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161.
Sara Benedetti Pia Bernasconi Enrico Bertini Elena Biagini Giuseppe Boriani Cristina Capanni Nicola Carboni Giovanna Cenacchi Marta Columbaro Monica D’Adamo Adele D’Amico Maria Rosaria D’Apice Marianna Fontana Alessandra Gambineri Giovanna Lattanzi Rocco Liguori Nadir M Maraldi Laura Mazzanti Eugenio Mercuri Tiziana Mongini Lucia O Morandi Iria Neri Giovanni Nigro Giuseppe Novelli Michela Ortolani Renato Pasquali Antonella Pini Stefania Petrini Luisa Politano Stefano Previtali Lisa Pucci Claudio Rapezzi Giulia Ricci Carmelo Rodolico Paolo Sbraccia Emanuela Scarano Gabriele Siciliano Stefano Squarzoni Antonio Toscano Liliana Vercelli Matteo Ziacchi 《Orphanet journal of rare diseases》2012,7(1):1-3
The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy. 相似文献
162.
George B. Stefano Erica Braham Patrick Finn Edward Aiello Michael K. Leung 《Cellular and molecular neurobiology》1987,7(2):209-219
1. This report further demonstrates that etorphine influences presynaptic dopamine release, which in turn centrally modulates peripheral cilioinhibition. 2. In older animals cilioinhibition has become enhanced due to a lack of responsiveness to endogenous opioids which results in greater dopamine release, causing a higher level of cilioinhibition as demonstrated by challenging the visceral ganglia with etorphine or destroying the dopaminergic component with 6-hydroxydopamine. 3. Only the central cilioinhibitory, not the peripheral inhibitory response, mechanism appears to be altered in older animals. Thus, the alteration appears in the central integrative mechanisms involved with regulating ciliary activity. 4. The KCl-stimulated release of dopamine is unaltered in both young and old organisms, whereas the opiate inhibition of the KCl-stimulated release of dopamine is reduced in older organisms. Thus, the aging-associated alteration is associated with a specific process. 5. The reduction of opioid influence and the resulting enhanced cilioinhibitory activity may make the organisms more susceptible to environmental stress. 相似文献
163.
Miriam Kunze Sangsik Jeong Elie Paillard Monika Schönhoff Martin Winter Stefano Passerini 《Liver Transplantation》2011,1(2):274-281
Some cations of ionic liquids (ILs) of interest for high‐energy electrochemical storage devices, such as lithium batteries and supercapacitors, have a structure similar to that of surfactants. For such, it is very important to understand if these IL cations tend to aggregate like surfactants since this would affect the ion mobility and thus the ionic conductivity. The aggregation behaviour of ILs consisting of the bis(trifluoromethanesulfonyl)imide anion and different N‐alkyl‐N‐methyl‐pyrrolidinium cations, with the alkyl chain varied from C3H7 to C8H17, was extensively studied with NMR and Raman methods, also in the presence of Li+ cations. 2H NMR spin‐lattice and spin‐spin relaxation rates were analyzed by applying the “two step” model of surfactant dynamics. Here we show that, indeed, the cations in these ILs tend to form aggregates surrounded by the anions. The effect is even more pronounced in the presence of dissolved lithium cations. 相似文献
164.
Anna M. Mileo Claudia Abbruzzese Stefano Mattarocci Emanuele Bellacchio Paola Pisano Antonio Federico Vittoria Maresca Mauro Picardo Alessandra Giorgi Bruno Maras M. Eugenia Schininà Marco G. Paggi 《PloS one》2009,4(10)
Background
Human Papillomavirus (HPV)-16 is a paradigm for “high-risk” HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation.Methodology/Principal Findings
By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7.Conclusions/Significance
This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells. 相似文献165.
Defining the coast and sentinel ecosystems for coastal observations of global change 总被引:1,自引:0,他引:1
The detection, attribution and prediction of global and large scale regional change are goals for the Global Observing Systems
of the United Nations. Coastal areas are particularly sensitive to global change, but there is a variety of limitations to
universal coverage of observations. The coastal module of the Global Terrestrial Observing System (C-GTOS) considers sentinel
ecosystems to address these goals for the terrestrial, wetland and freshwater ecosystems of the coast. Sentinel ecosystems
for observing systems are a limited number of well understood systems that have substantial datasets and are observed in a
sustained fashion, forming an early warning and core system for broader regional and global change. A necessary step in the
development of C-GTOS is the examination of current definitions of coastal areas by anticipated users and information providers,
and identification of potential coastal networks and sites. We applied the sentinel system framework to the selection of C-GTOS
observation sites from several international programs using various global delineations of coastal areas. Delineations were
based on the most common definitions of the coast adopted by potential C-GTOS users and information providers, and included
mapped areas of various distance from the coastline, coastal areas of low elevation, and a seaward boundary matching the Economic
Exclusive Zone (EEZ). Decreases in the number of sites within each international program occurred with each definition marking
area closer to the coastline. The Ramsar Convention on Wetlands demonstrates the greatest percentage of coastal sites by any
definition. The process of choosing specific sentinel sites for C-GTOS continues from this initial screening, and is the next
step towards the development of an in situ site network supporting the observation of global and large scale change.
An erratum to this article is available at . 相似文献
166.
Volpini R Costanzi S Lambertucci C Vittori S Martini C Trincavelli ML Klotz KN Cristalli G 《Purinergic signalling》2005,1(2):173-181
The synthesis of a series of 9-ethyladenine derivatives bearing alkynyl chains in 2- or 8-position was undertaken, based on the observation that replacement of the sugar moiety in adenosine derivatives with alkyl groups led to adenosine receptor antagonists. All the synthesized compounds were tested for their affinity at human and rat A1, A2A, and A3 adenosine receptors in binding assays; the activity at the human A2B receptor was determined in adenylyl cyclase experiments. Biological data showed that the 2-alkynyl derivatives possess good affinity and are slightly selective for the human A2A receptor. The same compounds tested on the rat A1 and A2A subtypes showed in general lower affinity for both receptors. On the other hand, the affinity of the 8-alkynyl derivatives at the human A1, A2A, and A2B receptors proved to be lower than that of the corresponding 2-alkynyl derivatives. On the contrary, the affinity of the same compounds for the human A3 receptor was improved, resulting in A3 selectivity. As in the case of the 2-alkynyl-substituted compounds, the 8-alkynyl derivatives showed decreased affinity for rat receptors. However, it is worthwhile to note that the 8-phenylethynyl-9-ethyladenine was the most active compound of the two series (Ki in the nanomolar range) at both the human and rat A3 subtype. Docking experiments of the 2- and 8-phenylethynyl-9-ethyladenines, at a rhodopsin-based homology model, gave a rational explanation of the preference of the human A3 receptor for the 8-substituted compound. 相似文献
167.
Frascari D Zannoni A Fedi S Pii Y Zannoni D Pinelli D Nocentini M 《Biodegradation》2005,16(2):147-158
The focus of this microcosm study was to monitor the performances of 17 butane-utilizing microcosms during a long-term (100–250 days) aerobic cometabolic depletion of chloroform (CF). The depletion of the contaminant began after a lag-time variable between 0 and 23 days. All microcosms quickly reached a pseudo steady-state condition, in terms of biomass concentration (with an average of 9.3 × 106 CFU ml–1), chloroform depletion rate (5 mol l–1 d–1) and butane utilization rate (730 mol l–1 d–1). After about 100 days of CF depletion, a sudden 5- to 7-fold increase of the chloroform rate was observed in two microcosms, where the highest amount of contaminant had been depleted. In one of these high-performing microcosms, an experiment of chloroform depletion in the absence of butane resulted in the depletion of a surprisingly high amount of contaminant (765 molCF kgdry soil–1 in 2 months) and in a marked selection of a single bacterial strain. Bioaugmentation assays conducted with the biomass selected in this microcosm and with a pure culture of the selected strain immediately resulted in very high chloroform depletion rates. Preliminary results of a study conducted with resting cells of the selected strain indicated that it can degrade chloroform concentrations up to 119 M (14.2 mg l–1) without any sign of substrate toxicity, and that it is able to transform vinyl chloride and 1,1,2-trichloroethane. 相似文献
168.
Michele Giugliano Giancarlo La Camera Stefano Fusi Walter Senn 《Biological cybernetics》2008,99(4-5):303-318
The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane’s inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite–soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons. 相似文献
169.
Background
Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.Methods
Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO2 and PaCO2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV.Results
Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder.Conclusions
Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated. 相似文献170.
Girotto S Sturlese M Bellanda M Tessari I Cappellini R Bisaglia M Bubacco L Mammi S 《The Journal of biological chemistry》2012,287(22):18738-18749
The physiological role of DJ-1, a protein involved in familial Parkinson disease is still controversial. One of the hypotheses proposed indicates a sensor role for oxidative stress, through oxidation of a conserved cysteine residue (Cys-106). The association of DJ-1 mutations with Parkinson disease suggests a loss of function, specific to dopaminergic neurons. Under oxidative conditions, highly reactive dopamine quinones (DAQs) can be produced, which can modify cysteine residues. In cellular models, DJ-1 was found covalently modified by dopamine. We analyzed the structural modifications induced on human DJ-1 by DAQs in vitro. We described the structural perturbations induced by DAQ adduct formation on each of the three cysteine residues of DJ-1 using specific mutants. Cys-53 is the most reactive residue and forms a covalent dimer also in SH-SY5Y DJ-1-transfected cells, but modification of Cys-106 induces the most severe structural perturbations; Cys-46 is not reactive. The relevance of these covalent modifications to the several functions ascribed to DJ-1 is discussed in the context of the cell response to a dopamine-derived oxidative insult. 相似文献