Photosynthesis responses to ozone in young trees of three species with different sensitivities, in a 2-year open-top chamber experiment (Curno, Italy)

This paper reports the findings of an open-top chamber experiment carried out in northern Italy (Forest nursery at Curno), during the 2004 and 2005 growth seasons, on Fagus sylvatica and Quercus robur seedlings and on Populus nigra cuttings, in order to test their photosynthesis response to ambient ozone. The experimental protocols were non-filtered air (NF), charcoal-filtered air (CF) and open air (OA). Tests performed included morphological features of leaves; development of foliar symptoms; chlorophyll content, determined by non-destructive means; chlorophyll fluorescence (direct fluorescence and JIP test) and gas exchanges and net photosynthesis (P_N). Main findings were as follows: (1) symptoms occurred early and were extensive in P. nigra , and they occurred later in F. sylvatica , whereas early degeneration of chlorophyll occurred in late summer in Q. robur ; (2) in conditions of ozone exposure, the three species all presented a decline in photosynthesis efficiency and a decrease in P_N, regardless of the symptomatology they displayed; (3) leaf traits are predictors of species-specific sensitivity to ozone—the high density of Q. robur foliar tissues prevents this species from developing visible symptoms and reduces the extent of physiological responses and (4) physiological responses varied from year to year in the same species—responses were lower in the second year of the experiment, when plants had become better acclimatized to plot conditions.     

Stabilization of telomeres in nonlinear models of proliferating cell lines

We analyse an age-structured model of telomere loss in a proliferating cell population. The cell population is divided into telomere classes, which shorten each round of division. The model consists of a nonlinear system of partial differential equations for the telomere classes. We prove that if the highest telomere class is exempted from mortality, then all the classes stabilize to a nontrivial equilibrium dependent on the initial state of cells in the highest telomere class.     

The conformational and property space of acetylcholine bound to muscarinic receptors: an entropy component accounts for the subtype selectivity of acetylcholine

The conformational behavior of receptor-bound acetylcholine (ACh) was investigated by molecular dynamics simulations. Based on the great similarity among muscarinic receptors, the study was focused on the human M(1), M(2), and M(5) receptors as previously modeled by us. The results showed that receptor-bound ACh was not frozen in a single preferred conformation but preserved an unexpected fraction of its conformational space. However, there were marked differences between the three receptors since the ligand was mostly trans in the M(1) receptor, equally distributed among trans and gauche conformers in M(2), and exclusively gauche in the M(5); the greater flexibility of M(2)-bound ACh was paralleled by the greater flexibility of the occupied M(2) binding site. By contrast, the property space of receptor-bound ACh, and particularly its virtual (computed, conformation-dependent) lipophilicity, was restricted to relatively narrow ranges optimal for successful interaction. Experimental binding investigations to the individual human M(1), M(2), and M(5) muscarinic receptors showed ACh to have a 10-fold higher affinity for the M(2) compared to the M(1) and M(5) receptors. This selectivity was not confirmed by the calculated binding scores, a fact postulated to be caused by the absence of an entropy component in such binding scores. Indeed, the Shannon entropy of all geometric and physicochemical properties monitored were markedly higher in M(2)-bound ACh compared to M(1)-bound and M(5)-bound ACh. This finding suggests that the selectivity profile of acetylcholine for the M(2) receptor is largely entropy-driven, a fact that might explain the intrinsic difficulty to design subtype-selective muscarinic agonists.     

Twenty-four novel mutations in Wilson disease patients of predominantly Italian origin

Herein we report the results of mutation analysis of the ATP7B gene in a group of 134 Wilson disease (WD) families (268 chromosomes) prevalently of Italian origin. Using the SSCP and sequencing methods we identified 71 disease-causing mutations. Twenty-four were novel, while 19 more mutations already described, were identified in new populations in this study. A known mutation G591D showed a regional distribution, since it was only detected in 38.5% of the analyzed chromosomes in WD patients originating from Apulia, a region of South Italy. Detection of new mutations in the ATP7B gene increases our capability of molecular analysis that is essential for early diagnosis and treatment of WD.     

cAMP induced alterations of Chinese hamster ovary cells monitored by mass spectrometry

Chinese Hamster Ovary fibroblasts (CHO-K1) have shown different protein contents when undergoing differentiation by 3',5'-cyclic adenosine monophosphate (cAMP), which is known to induce reverse transformation (RT) from malignancy to fibroblast-like characteristics. The mass spectrometry (MS) investigation here reported about the behavior of CHO-K1 cells before and after exposure to cAMP reveals a change in the composition of nuclear proteins associated to an inhibition of the protein expression. Possible implications of this finding on the control of cell reverse transformation are discussed.     

Symmetrical Dose-Dependent DNA-Methylation Profiles in Children with Deletion or Duplication of 7q11.23

Epigenetic dysfunction has been implicated in a growing list of disorders that include cancer, neurodevelopmental disorders, and neurodegeneration. Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7) are rare neurodevelopmental disorders with broad phenotypic spectra caused by deletion and duplication, respectively, of a 1.5-Mb region that includes several genes with a role in epigenetic regulation. We have identified striking differences in DNA methylation across the genome between blood cells from children with WS or Dup7 and blood cells from typically developing (TD) children. Notably, regions that were differentially methylated in both WS and Dup7 displayed a significant and symmetrical gene-dose-dependent effect, such that WS typically showed increased and Dup7 showed decreased DNA methylation. Differentially methylated genes were significantly enriched with genes in pathways involved in neurodevelopment, autism spectrum disorder (ASD) candidate genes, and imprinted genes. Using alignment with ENCODE data, we also found the differentially methylated regions to be enriched with CCCTC-binding factor (CTCF) binding sites. These findings suggest that gene(s) within 7q11.23 alter DNA methylation at specific sites across the genome and result in dose-dependent DNA-methylation profiles in WS and Dup7. Given the extent of DNA-methylation changes and the potential impact on CTCF binding and chromatin regulation, epigenetic mechanisms most likely contribute to the complex neurological phenotypes of WS and Dup7. Our findings highlight the importance of DNA methylation in the pathogenesis of WS and Dup7 and provide molecular mechanisms that are potentially shared by WS, Dup7, and ASD.