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91.
Bettina Maccagnani Francesca Giacomello Marco Fanti Davide Gobbin Stefano Maini Gino Angeli 《BioControl》2009,54(1):123-133
The efficiency of two pollinators, Apis mellifera L. (Hymenoptera: Apidae) and the mason bee Osmia cornuta (Latreille) (Hymenoptera: Megachilidae), as carriers of biocontrol agents (BCA) from flower to flower (secondary colonisation) was investigated on apple cv ‘Golden Delicious’. The BCA tested was Bacillus subtilis, strain BD170 (Biopro®) developed for the control of the ‘fire blight’ caused by Erwinia amylovora (Burril) Winslow et al. The two insect species were studied as secondary BCA carriers on apple plants in pots under net screened tunnels. Their behaviour and capacity to deposit the BCA in the most receptive flower parts were compared both by washing, diluting and plating the flower organs on a recovery medium and by means of PCR analyses based on a molecular marker. O. cornuta showed better performances with respect to A. mellifera. For the field trials, pollinators were introduced in four apple orchards. During apple’s flowering, the BD170 (100 g hl?l) was sprayed once in two fields, and twice in the others. The pollinators’ efficacy in carrying the BCA from sprayed flowers to the stigmas of newly opened ones at different times after the spray treatment was evaluated. The detection of the BCA was performed by PCR analysis. The percentages of positive PCR flower samples were higher in the internal treated areas of the fields with respect to the external untreated ones, but the high colonisation level found in the latter and in the flowers opened in both areas several days after the treatment(s) demonstrated that pollinators can play an important role as secondary carriers. 相似文献
92.
Strappaghetti G Brodi C Giannaccini G Betti L 《Bioorganic & medicinal chemistry letters》2006,16(10):2575-2579
Continuing our research aimed at obtaining new compounds with high affinity and selectivity toward alpha(1)-AR, a new series of arylpiperazine derivatives was designed, synthesized, and biologically tested. The new compounds 1-17 are characterized by a phenylphthalazin-1(2H)-one fragment connected through an alkyl chain to an arylpiperazine residue. The pharmacological profile of these compounds was evaluated for their affinity and selectivity toward alpha(1)-AR, alpha(2)-AR and toward 5HT(1A) serotoninergic receptor. A discussion on the structure-activity relationship (SAR) of these compounds is also reported. 相似文献
93.
Ghidini E Delcanale M De Fanti R Rizzi A Mazzuferi M Rodi D Simonato M Lipreri M Bassani F Battipaglia L Bergamaschi M Villetti G 《Bioorganic & medicinal chemistry》2006,14(10):3263-3274
Several studies have demonstrated that N-substituted amino acid derivatives exhibit weak anticonvulsant activities in vivo. In the present study, a series of amides of aminoacids structurally related to aminoacetamide have been synthesised and investigated for anticonvulsant activity. Among the molecules investigated, those containing a bicyclic (tetralinyl, indanyl) group linked to the aminoacetamide chain (40, 47 and 59) were among the most active as anticonvulsants (ED50 > 10, <100 mg/kg after oral administration) against tonic seizures in the mouse maximal electroshock, bicuculline and picrotoxin tests at doses devoid of neurotoxic activity. Altogether, these results suggest the described compounds as a class of orally available anticonvulsants. The ability of these compounds to partially block veratridine-induced aspartate efflux from rat cortical synaptosomes suggests that their anticonvulsant activity may be only partly the consequence of an interaction with neuronal voltage-dependent sodium channels. Some of the most potent compounds appear worthy of a further investigation aimed at assessing their anticonvulsant activity in other models and at elucidating the underlying mechanism of action. 相似文献
94.
Guido Grassi Gino Seravalle Francesco Scopelliti Raffaella Dell'Oro Luca Fattori Fosca Quarti‐Trevano Gianmaria Brambilla Ernesto L. Schiffrin Giuseppe Mancia 《Obesity (Silver Spring, Md.)》2010,18(1):92-98
Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large‐ and medium‐size arteries. We hypothesized that normotensive subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 ± 2.9 years, BMI: 22.9 ± 0.3 kg/m2, mean ± s.e.m.) and 17 age‐matched severely obese (BMI: 41.1 ± 2.3 kg/m2) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross‐sectional area (CSA), and media‐to‐lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 ± 0.6 vs. 16.2 ± 0.6 µm, CSA 22,272 ± 1,339 vs. 15,183 ± 1,186 µm2, and media‐to‐lumen ratio 0.113 ± 0.006 vs. 0.059 ± 0.001, respectively, P < 0.01). Acetylcholine‐induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (?40.4 ± 1.3%, P < 0.01), whereas endothelium‐independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity. 相似文献
95.
Bhardwaj A Molineux IJ Casjens SR Cingolani G 《The Journal of biological chemistry》2011,286(35):30867-30877
Podoviridae are double-stranded DNA bacteriophages that use short, non-contractile tails to adsorb to the host cell surface. Within the tail apparatus of P22-like phages, a dedicated fiber known as the “tail needle” likely functions as a cell envelope-penetrating device to promote ejection of viral DNA inside the host. In Sf6, a P22-like phage that infects Shigella flexneri, the tail needle presents a C-terminal globular knob. This knob, absent in phage P22 but shared in other members of the P22-like genus, represents the outermost exposed tip of the virion that contacts the host cell surface. Here, we report a crystal structure of the Sf6 tail needle knob determined at 1.0 Å resolution. The structure reveals a trimeric globular domain of the TNF fold structurally superimposable with that of the tail-less phage PRD1 spike protein P5 and the adenovirus knob, domains that in both viruses function in receptor binding. However, P22-like phages are not known to utilize a protein receptor and are thought to directly penetrate the host surface. At 1.0 Å resolution, we identified three equivalents of l-glutamic acid (l-Glu) bound to each subunit interface. Although intimately bound to the protein, l-Glu does not increase the structural stability of the trimer nor it affects its ability to self-trimerize in vitro. In analogy to P22 gp26, we suggest the tail needle of phage Sf6 is ejected through the bacterial cell envelope during infection and its C-terminal knob is threaded through peptidoglycan pores formed by glycan strands. 相似文献
96.
Alexey Tomilov Ahmed Bettaieb Kyoungmi Kim Sunil Sahdeo Natalia Tomilova Adam Lam Kevork Hagopian Michelle Connell Jennifer Fong Douglas Rowland Stephen Griffey Jon Ramsey Fawaz Haj Gino Cortopassi 《Aging cell》2014,13(6):1049-1058
Adipose tissue is an important metabolic organ that integrates a wide array of homeostatic processes and is crucial for whole‐body insulin sensitivity and energy metabolism. Brown adipose tissue (BAT) is a key thermogenic tissue with a well‐established role in energy expenditure. BAT dissipates energy and protects against both hypothermia and obesity. Thus, BAT stimulation therapy is a rational strategy for the looming pandemic of obesity, whose consequences and comorbidities have a huge impact on the aged. Shc‐deficient mice (ShcKO) were previously shown to be lean, insulin sensitive, and resistant to high‐fat diet and obesity. We investigated the contribution of BAT to this phenotype. Insulin‐dependent BAT glucose uptake was higher in ShcKO mice. Primary ShcKO BAT cells exhibited increased mitochondrial respiration; increased expression of several mitochondrial and lipid‐oxidative enzymes was observed in ShcKO BAT. Levels of brown fat‐specific markers of differentiation, UCP1, PRDM16, ELOVL3, and Cox8b, were higher in ShcKO BAT. In vitro, Shc knockdown in BAT cell line increased insulin sensitivity and metabolic activity. In vivo, pharmacological stimulation of ShcKO BAT resulted in higher energy expenditure. Conversely, pharmacological inhibition of BAT abolished the improved metabolic parameters, that is the increased insulin sensitivity and glucose tolerance of ShcKO mice. Similarly, in vitro Shc knockdown in BAT cell lines increased their expression of UCP1 and metabolic activity. These data suggest increased BAT activity significantly contributes to the improved metabolic phenotype of ShcKO mice. 相似文献
97.
Paolo Martini Gabriele Sales Mattia Brugiolo Alessandro Gandaglia Filippo Naso Cristiano De Pittà Michele Spina Gino Gerosa Francesco Chemello Chiara Romualdi Stefano Cagnin Gerolamo Lanfranchi 《PloS one》2014,9(4)
Background
Despite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs) are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date.Results
We applied a novel computational approach to predict species-specific and conserved miRNAs in the pig genome, which were then subjected to experimental validation. We experimentally identified candidate miRNAs sequences grouped in high-confidence (424) and medium-confidence (353) miRNAs according to RNA-seq results. A group of miRNAs was also validated by PCR experiments. We established the subtle variability in expression of isomiRs and miRNA-miRNA star couples supporting a biological function for these molecules. Finally, miRNA and mRNA expression profiles produced from the same sample of 20 different tissue of the animal were combined, using a correlation threshold to filter miRNA-target predictions, to identify tissue-specific regulatory networks.Conclusions
Our data represent a significant progress in the current understanding of miRNAome in pig. The identification of miRNAs, their target mRNAs, and the construction of regulatory circuits will provide new insights into the complex biological networks in several tissues of this important animal model. 相似文献98.
Yeojin Sung Seungbin Cha Sang Bum Kim Hakhyun Kim Seonghwi Choi Sejin Oh Minseo Kim Yunji Lee Gino Kwon Jooyoung Lee Joo-Youn Lee Gyoonhee Han Hyun Seok Kim 《BMB reports》2022,55(12):645
Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development. 相似文献
99.
100.
There is no current approved therapy for the ultimately lethal neuro- and cardio-degenerative disease Friedreich''s ataxia (FA). Finding minimally-invasive molecular biomarkers of disease progression and drug effect could support smaller, shorter clinical trials. Since we and others have noted a deficient oxidative stress response in FA, we investigated the expression of 84 genes involved in oxidative stress, signaling, and protection in control and FA lymphoblasts ranging from 460 to 1122 GAA repeats. Several antioxidant genes responded in a dose-dependent manner to frataxin expression at the mRNA and protein levels, which is inversely correlated with disease progression and severity. We tested the effect of experimental Friedreich’s ataxia therapies dimethyl fumarate (DMF) and type 1 histone deacetylase inhibitor (HDACi) on biomarker mRNA expression. We observed that exposure of lymphoblasts to DMF and HDACi dose-dependently unsilenced frataxin expression and restored the potential biomarkers NCF2 and PDLIM1 expression to control levels. We suggest that in addition to frataxin expression, blood lymphoblast levels of NCF2 and PDLIM1 could be useful biomarkers for disease progression and drug effect in future clinical trials of Friedreich’s ataxia. 相似文献