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41.
D-amino acid oxidase (DAAO) is a flavoprotein that catalyzes stereospecifically the oxidative deamination of D-amino acids. The wild-type DAAO is mainly active on neutral D-amino acids, while basic D-amino acids are poor substrates and the acidic ones are virtually not oxidized. To present a comprehensive picture of how the active site residues can modulate the substrate specificity a number of mutants at position M213, Y223, Y238, R285, S335, and Q339 were prepared in the enzyme from the yeast Rhodotorula gracilis. All DAAO mutants have spectral properties similar to those of the wild-type enzyme and are catalytically active, thus excluding an essential role in catalysis; a lower activity on neutral and basic amino acids was observed. Interestingly, an increase in activity and (k(cat)/K(m))(app) ratio on D-aspartate was observed for all the mutants containing an additional charged residue in the active site. The active site of yeast DAAO appears to be a highly evolved scaffold built up through evolution to optimize the oxidative deamination of neutral D-amino acids without limiting its substrate specificity. It is noteworthy, that introduction of a sole, additional, positively charged residue in the active site is sufficient to optimize the reactivity on acidic D-amino acids, giving rise to kinetic properties similar to those of D-aspartate oxidase. 相似文献
42.
Perinotto WM Angelo IC Golo PS Quinelato S Camargo MG Sá FA Bittencourt VR 《Experimental parasitology》2012,130(3):257-260
This study aimed to evaluate the in vitro effect of the entomopathogenic fungi Metarhizium anisopliae sensu lato (s.l.) and Beauveria bassiana sensu lato (s.l.) on two distinct populations of Rhipicephalus microplus, from two different experimental farms. Bioassays were performed with engorged females, eggs and larvae. Fungal infection was evaluated based on biological parameters of treated engorged females, percentage of hatch from treated eggs, and percentage of mortality and mean lethal time (LT90) of treated larvae. When the treatments were compared between the two populations, there were significant differences in the following parameters: pre-oviposition period, hatching period and egg production index. Moreover, the results showed that B. bassiana s.l., isolate Bb 986, was more virulent than M. anisopliae s.l., isolate 959, for engorged females, showing a control percentage of 49%. In the bioassay with eggs, the hatching percentage ranged from 3.1% to 49.5% in one population and from 3.4% to 42.7% in the other, with no significant difference between the two populations. In the bioassay with unfed larvae, the mortality percentage ranged from 91.8% to 98.7% in one population and from 71.0% to 94.0% in the other. The LT(90) varied from 19.52 to 27.51 days in one of the populations and 22.89 to 37.31 days in the other. These results suggest that populations of R. microplus show distinct variation in their susceptibility to B. bassiana s.l. and M. anisopliae s.l. 相似文献
43.
Rachael A. Murtaugh Angelo P. Capparella John C. Kostelnick Greg D. Johnson 《The Journal of wildlife management》2019,83(6):1345-1351
Bat fatality at wind energy facilities is a conservation issue, but its effect on bat populations is difficult to estimate. We have little understanding of wind turbine effects on bat population persistence, in part because we have poor knowledge of bat migration pathways and hence the source populations for individual fatalities. We used deuterium ratio analysis combined with genetic algorithm for rule-set prediction and the web-based isoscapes modeling, analysis, and prediction in a geographic information system environment as a novel approach. Our objectives were to explore the utility of these methods together and map the geographic extents of eastern red bat (Lasiurus borealis) specimens salvaged in 2008–2010 from a single, 92-km2 wind energy facility in Illinois, USA. Results indicate that combining these methods can be successful and support their use with species where ranges may be less well defined. Because of the migratory nature of this species and the range of deuterium values of pixels in our isotope model, we predicted that 18% and 82% of the specimens would have isotope results inside and outside of the wind facility's isocline respectively. We concluded that 71.4% of the specimens had isotope signatures placing them outside the wind facility's isocline. It could be argued that the wide distribution of bat fatalities dilutes the overall effect of those fatalities on the bat species; however, if other facilities show a similar pattern, each facility could have cumulative and far reaching population-level effects. © 2019 The Wildlife Society. 相似文献
44.
The NHERF1 PDZ2 domain regulates PKA-RhoA-p38-mediated NHE1 activation and invasion in breast tumor cells 总被引:1,自引:0,他引:1
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Cardone RA Bellizzi A Busco G Weinman EJ Dell'Aquila ME Casavola V Azzariti A Mangia A Paradiso A Reshkin SJ 《Molecular biology of the cell》2007,18(5):1768-1780
Understanding the signal transduction systems governing invasion is fundamental for the design of therapeutic strategies against metastasis. Na(+)/H(+) exchanger regulatory factor (NHERF1) is a postsynaptic density 95/disc-large/zona occludens (PDZ) domain-containing protein that recruits membrane receptors/transporters and cytoplasmic signaling proteins into functional complexes. NHERF1 expression is altered in breast cancer, but its effective role in mammary carcinogenesis remains undefined. We report here that NHERF1 overexpression in human breast tumor biopsies is associated with metastatic progression, poor prognosis, and hypoxia-inducible factor-1alpha expression. In cultured tumor cells, hypoxia and serum deprivation increase NHERF1 expression, promote the formation of leading-edge pseudopodia, and redistribute NHERF1 to these pseudopodia. This pseudopodial localization of NHERF1 was verified in breast biopsies and in three-dimensional Matrigel culture. Furthermore, serum deprivation and hypoxia stimulate the Na(+)/H(+) exchanger, invasion, and activate a protein kinase A (PKA)-gated RhoA/p38 invasion signal module. Significantly, NHERF1 overexpression was sufficient to induce these morphological and functional changes, and it potentiated their induction by serum deprivation. Functional experiments with truncated and binding groove-mutated PDZ domain constructs demonstrated that NHERF1 regulates these processes through its PDZ2 domain. We conclude that NHERF1 overexpression enhances the invasive phenotype in breast cancer cells, both alone and in synergy with exposure to the tumor microenvironment, via the coordination of PKA-gated RhoA/p38 signaling. 相似文献
45.
Daniela Minerdi Simone Bossi Maria Lodovica Gullino Angelo Garibaldi 《Environmental microbiology》2009,11(4):844-854
Fusarium oxysporum MSA 35 [wild-type (WT) strain] is an antagonistic Fusarium that lives in association with a consortium of bacteria belonging to the genera Serratia, Achromobacter , Bacillus and Stenotrophomonas in an Italian soil suppressive to Fusarium wilt. Typing experiments and virulence tests provided evidence that the F. oxysporum isolate when cured of the bacterial symbionts [the cured (CU) form], is pathogenic, causing wilt symptoms identical to those caused by F. oxysporum f. sp. lactucae . Here, we demonstrate that small volatile organic compounds (VOCs) emitted from the WT strain negatively influence the mycelial growth of different formae speciales of F. oxysporum. Furthermore, these VOCs repress gene expression of two putative virulence genes in F. oxysporum lactucae strain Fuslat10, a fungus against which the WT strain MSA 35 has antagonistic activity. The VOC profile of the WT and CU fungus shows different compositions. Sesquiterpenes, mainly caryophyllene, were present in the headspace only of WT MSA 35. No sesquiterpenes were found in the volatiles of ectosymbiotic Serratia sp. strain DM1 and Achromobacte r sp. strain MM1. Bacterial volatiles had no effects on the growth of the different ff. spp. of F. oxysporum examined. Hyphae grown with VOC from WT F. oxysporum f. sp. lactucae strain MSA 35 were hydrophobic whereas those grown without VOCs were not, suggesting a correlation between the presence of volatiles in the atmosphere and the phenotype of the mycelium. This is the first report of VOC production by antagonistic F. oxysporum MSA 35 and their effects on pathogenic F. oxysporum. The results obtained in this work led us to propose a new potential direct long-distance mechanism for antagonism by F. oxysporum MSA 35 mediated by VOCs . Antagonism could be the consequence of both reduction of pathogen mycelial growth and inhibition of pathogen virulence gene expression. 相似文献
46.
Recchia-Luciani AN 《Biosemiotics》2012,5(1):95-120
The present paper proposes a definition for the complex polysemic concepts of consciousness and awareness (in humans as well
as in other species), and puts forward the idea of a progressive ontological development of consciousness from a state of
‘childhood’ awareness, in order to explain that humans are not only able to manipulate objects, but also their mental representations.
The paper builds on the idea of qualia intended as entities posing regular invariant requests to neural processes, trough
the permanence of different properties. The concept of semantic differential introduces the properties of metaphorical qualia as an exclusively human ability. Furthermore this paper proposes a classification of qualia, according to the models–with
different levels of abstraction–they are implied in, in a taxonomic perspective. This, in turn, becomes a source of categorization
of divergent representations, sign systems, and forms of intentionality, relying always on biological criteria. New emerging
image-of-the-world-devices are proposed, whose qualia are likely to be only accessible to humans: emotional qualia, where emotion accounts for the invariant and dominant property; and the qualic self where continuity, combined with the oneness of the self, accounts for the invariant and dominant property. The concept of
congruence between different domains in a metaphor introduces the possibility of a general evaluation of truth and falsity
of all kinds of metaphorical constructs, while the work of Matte Blanco enables us to classify conscious versus unconscious
metaphors, both in individuals and in social organizations. 相似文献
47.
Abstract Two Dematiaceous Hyphomycetes, Beltraniella lyrata and Beltraniopsis fabularis, found on tropical forest litter in the Tai National Park in Ivory Coast are proposed as new species and described. 相似文献
48.
Irene Faravelli Megi Meneri Domenica Saccomanno Daniele Velardo Elena Abati Delia Gagliardi Valeria Parente Lucia Petrozzi Dario Ronchi Nino Stocchetti Edoardo Calderini Grazia D’Angelo Giovanna Chidini Edi Prandi Giulia Ricci Gabriele Siciliano Nereo Bresolin Giacomo Pietro Comi Stefania Corti Francesca Magri Alessandra Govoni 《Journal of cellular and molecular medicine》2020,24(5):3034-3039
The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response. 相似文献
49.
Giovanna Carr Paolo Nicoli Marcello Francesco Lingua Beatrice Maffeo Antonio Cartell Paola Circosta Mara Brancaccio Guido Parvis Valentina Gaidano Angelo Guerrasio Giuseppe Saglio Riccardo Taulli Alessandro Morotti 《Journal of cellular and molecular medicine》2020,24(2):1650-1657
The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19+ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones. 相似文献
50.
Angelo Toto Sana Ma Francesca Malagrin Lorenzo Visconti Livia Pagano Kristian Stromgaard Stefano Gianni 《Protein science : a publication of the Protein Society》2020,29(10):2038-2042
The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS‐CoV and SARS‐CoV‐2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ‐binding motif at its C‐terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS‐CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS‐CoV and SARS‐CoV‐2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS‐CoV‐2 compared to SARS‐CoV may rely on the increased affinity of its Envelope protein for PALS1. 相似文献