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101.
Cristina Lanni Lavinia Nardinocchi Rosa Puca Serena Stanga Daniela Uberti Maurizio Memo Stefano Govoni Gabriella D'Orazi Marco Racchi 《PloS one》2010,5(4)
Background
Homeodomain interacting protein kinase 2 (HIPK2) is an evolutionary conserved serine/threonine kinase whose activity is fundamental in maintaining wild-type p53 function, thereby controlling the destiny of cells when exposed to DNA damaging agents. We recently reported an altered conformational state of p53 in tissues from patients with Alzheimer''s Disease (AD) that led to an impaired and dysfunctional response to stressors.Methodology/Principal Findings
Here we examined the molecular mechanisms underlying the impairment of p53 activity in two cellular models, HEK-293 cells overexpressing the amyloid precursor protein and fibroblasts from AD patients, starting from recent findings showing that p53 conformation may be regulated by HIPK2. We demonstrated that beta-amyloid 1–40 induces HIPK2 degradation and alters HIPK2 binding activity to DNA, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus. Expression of HIPK2 was analysed by western blot experiments, whereas HIPK2 DNA binding was examined by chromatin immunoprecipitation analysis. In particular, we evaluated the recruitment of HIPK2 onto some target promoters, including hypoxia inducible factor-1α and metallothionein 2A.Conclusions/Significance
These results support the existence of a novel amyloid-based pathogenetic mechanism in AD potentially leading to the survival of injured dysfunctional cells. 相似文献102.
Giovanni Bacci Patrizia Paganin Loredana Lopez Chiara Vanni Claudia Dalmastri Cristina Cantale Loretta Daddiego Gaetano Perrotta Daniela Dolce Patrizia Morelli Vanessa Tuccio Alessandra De Alessandri Ersilia Vita Fiscarelli Giovanni Taccetti Vincenzina Lucidi Annamaria Bevivino Alessio Mengoni 《PloS one》2016,11(6)
Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF. 相似文献
103.
Cristina Botella M. ángeles Pérez-Ara Juana Bretón-López Soledad Quero Azucena García-Palacios Rosa María Ba?os 《PloS one》2016,11(2)
Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. “One-session treatment” guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants’ expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants. 相似文献
104.
Ghezzi D Baruffini E Haack TB Invernizzi F Melchionda L Dallabona C Strom TM Parini R Burlina AB Meitinger T Prokisch H Ferrero I Zeviani M 《American journal of human genetics》2012,90(6):1079-1087
Dysfunction of mitochondrial respiration is an increasingly recognized cause of isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin of this condition, we used next-generation exome sequencing to identify mutations in MTO1, which encodes mitochondrial translation optimization 1. Two affected siblings carried a maternal c.1858dup (p.Arg620Lysfs∗8) frameshift and a paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual was homozygous for the latter change. In both humans and yeast, MTO1 increases the accuracy and efficiency of mtDNA translation by catalyzing the 5-carboxymethylaminomethylation of the wobble uridine base in three mitochondrial tRNAs (mt-tRNAs). Accordingly, mutant muscle and fibroblasts showed variably combined reduction in mtDNA-dependent respiratory chain activities. Reduced respiration in mutant cells was corrected by expressing a wild-type MTO1 cDNA. Conversely, defective respiration of a yeast mto1Δ strain failed to be corrected by an Mto1Pro622∗ variant, equivalent to human MTO1Arg620Lysfs∗8, whereas incomplete correction was achieved by an Mto1Ala431Thr variant, corresponding to human MTO1Ala428Thr. The respiratory yeast phenotype was dramatically worsened in stress conditions and in the presence of a paromomycin-resistant (PR) mitochondrial rRNA mutation. Lastly, in vivo mtDNA translation was impaired in the mutant yeast strains. 相似文献
105.
Sanfélix Javier Mathieux Fabrice de la Rúa Cristina Wolf Marc-Andree Chomkhamsri Kirana 《The International Journal of Life Cycle Assessment》2013,18(1):273-277
The International Journal of Life Cycle Assessment - To support life cycle-based EU policies, the European Commission created the “European Platform on Life Cycle Assessment (EPLCA).”... 相似文献
106.
Steven T. Staben Timothy P. Heffron Daniel P. Sutherlin Seema R. Bhat Georgette M. Castanedo Irina S. Chuckowree Jenna Dotson Adrian J. Folkes Lori S. Friedman Leslie Lee John Lesnick Cristina Lewis Jeremy M. Murray Jim Nonomiya Alan G. Olivero Emile Plise Jodie Pang Wei Wei Prior Laurent Salphati Lionel Rouge Bing-Yan Zhu 《Bioorganic & medicinal chemistry letters》2010,20(20):6048-6051
Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model. 相似文献
107.
108.
Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G-protein-coupled receptors that modulate adenylyl cyclase and ion channels. Recent research has shown that the CB1 cannabinoid receptor is also coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced by in vitro and in vivo studies. This effect seems to be due to the impact of ceramide on key cell signalling systems such as the extracellular signal-regulated kinase cascade and the Akt pathway. These findings provide a new conceptual view on how cannabinoids act, and raise interesting physiological and therapeutic questions. 相似文献
109.
Cristina López-Gallego 《Biodiversity and Conservation》2008,17(5):1213-1225
Reduced habitat quality after fragmentation can significantly affect population viability, but the effects of differing quality
of the remaining habitat on population fitness are rarely evaluated. Here, I compared fragmented populations of the cycad
Zamia melanorrhachis from habitats with different history and subject to contrasting levels of disturbance to explore potential demographic differences
in populations across habitat patches that could differ in habitat quality. Secondary-forest fragments had a lower canopy
cover and soil moisture than remnant-forest fragments, which may represent a harsh environment for this cycad. A smaller average
plant size and lower population density in the secondary-forest fragments support the hypothesis that these fragments may
be of lower quality, e.g., if plants have reduced survival and/or fecundity in these habitats. However, variation in the stage-structure
of populations (i.e., the relative proportions of non-reproductive and reproductive plants) was associated with the area of
the forest fragments rather than the type of habitat (remnant versus secondary forest). These results suggest that different
demographic parameters may respond differently to habitat fragmentation, which may be explained if processes like adult survival
and recruitment depend on different characteristics of the habitat, e.g., average light/water availability versus suitable
area for plant establishment. This study shows that forest fragments may differ drastically in environmental conditions and
can sustain populations that can vary in their demography. Understanding how forest fragments may represent different habitat
types is relevant for evaluating population viability in a heterogeneous landscape and for designing conservation programs
that account for this heterogeneity. 相似文献
110.
Marco Vinceti Sergio Rovesti Cristina Marchesi Margherita Bergomi Gianfranco Vivoli 《Biological trace element research》1994,40(3):267-275
In a part of the municipal territory of Reggio Emilia, northern Italy, selenium in drinking water decreased from 7 μg/L to
less than 1 μg/L. In a cohort of 4419 individuals, previously exposed for at least 5 yr to the drinking water with higher
selenium content, the 7-yr temporal distribution of deaths for coronary disease and for stroke was analyzed to examine a possible
relationship with changes in drinking water selenium. From January 1986 until August 1988, when tap water selenium was 7 μg/L,
deaths for coronary disease were one in males and two in females. After the decrease in drinking water selenium, 21 and 10
coronary deaths were observed, respectively, in males and in females from September 1988 to December 1992. No significant
difference in the temporal distribution of stroke deaths was observed both in males and in females. Even if an effect of chance
and aging in the temporal distribution of coronary deaths may not be excluded, findings of the study seem to be consistent
with the hypothesis of a beneficial effect of selenium on coronary disease mortality. 相似文献