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101.
Francesco Infarinato Anisur Rahman Claudio Del Percio Yves Lamberty Regis Bordet Jill C. Richardson Gianluigi Forloni Wilhelmus Drinkenburg Susanna Lopez Fabienne Aujard Claudio Babiloni Fabien Pifferi IMI project "PharmaCog" Consortium 《PloS one》2015,10(11)
The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8–12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7–9 Hz) during passive state. During active state, there was a reduction in alpha power density (8–12 Hz) and an increase of power density at slow frequencies (1–4 Hz). Relative EMG activity was related to EEG power density at 2–4 Hz (positive correlation) and at 8–12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology. 相似文献
102.
Clara Braian Mattias Svensson Susanna Brighenti Maria Lerm Venkata R. Parasa 《Journal of visualized experiments : JoVE》2015,(104)
Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs. 相似文献
103.
Seema Singh Susanna A. Braus-Stromeyer Christian Timpner Van Tuan Tran Gertrud Lohaus Michael Reusche Jessica Knüfer Thomas Teichmann Andreas von Tiedemann Gerhard H. Braus 《Applied microbiology and biotechnology》2010,85(6):1961-1976
The first leaky auxotrophic mutant for aromatic amino acids of the near-diploid fungal plant pathogen Verticillium longisporum (VL) has been generated. VL enters its host Brassica napus through the roots and colonizes the xylem vessels. The xylem contains little nutrients including low concentrations of amino
acids. We isolated the gene Vlaro2 encoding chorismate synthase by complementation of the corresponding yeast mutant strain. Chorismate synthase produces the
first branch point intermediate of aromatic amino acid biosynthesis. A novel RNA-mediated gene silencing method reduced gene
expression of both isogenes by 80% and resulted in a bradytrophic mutant, which is a leaky auxotroph due to impaired expression
of chorismate synthase. In contrast to the wild type, silencing resulted in increased expression of the cross-pathway regulatory
gene VlcpcA (similar to cpcA/GCN4) during saprotrophic life. The mutant fungus is still able to infect the host plant B. napus and the model Arabidopsis thaliana with reduced efficiency. VlcpcA expression is increased in planta in the mutant and the wild-type fungus. We assume that xylem colonization requires induction
of the cross-pathway control, presumably because the fungus has to overcome imbalanced amino acid supply in the xylem. 相似文献
104.
105.
Magda Gioia Giovanni Francesco Fasciglione Susanna Monaco Riccardo Iundusi Diego Sbardella Stefano Marini Umberto Tarantino Massimo Coletta 《Journal of biological inorganic chemistry》2010,15(8):1219-1232
The proteolytic processing of collagen I by three matrix metalloproteinases (MMPs), a collagenase (MMP-1), a gelatinase (MMP-2),
and the ectodomain of a membrane-type metalloproteinase (MMP-14), has been investigated at 37 °C between pH 6.0 and 9.2, a
pH range reflecting conditions found in different body compartments under various physiopathological processes. In the proteolytic
degradation the native collagen triple helix must be partially unwound to allow the binding of α chains to the protease’s
active-site cleft. We have found that MMP-1 interacts with the two types of collagen I α chains in a similar fashion, whereas
both MMP-2 and MMP-14 bind the two α chains in a different way. The overall enzymatic activity is higher on the α-2 chain
for both MMP-1 and MMP-2, whereas the MMP-14 ectodomain preferentially cleaves the α-1 chain. In MMP-2 a marked difference
for substrate affinity (higher for the α-1 chain) is overwhelmed by an even more marked propensity to cleave the α-2 chain.
As a whole, the three classes of MMPs investigated appear to process collagen I in a significantly different fashion, so various
MMPs play different roles in the collagen homeostasis in various compartments (such as bloodstream, synovial fluid, normal
and tumoral tissues), where different pH values are observed. 相似文献
106.
Cilurzo F Cupone IE Minghetti P Buratti S Selmin F Gennari CG Montanari L 《AAPS PharmSciTech》2010,11(4):1511-1517
This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine
hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and
the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose
equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film
tensile properties. The bitterness and astringency intensity of NHT and the suppression effect of several TMA were evaluated
by a Taste-Sensing System. The films were characterised in term of NHT content, tensile properties, disintegration time and
drug dissolution test. As expected, placebo films made of MDX DE 6 appeared stiffer and less ductile than film prepared using
MDX DE 12. The films disintegrated within 10 s. Among the tested TMA, the milk and mint flavours resulted particularly suitable
to mask the taste of NHT. The addition of NHT and taste-masking agents affected film tensile properties; however, the effect
of the addition of these components can be counterweighted by modulating the glycerine content and/or the MDX molecular weight.
The feasibility of NHT loaded fast-dissolving films was demonstrated. 相似文献
107.
108.
109.
ZAMORANO JOSE Unidad de Investigacion Hospital San Pedro de Alcantara Avda Millan Astray Caceres ANN E KELLY JONATHAN AUSTRIAN HELEN Y WANG ACHSAH D KEEGAN 《Cell research》2001,(1)
INTRODUCTIONThe inappropriate enhancement of lymphocytesurviVal due to a block in programmed cell deathand/or an enhancement of entry into the cell cyclecan contribute to the abnormal expansion of clonesresulting in tumorigenesis or the breakdown of pe-ripheral self-toleranced, 2]. Proper lymphocytehomeostasis is critical for normal immune functionand is maintained by a complex series of cellularinteractions and the action of secreted cytokines.Illterleukin-4 (IL-4), a cytokine produced … 相似文献
110.
J Perez-Gil EM Uros S Sauret-Güeto LM Lois J Kirby M Nishimoto EE Baidoo JD Keasling A Boronat M Rodriguez-Concepcion 《PloS one》2012,7(8):e43775
A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway. 相似文献