The p53 isoforms are differentially modified by Mdm2

The discovery that the single p53 gene encodes several different p53 protein isoforms has initiated a flurry of research into the function and regulation of these novel p53 proteins. Full-length p53 protein level is primarily regulated by the E3-ligase Mdm2, which promotes p53 ubiquitination and degradation. Here, we report that all of the novel p53 isoforms are ubiquitinated and degraded to varying degrees in an Mdm2-dependent and -independent manner, and that high-risk human papillomavirus can degrade some but not all of the novel isoforms, demonstrating that full-length p53 and the p53 isoforms are differentially regulated. In addition, we provide the first evidence that Mdm2 promotes the NEDDylation of p53β. Altogether, our data indicates that Mdm2 can distinguish between the p53 isoforms and modify them differently.     

ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates.Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28).Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions.Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.     

The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections

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Vegetation fluctuation in mediterranean dune ponds in relation to rainfall variation and water extraction

Abstract. The structure of dune ponds hygrophytic vegetation has a spatial organisation in belts around the pond basin, closely related to water level and flooding regime. Doñana National Park has an important representation of temporal dune ponds, which are subjected to rainfall fluctuations and may be suffering the impact of water extraction from the neighbouring tourist resort. Permanent transects in a vegetation complex of five dune ponds have been monitored during a eight year period (1990-1997). This period was characterised by a number of dry years (annual rainfall around 300 mm), located between two wet cycles (800-900 mm). Transects were analysed in 1990 (wet period), 1994 (dry) and 1997 (wet) by hierarchical agglomera-tive clustering. During the dry period hygrophytic species showed regression, with a high mortality of some species like Ulex minor, while the xerophytic species advanced to lower areas. Seedlings of some xerophytic species colonised the dry surface of the pond basin. The lowering of the water table varied in the different ponds, ranging from 312 to 190 cm depending on topography and the distance to the pumping area. The new period of flooding during 1995-96 and 1996-97 cycles provided the opportunity for hygrophytic spe cies to re-establish themselves in their original places. This study suggest that changes in vegetation are caused by the interaction between weather conditions and human disturbance (water extractions). In our example man-made disturbance is more marked during the dry periods while wet periods tend to obscure the effects of water extractions. From a management perspective, long-term monitoring of water table and vegetation structure is revealed as a key procedure to the management of land-water ecotones on pressured areas and threatened habitats.     

Effect of tower base painting on willow ptarmigan collision rates with wind turbines

1. Birds colliding with turbine rotor blades is a well‐known negative consequence of wind‐power plants. However, there has been far less attention to the risk of birds colliding with the turbine towers, and how to mitigate this risk.
2. Based on data from the Smøla wind‐power plant in Central Norway, it seems highly likely that willow ptarmigan (the only gallinaceous species found on the island) is prone to collide with turbine towers. By employing a BACI‐approach, we tested if painting the lower parts of turbine towers black would reduce the collision risk.
3. Overall, there was a 48% reduction in the number of recorded ptarmigan carcasses per search at painted turbines relative to neighboring control (unpainted) ones, with significant variation both within and between years.
4. Using contrast painting to the turbine towers resulted in significantly reduced number of ptarmigan carcasses found, emphasizing the effectiveness of such a relatively simple mitigation measure.

     

KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling

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Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells

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Terpenoid and morphological variability of Pinus quadrifolia and the natural hybridization with Pinus monophylla in the San Jacinto Mountains in California

Monoterpenoids from wood of Pinus quadrifolia and Pinus monophylla from south of the San Jacinto Mountains in southern California were analysed by gas-liquid chromatography (GLC). The number of needles per fascicle, the number of resin canals, and the number of abaxial and adaxial stomatal rows in the needles were determined. Percentages of mycrene, α-pinene, and to a minor extent of camphene, β-pinene, limonene, and β-phellandrene, the above mentioned morphological characteristics and previously obtained data were all used for identification and characterisation of species intermediacy in the San Jacinto area. It was concluded that many P. quadrifolia trees in the mixed Buck Ridge stand and some trees in two pure stands of the same area were hybrids and that sympatric and to a lesser extent allopatric introgression of P. monophylla into P. quadrifolia takes place in the San Jacinto region. Introgression of P. quadrifolia into P. monophylla could not be demonstrated.