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1.
Anna Tramontano Elisabetta Bianchi Sara Venturini Franck Martin Antonelo Pessi Maurizio Sallozzo 《Journal of molecular recognition : JMR》1994,7(1):9-24
Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue β-protein aimed at retaining some desirable features of immunogloblin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of main chain conformation of the same regions, based on the ‘canonical structures’ model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical syntyhesis and expression in E. coli and charactgerized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low soubility. We were able to overcome this problem both by further; mutagenesis of the framework and by addition of a solublizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage. 相似文献
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Matthias Albrecht David Kleijn Neal M. Williams Matthias Tschumi Brett R. Blaauw Riccardo Bommarco Alistair J. Campbell Matteo Dainese Francis A. Drummond Martin H. Entling Dominik Ganser G. Arjen de Groot Dave Goulson Heather Grab Hannah Hamilton Felix Herzog Rufus Isaacs Katja Jacot Philippe Jeanneret Mattias Jonsson Eva Knop Claire Kremen Douglas A. Landis Gregory M. Loeb Lorenzo Marini Megan McKerchar Lora Morandin Sonja C. Pfister Simon G. Potts Maj Rundlf Hillary Sardias Amber Sciligo Carsten Thies Teja Tscharntke Eric Venturini Eve Veromann Ines M.G. Vollhardt Felix Wckers Kimiora Ward Andrew Wilby Megan Woltz Steve Wratten Louis Sutter 《Ecology letters》2020,23(10):1488-1498
Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control (18 studies) and pollination services (17 studies) in adjacent crops in North America, Europe and New Zealand. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimise floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future. 相似文献
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Nicola Chiarelli Nicoletta Zoppi Marco Ritelli Marina Venturini Daniele Capitanio Cecilia Gelfi Marina Colombi 《生物化学与生物物理学报:疾病的分子基础》2021,1867(4):166051
Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS nosology. Moreover, the hEDS phenotypic spectrum is wide-ranging and comprises multiple associated signs and symptoms shared with other heritable or acquired connective tissue disorders and chronic inflammatory diseases. In this complex scenario, we previously demonstrated that hEDS patients' skin fibroblasts show phenotypic features of myofibroblasts, widespread extracellular matrix (ECM) disarray, perturbation of ECM-cell contacts, and dysregulated expression of genes involved in connective tissue architecture and related to inflammatory and pain responses. Herein, the cellular proteome of 6 hEDS dermal myofibroblasts was compared to that of 12 control fibroblasts to deepen the knowledge on mechanisms involved in the disease pathogenesis. Qualitative and quantitative differences were assessed based on top-down and bottom-up approaches and some differentially expressed proteins were proofed by biochemical analyses. Proteomics disclosed the differential expression of proteins principally implicated in cytoskeleton organization, energy metabolism and redox balance, proteostasis, and intracellular trafficking. Our findings offer a comprehensive view of dysregulated protein networks and related pathways likely associated with the hEDS pathophysiology. The present results can be regarded as a starting point for future in-depth investigations aimed to decipher the functional impact of potential bioactive molecules for the development of targeted management and therapies. 相似文献
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Francieli Chassot Tarcieli Pozzebon Venturini Fernanda Baldissera Piasentin Janio Morais Santurio Terezinha Inez Estivalet Svidzinski Sydney Hartz Alves 《Revista iberoamericana de micología》2019,36(1):44-47
Background
Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options.Aims
The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2 μg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8 μg/ml), (3) caspofungin-resistant strains (MIC ≥ 8 μg/ml), and (4) micafungin-resistant strains (MIC ≥ 8 μg/ml).Methods
Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done.Results
The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible.Conclusions
Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents. 相似文献9.
Patrick LJM Zeeuwen Jos Boekhorst Ellen H van den Bogaard Heleen D de Koning Peter MC van de Kerkhof Delphine M Saulnier Iris I van Swam Sacha AFT van Hijum Michiel Kleerebezem Joost Schalkwijk Harro M Timmerman 《Genome biology》2012,13(11):R101
Background
Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury.Results
We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes.Conclusions
We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis. 相似文献10.
Josiah MC Heyman 《The journal of the Royal Anthropological Institute》2000,6(4):635-652
High-scale morality is the study of moral ideas and sentiments deployed in relations that encompass multiple, geographically or socially distant populaces. The envisioning of distant people, their attributed moral personhood, the evaluation of their perceived behaviour, and the rectification of wrongs through the use of powerful organizations are key topics in high-scale morality. High-scale morality differs from existing anthropological approaches that emphasize local ethnography or contrastive moral ideas; it addresses the moralization of issues like world hunger, the drug trade, or international migration. The officers of the US Immigration and Naturalization Service understand and evaluate legal and illegal immigrants, as well as directly enacting moral rectification for the US polity. As they resolve moral dilemmas on their job, they utilize pervasive models for moral thought and action in capitalist, individualist, stratified, and bureaucratized societies. The article finishes by considering directions in which anthropology can contribute to understanding the moral dimension of global issues. 相似文献