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121.
Ivana Malvacio Alberto Cuzzolin Mattia Sturlese D. Mariano A. Vera 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):171-183
The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2?H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e2 and 4h2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories. 相似文献
122.
Mice with reduced expression of the telomere‐associated protein Ft1 develop p53‐sensitive progeroid traits 下载免费PDF全文
Mattia La Torre Chiara Merigliano Romina Burla Carla Mottini Giorgia Zanetti Simona Del Giudice Mariateresa Carcuro Ilaria Virdia Elisabetta Bucciarelli Isabella Manni Gianluca Rampioni Vinciguerra Giulia Piaggio Mara Riminucci Ana Cumano Armando Bartolazzi Fiammetta Vernì Silvia Soddu Maurizio Gatti Isabella Saggio 《Aging cell》2018,17(4)
Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved in telomere maintenance and DNA replication. AKTIP also interacts with A‐ and B‐type lamins. These features suggest that Ft1 may be implicated in aging regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant (Ft1kof/kof) mice exhibit telomeric defects and that Ft1kof/kof animals develop progeroid traits, including impaired growth, skeletal and skin defects, abnormal heart tissue, and sterility. We also demonstrate a genetic interaction between Ft1 and p53. The analysis of mice carrying mutations in both Ft1 and p53 (Ft1kof/kof; p53ko/ko and Ft1kof/kof; p53+/ko) showed that reduction in p53 rescues the progeroid traits of Ft1 mutants, suggesting that they are at least in part caused by a p53‐dependent DNA damage response. Conversely, Ft1 reduction alters lymphomagenesis in p53 mutant mice. These results identify Ft1 as a new player in the aging process and open the way to the analysis of its interactions with other progeria genes using the mouse model. 相似文献
123.
Nadia Starc Min Li Mattia Algeri Antonella Conforti Luigi Tomao Angela Pitisci Francesco Emma Giovanni Montini Piergiorgio Messa Franco Locatelli Maria Ester Bernardo Marina Vivarelli 《Cytotherapy》2018,20(3):322-334
Background
Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases in the pediatric population; considering the role of the immune system in its pathogenesis, corticosteroids are used as first-line immunosuppressive treatment. Due to its chronic nature and tendency to relapse, a significant proportion of children experience co-morbidity due to prolonged exposure to corticosteroids and concomitant immunosuppression with second-line, steroid-sparing agents. Mesenchymal stromal cells (MSCs) are multipotent cells that represent a key component of the bone marrow (BM) microenvironment; given their unique immunoregulatory properties, their clinical use may be exploited as an alternative therapeutic approach in INS treatment.Methods
In view of the possibility of exploiting their immunoregulatory properties, we performed a phenotypical and functional characterization of MSCs isolated from BM of five INS patients (INS-MSCs; median age, 13 years; range, 11–16 years) in comparison with MSCs isolated from eight healthy donors (HD-MSCs). MSCs were expanded ex vivo and then analyzed for their properties.Results
Morphology, proliferative capacity, immunophenotype and differentiation potential did not differ between INS-MSCs and HD-MSCs. In an allogeneic setting, INS-MSCs were able to prevent both T- and B-cell proliferation and plasma-cell differentiation. In an in-vitro model of experimental damage to podocytes, co-culture with INS-MSCs appeared to be protective.Discussion
Our results demonstrate that INS-MSCs maintain the main biological and functional properties typical of HD-MSCs; these data suggest that MSCs may be used in autologous cellular therapy approaches for INS treatment. 相似文献124.
Mauro Gobbi Álvaro Barragán Mattia Brambilla Emilia Moreno Washington Pruna Pierre Moret 《Journal of Insect Conservation》2018,22(3-4):533-543
The use of ground beetles (Coleoptera: Carabidae) as bioindicators of environmental change depends on the reliability and the effectiveness of the sampling methods. Those that have been tested in the temperate zone and in tropical forests still await experimentation in tropical high-altitude environments. For the first time, pitfall trapping and hand searching have been compared in Ecuadorian páramo above 4000 m a.s.l., in terms of practical effectiveness. The study was performed on six volcanoes and was based on the comparison of 28 sampling sessions (pitfall trapping and hand searching) performed along two different elevational belts [lower superpáramo (LSP) and upper superpáramo (USP)]. Analyses of sampling sessions showed that detected species richness is slightly higher with hand searching than with pitfall trapping, regardless of the elevation. Additionally, hand searching is more time-effective than pitfall trapping. The performance of the sampling method slightly varies when species assemblage composition is analysed in relation to elevational belts. In the LSP, hand searching and pitfall trapping should be simultaneously used to obtain exhaustive inventories of carabid biodiversity, since different species are likely to be collected by each method. In the USP, hand searching and pitfall trapping efficiency is very similar, but hand searching allows to collect a slightly larger number of species. Lastly, the sample-based rarefaction curves showed that four temporal replicates are mandatory to obtain a robust dataset and an exhaustive inventory of the true species richness and species assemblages composition. Our findings suggest a combined use of hand searching and pitfall trapping in the LSP, while both methods can be used alone for surveying carabids in the USP. Furthermore, hand searching is recommended if the aim is to obtain an inventory of species diversity, whereas pitfall trapping seems more convenient for fine grain ecological and comparative studies. 相似文献
125.
Dongliang Du Xiaoyun Du Matthew R. Mattia Yanbo Wang Qibin Yu Ming Huang Yuan Yu Jude W. Grosser Fred G. GmitterJr 《Tree Genetics & Genomes》2018,14(4):43
Long terminal repeat retrotransposons (LTR-RTs) are a large portion of most plant genomes, and can be used as a powerful molecular marker system. The first citrus reference genome (Citrus x clementina) has been publicly available since 2011; however, previous studies in citrus have not utilized the whole genome for LTR-RT marker development. In this study, 3959 full-length LTR-RTs were identified in the C. x clementina genome using structure-based (LTR_FINDER) and homology-based (RepeatMasker) methods. LTR-RTs were first classified by protein domain into Gypsy and Copia superfamilies, and then clustered into 1074 families based on LTR sequence similarity. Three hundred fifty Copia families were grouped into four lineages: Retrofit, Tork, Sire, and Oryco. One hundred seventy-eight Gypsy families were sorted into six lineages: Athila, Tat, Renia, CRM, Galadriel, and Del. Most LTR-RTs (3218 or 81.3%) were anchored to the nine Clementine mandarin linkage groups, accounting for 9.74% of chromosomes currently assembled. Accessions of 25 Rutaceae species were genotyped using 17 inter-retrotransposon amplified polymorphism (IRAP) markers developed from conserved LTR regions. Sequence-specific amplified polymorphism (SSAP) makers were used to distinguish ‘Valencia’ and ‘Pineapple’ sweet oranges (C. x sinensis), and 24 sweet orange clones. LTR-RT markers developed from the Clementine genome can be transferred within the Rutaceae family demonstrating that they are an excellent tool for citrus and Rutaceae genetic analysis. 相似文献
126.
A review and meta‐analysis of the effects of climate change on Holarctic mountain and upland bird populations 下载免费PDF全文
Davide Scridel Mattia Brambilla Kathy Martin Aleksi Lehikoinen Aaron Iemma Anderle Matteo Susanne Jähnig Enrico Caprio Giuseppe Bogliani Paolo Pedrini Antonio Rolando Raphaël Arlettaz Dan Chamberlain 《Ibis》2018,160(3):489-515
Mountain regions are globally important areas for biodiversity but are subject to multiple human‐induced threats, including climate change, which has been more severe at higher elevations. We reviewed evidence for impacts of climate change on Holarctic mountain bird populations in terms of physiology, phenology, trophic interactions, demography and observed and projected distribution shifts, including effects of other factors that interact with climate change. We developed an objective classification of high‐elevation, mountain specialist and generalist species, based on the proportion of their breeding range occurring in mountain regions. Our review found evidence of responses of mountain bird populations to climate (extreme weather events, temperature, rainfall and snow) and environmental (i.e. land use) change, but we know little about either the underlying mechanisms or the synergistic effects of climate and land use. Long‐term studies assessing reproductive success or survival of mountain birds in relation to climate change were rare. Few studies have considered shifts in elevational distribution over time and a meta‐analysis did not find a consistent direction in elevation change. A meta‐analysis carried out on future projections of distribution shifts suggested that birds whose breeding distributions are largely restricted to mountains are likely to be more negatively impacted than other species. Adaptation responses to climate change rely mostly on managing and extending current protected areas for both species already present, and for expected colonizing species that are losing habitat and climate space at lower elevation. However, developing effective management actions requires an improvement in the current knowledge of mountain species ecology, in the quality of climate data and in understanding the role of interacting factors. Furthermore, the evidence was mostly based on widespread species rather than mountain specialists. Scientists should provide valuable tools to assess the status of mountain birds, for example through the development of a mountain bird population index, and policy‐makers should influence legislation to develop efficient agri‐environment schemes and forestry practices for mountain birds, as well as to regulate leisure activities at higher elevations. 相似文献
127.
128.
Mattia Damiani Montserrat Núñez Philippe Roux Eléonore Loiseau Ralph K. Rosenbaum 《The International Journal of Life Cycle Assessment》2018,23(10):2071-2088
Purpose
In recent history, human development overbalanced towards economic growth has often been accompanied by the degradation and reduction of freshwater resources at the expense of freshwater dependent ecosystems. For their subsistence and correct functioning, understanding environmental water requirements (EWR) represents an area of great interest for life cycle impact assessment (LCIA) and it has been only marginally explored. The aim of this paper is to investigate how this concept has evolved in ecological and hydrological literature and how it can be better integrated in LCIA, to identify potential options for improvement of LCIA indicators in the short, mid and long term.Methods
To address the limitations of existing LCIA approaches in modelling EWR, four families of EWR methods have been reviewed, namely hydrological, hydraulic, habitat simulation and holistic methods. Based on existing scientific literature and their broad application, 24 methods have been selected and their suitability to be adopted in LCIA has been evaluated against nine criteria, with regard to data management issues, accuracy, scientific robustness, and potential for future development. A semi-quantitative performance score has been subsequently assigned for each criterion, showing the main strengths and weaknesses of selected methods.Results and discussion
The underlying rationale of the chosen approaches is markedly different, likewise the input information needed and results applicability. Hydrological methods are well suited for the development of global models and they are the only ones currently considered in LCIA, although their applicability remains limited to water stress indicators. Habitat modelling is identified as an essential step for the development of mechanistic LCIA models and endpoint indicators. In this respect, hydraulic, habitat simulation and holistic methods are fit for the purpose. However, habitat simulation methods represent the best compromise between scientific robustness and applicability in LCIA. For this reason, a conceptual framework for the development of habitat-based characterization factors has been proposed. Among the evaluated habitat simulation methods, ESTIMHAB showed the best performance and was the method retained for the development of an LCIA model that will assess the consequences of water consumption on stream ecosystems.Conclusions
This study identifies the advantages of specific modelling approaches for the assessment of water requirements for ecosystems. Selected methods could support the development of LCIA models at different levels. In the short-term for improving environmental relevance of water stress indicators, and in the mid/long-term to build up midpoint habitat indicators relating water needs of ecosystems with new endpoint metrics.129.
Mattia Mori Davide Deodato Mohan Kasula Davide M. Ferraris Adriana Sanna Alessandro De Logu Menico Rizzi Maurizio Botta 《Bioorganic & medicinal chemistry letters》2018,28(4):637-641
Sixteen 3-(carboxymethyl)rhodanines, and twelve aminothiazoles as rhodanine-mimetics were designed, synthesized and tested as inhibitors of the Zmp1 enzyme from Mycobacterium tuberculosis (Mtb). Almost all rhodanines (5a–d, 5f–n, and 7a–b) exhibited Zmp1 inhibition with IC50 values in the range 1.3–43.9?µM, whereas only aminothiazoles 12b and 12d proved active with IC50 values of 41.3 and 35.7?µM, respectively. Structure-activity relationships (SAR) were coupled with molecular modeling studies to highlight structural determinants for Zmp1 inhibition. Moreover, rhodanines 5a and 5c induced 23.4 and 53.8% of Mtb growth inhibition in THP-1 infected cells, respectively, at the non-toxic concentration of 10?µg/ml. This work represents a step forward in targeting Zmp1 by small molecules. 相似文献
130.
S. Filosa N. Giacometti C. Wangwei D. De Mattia D. Pagnini F. Alfinito F. Schettini L. Luzzatto G. Martini 《American journal of human genetics》1996,59(4):887-895
X-chromosome inactivation in mammals is regarded as an essentially random process, but the resulting somatic-cell mosaicism creates the opportunity for cell selection. In most people with red-blood-cell glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme-deficient phenotype is only moderately expressed in nucleated cells. However, in a small subset of hemizygous males who suffer from chronic nonspherocytic hemolytic anemia, the underlying mutations (designated class I) cause more-severe G6PD deficiency, and this might provide an opportunity for selection in heterozygous females during development. In order to test this possibility we have analyzed four heterozygotes for class I G6PD mutations: two with G6PD Portici (1178G-->A) and two with G6PD Bari (1187C-->T). We found that in fractionated blood cell types (including erythroid, myeloid, and lymphoid cell lineages) there was a significant excess of G6PD-normal cells. The significant concordance that we have observed in the degree of imbalance in the different blood-cell lineages indicates that a selective mechanism is likely to operate at the level of pluripotent blood stem cells. Thus, it appears that severe G6PD deficiency affects adversely the proliferation or the survival of nucleated blood cells and that this phenotypic characteristic is critical during hematopoiesis. 相似文献