnosis relies on time-consuming and cost-intensive biochemical and molecular genetics analyses. Therefore, it is desirable to identify and establish new diagnostic markers for OI that are reliable, cost-effective and easily accessible. In our study we have identified the ratio of the urinary pyridinoline cross-links lysyl-pyridinoline and hydroxylysyl-pyridinoline as a promising, time- and cost-effective biomarker for osteogenesis imperfecta, that could be used furthermore to investigate cases of suspected non-accidental injury in infants

Marine and continental aerosol effects on the upwelling solar radiation flux in Southern Portugal during the ACE-2 experiment

n/

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Marine and continental aerosol effects on the upwelling solar radiation flux in Southern Portugal during the ACE-2 experiment

An overall number of 447 spectral series of aerosol optical depth were determined in the 0.4-3.7 mm wavelength range by examining the IR-RAD sun-radiometer measurements carried out at Sagres (Portugal) on six clear-sky days, during the CLEARCOLUMN (ACE-2) experiment in June and July 1997. These spectral series were then analysed with the King inversion method to defi ne the size-distribution curves of columnar aerosol particle total number and volume, assuming values of both real and imaginary parts of the particulate refractive index obtained on the six days by combining our measurements with simultaneous sky-brightness measurements taken by the Leipzig University group. For these results, we then calculated the daily time-patterns of the average single scattering albedo of the columnar aerosols, fi nding instantaneous values ranging between 0.70 and 0.96 on those days, with daily mean values varying from 0.83 to 0.95. Furthermore, for each spectral series of aerosol optical depth, we determined the instantaneous change DF^ induced by the columnar aerosols on the upwelling solar radiation fl ux leaving the atmosphere, over oceanic areas presenting low surface albedo. The 24-h average values of DF^ obtained on the six days were found to increase as a function of the daily mean value of aerosol optical depth at the 0.55 mm wavelength, following relationship curves whose positive slope coeffi cients decrease gradually with the single scattering albedo of the columnar aerosols. The said curves can be used to achieve reliable estimates of change DF^ directly from daily ground-based multispectral measurements of aerosol optical depth and skybrightness at different angular distances from the Sun.An overall number of 447 spectral series of aerosol optical depth were determined in the 0.4-3.7 mm wavelength range by examining the IR-RAD sun-radiometer measurements carried out at Sagres (Portugal) on six clear-sky days, during the CLEARCOLUMN (ACE-2) experiment in June and July 1997. These spectral series were then analysed with the King inversion method to defi ne the size-distribution curves of columnar aerosol particle total number and volume, assuming values of both real and imaginary parts of the particulate refractive index obtained on the six days by combining our measurements with simultaneous sky-brightness measurements taken by the Leipzig University group. For these results, we then calculated the daily time-patterns of the average single scattering albedo of the columnar aerosols, fi nding instantaneous values ranging between 0.70 and 0.96 on those days, with daily mean values varying from 0.83 to 0.95. Furthermore, for each spectral series of aerosol optical depth, we determined the instantaneous change DF^ induced by the columnar aerosols on the upwelling solar radiation flux leaving the atmosphere, over oceanic areas presenting low surface albedo. The 24-h average values of DF^ obtained on the six days were found to increase as a function of the daily mean value of aerosol optical depth at the 0.55 mm wavelength, following relationship curves whose positive slope coeffi cients decrease gradually with the single scattering albedo of the columnar aerosols. The said curves can be used to achieve reliable estimates of change DF^ directly from daily ground-based multispectral measurements of aerosol optical depth and skybrightness at different angular distances from the Sun

Atmospheric Brown Clouds in the Himalayas: first two years of continuous observations at the Nepal Climate Observatory-Pyramid (5079 m)

This paper provides a detailed description of the atmospheric conditions characterizing the high Himalayas, thanks to continuous observations begun in March 2006 at the Nepal Climate Observatory-Pyramid (NCO-P) located at 5079 m a.s.l. on the southern foothills of Mt. Everest, in the framework of ABC-UNEP and SHARE-Ev-K2-CNR projects. The work presents a characterization of meteorological conditions and air-mass circulation at NCO-P during the first two years of activity. The mean values of atmospheric pressure, temperature and wind speed recorded at the site were: 551 hPa, −3.0 °C, 4.7 m s−1, respectively. The highest seasonal values of temperature (1.7 °C) and relative humidity (94%) were registered during the monsoon season, which was also characterized by thick clouds, present in about 80% of the afternoon hours, and by a frequency of cloud-free sky of less than 10%. The lowest temperature and relative humidity seasonal values were registered during winter, −6.3 °C and 22%, respectively, the season being characterised by mainly cloud-free sky conditions and rare thick clouds. The summer monsoon influenced rain precipitation (seasonal mean: 237 mm), while wind was dominated by flows from the bottom of the valley (S–SW) and upper mountain (N–NE). The atmospheric composition at NCO-P has been studied thanks to measurements of black carbon (BC), aerosol scattering coefficient, PM1, coarse particles and ozone. The annual behaviour of the measured parameters shows the highest seasonal values during the pre-monsoon (BC: 316.9 ng m−3, PM1: 3.9 μg m−3, scattering coefficient: 11.9 Mm−1, coarse particles: 0.37 cm−3 and O3: 60.9 ppbv), while the lowest concentrations occurred during the monsoon (BC: 49.6 ng m−3, PM1: 0.6 μg m−3, scattering coefficient: 2.2 Mm−1, and O3: 38.9 ppbv) and, for coarse particles, during the post-monsoon (0.07 cm−3. At NCO-P, the synoptic-scale circulation regimes present three principal contributions: Westerly, South-Westerly and Regional, as shown by the analysis of in-situ meteorological parameters and 5-day LAGRANTO back-trajectories. The influence of the brown cloud (AOD>0.4) extending over Indo–Gangetic Plains up to the Himalayan foothills has been evaluated by analysing the in-situ concentrations of the ABC constituents. This analysis revealed that brown cloud hot spots mainly influence the South Himalayas during the pre-monsoon, in the presence of very high levels of atmospheric compounds (BC: 1974.1 ng m−3, PM1: 23.5 μg m−3, scattering coefficient: 57.7 Mm−1, coarse particles: 0.64 cm−3, O3: 69.2 ppbv, respectively). During this season 20% of the days were characterised by a strong brown cloud influence during the afternoon, leading to a 5-fold increased in the BC and PM1 values, in comparison with seasonal means. Our investigations provide clear evidence that, especially during the pre-monsoon, the southern side of the high Himalayan valleys represent a "direct channel" able to transport brown cloud pollutants up to 5000 m a.s.l., where the pristine atmospheric composition can be strongly influenced.ISSN:1680-7375ISSN:1680-736