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791.
A Achilli L Iommarini A Olivieri M Pala B Hooshiar Kashani P Reynier C La Morgia ML Valentino R Liguori F Pizza P Barboni F Sadun AM De Negri M Zeviani H Dollfus A Moulignier G Ducos C Orssaud D Bonneau V Procaccio B Leo-Kottler S Fauser B Wissinger P Amati-Bonneau A Torroni V Carelli 《PloS one》2012,7(8):e42242
Background
Leber’s hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes). However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined.Methodology/Principal Findings
In order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M), MT-ND4L (m.10663T>C/p.V65A) and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S). Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I.Conclusions/Significance
Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe) and other putative synergistic mtDNA variants in LHON expression. 相似文献792.
Berardi R Santinelli A Onofri A Brunelli A Pierantoni C Pisa E Pagliacci A Stramazzotti D Zuccatosta L Mazzanti P Sabbatini A Gasparini S Bearzi I Cascinu S 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2012,34(2):72-78
793.
Manuel Hidalgo Tristan Rouyer Valerio Bartolino Santiago Cerviño Lorenzo Ciannelli Enric Massutí Angelique Jadaud Fran Saborido‐Rey Joël M. Durant Marina Santurtún Carmen Piñeiro Nils C. Stenseth 《Ecography》2012,35(7):637-649
Fisheries ecologists traditionally aimed at disentangling climate and fishing effects from the population dynamics of exploited marine fish stocks. However, recent studies have shown that internal characteristics and external forcing (climate and exploitation) have interactive rather than additive effects. Thought most of these studies explored how demographic truncation induced by exploitation affected the response of recruitment to climate, identifying a general pattern revealed to be difficult as interactions are often case‐specific. Here we compared five exploited stocks of European hake Merluccius merluccius from the Atlantic Ocean and Mediterranean Sea to investigate how the interaction between internal characteristics and external forces affect the variability of the population growth rate and their consequences on recruitment. Our results show that demographic truncation induces a novel population scenario in which the growth rate is maximized when the reproductive stock is younger and less diverse. This scenario is shaped by the climate variability and the fishing pattern. The population growth rate becomes more dependent on the maturation schedule and less on the survival rates. The consequences for the recruitment dynamics are twofold; the effect of density‐dependent regulatory processes decreases while the effect of the density‐independent drivers increases. Our study shows that the interaction between internal characteristics and external forces changes across geographic locations according to 1) the importance of demographic truncation, 2) the influence of the climate on the regional hydrography and 3) the spatiotemporal heterogeneity of the physical environment to which fish life history is adapted. 相似文献
794.
De Donato M Mariani M Petrella L Martinelli E Zannoni GF Vellone V Ferrandina G Shahabi S Scambia G Ferlini C 《Journal of cellular physiology》2012,227(3):1034-1041
The Class III β-tubulin isotype (βIII-tubulin) is a predictive biomarker in ovarian cancer and other solid tumor malignancies. We discovered that βIII-tubulin function is linked to two GTPases: guanylate-binding protein 1 (GBP1), which activates its function, and GNAI1, which inhibits it. This finding was demonstrated in a panel of ovarian cancer cells resistant to several chemotherapeutic agents. Using a protein microarray, we identified PIM1 as the downstream partner of GBP1, recruited into the cytoskeleton under hypoxic conditions. The clinical value of these observations was tested by performing an archive study of 98 ovarian cancer patients, which demonstrated that the βIII-tubulin -/PIM1- cohort responded to treatment, exhibiting long overall survival (OS), while βIII-tubulin +/PIM+ patients experienced poor outcomes and OS times similar to patients receiving palliation alone. βIII-tubulin expression is commonly believed responsible for paclitaxel resistance due to its enhancement of the dynamic instability of microtubules, which counteracts the activity of taxanes. In contrast, our research reveals that βIII-tubulin behaves as a gateway for prosurvival signals, such as PIM1, to move into the cytoskeleton. When cells are exposed to microenvironmental stressors, they activate this pathway by telling the cytoskeleton to incorporate PIM1 through GBP1 and βIII-tubulin, which ultimately leads to drug resistance. This discovery reveals that βIII-tubulin does not act alone but requires partners to play its role. The discovery of such protein:protein interactions underlying this prosurvival cascade makes feasible the development of therapeutic approaches using novel compounds that are capable of inhibiting the transmission of prosurvival signals into the cytoskeleton. 相似文献
795.
Leopaldi AM Vismara R Lemma M Valerio L Cervo M Mangini A Contino M Redaelli A Antona C Fiore GB 《Journal of biomechanics》2012,45(7):1133-1139
Due to their high complexity, surgical approaches to valve repair may benefit from the use of in vitro simulators both for training and for the investigation of those measures which can lead to better clinical results. In vitro tests are intrinsically more effective when all the anatomical substructures of the valvular complexes are preserved. In this work, a mock apparatus able to house an entire explanted porcine heart and subject it to pulsatile fluid-dynamic conditions was developed, in order to enable the hemodynamic analysis of simulated surgical procedures and the imaging of the valvular structures. The mock loop's hydrodynamic design was based on an ad-hoc defined lumped-parameter model. The left ventricle of an entire swine heart was dynamically pressurized by an external computer-controlled pulse duplicator. The ascending aorta was connected to a hydraulic circuit which simulated the input impedance of the systemic circulation; a reservoir passively filled the left atrium. Accesses for endoscopic imaging were located in the apex of the left ventricle and in the aortic root. The experimental pressure and flow tracings were comparable with the typical in vivo curves; a mean flow of 3.5±0.1l pm and a mean arterial pressure of 101±2 mmHg was obtained. High-quality echographic and endoscopic video recordings demonstrated the system's excellent potential in the observation of the cardiac structures dynamics. The proposed mock loop represents a suitable in vitro system for the testing of minimally-invasive cardiovascular devices and surgical procedures for heart valve repair. 相似文献
796.
This article deals with the safety assessment of several ultra-wideband (UWB) antenna designs for use in prototype microwave breast imaging systems. First, the performances of the antennas are validated by comparison of measured and simulated data collected for a simple test case. An efficient approach to estimating the specific energy absorption (SA) is introduced and validated. Next, SA produced by the UWB antennas inside more realistic breast models is computed. In particular, the power levels and pulse repetition periods adopted for the SA evaluation follow the measurement protocol employed by a tissue sensing adaptive radar (TSAR) prototype system. Results indicate that the SA for the antennas examined is below limits prescribed in standards for exposure of the general population; however, the difficulties inherent in applying such standards to UWB exposures are discussed. The results also suggest that effective tools for the rapid evaluation of new sensors have been developed. 相似文献
797.
Mammoli V Bonifazi A Del Bello F Diamanti E Giannella M Hudson AL Mattioli L Perfumi M Piergentili A Quaglia W Titomanlio F Pigini M 《Bioorganic & medicinal chemistry》2012,20(7):2259-2265
Aim of the present study was to obtain novel α(2)-adrenoreceptor (α(2)-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective α(2)-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole α(2A)-subtype. Moreover, 2 showed an affinity at I(2)-imidazoline binding sites (I(2)-IBS) comparable to that at α(2A)-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of α(2A)-AR antagonism in the I(2)-IBS-mediated morphine analgesia enhancement. 相似文献
798.
Stura E Bruzzese D Valerio F Grasso V Perlo P Nicolini C 《Biosensors & bioelectronics》2007,23(5):655-660
In this work, to improve the mechanical stability of electrodes based on P450scc for LDL-cholesterol detection and measure, anodic porous alumina (APA) was used. This inorganic matrix, which pores can be tuned in diameter modifying the synthesis parameters, was realized with cavities 275 nm wide and 160 microm deep (as demonstrated with AFM and SEM measurement), to allow the immobilization of P450scc macromolecules preserving their electronic sensitivity to its native substrate, cholesterol. Even if the sensitivity of the APA+P450scc system was slightly reduced with respect to the pure P450scc system, the readout was stable for a much longer period of time, and the measures remained reproducible inside a proper confidentiality band, as demonstrated with several cyclic voltammetry measures. To optimize the adhesion of P450scc to APA, a layer of poly-L-lysine, a poly-cathion, was successfully implemented as intermediate organic structure. 相似文献
799.
Design,Synthesis, Lipophilic Properties,and Binding Affinities of Potential Ligands in Positron Emission Tomography (PET) for Visualization of Brain Dopamine D4 Receptors 下载免费PDF全文
Enza Lacivita Paola De Giorgio Nicola A. Colabufo Francesco Berardi Roberto Perrone Mauro Niso Marcello Leopoldo 《化学与生物多样性》2014,11(2):299-310
We report the synthesis of compounds structurally related to the high‐affinity dopamine D4 receptor ligand N‐{2‐[4‐(3‐cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐methoxybenzamide ( 1e ). All compounds were specifically designed as potential PET radioligands for brain D4 receptor visualization, having lipophilicity within a range for brain uptake and weak non‐specific binding (0.75<cLogP<3.15) and bearing a substituent for easy access to labeling with the positron emitter isotope 11C or 18F. The best compound of the series, N‐{2‐[4‐(4‐chlorophenyl)piperazin‐1‐yl]ethyl}‐6‐fluoropyridine‐3‐carboxamide ( 7a ), displayed excellent selectivity over D2 and D3 receptors (>100‐fold), but its D4 receptor affinity was suboptimal for imaging of brain D4 receptors (Ki=30 nM ). 相似文献
800.