排序方式: 共有71条查询结果,搜索用时 15 毫秒
21.
Kumari R Tecon R Beggah S Rutler R Arey JS van der Meer JR 《Environmental microbiology》2011,13(10):2808-2819
Long-chain alkanes are a major component of crude oil and therefore potentially good indicators of hydrocarbon spills. Here we present a set of new bacterial bioreporters and assays that allow to detect long-chain alkanes. These reporters are based on the regulatory protein AlkS and the alkB1 promoter from Alcanivorax borkumensis SK2, a widespread alkane degrader in marine habitats. Escherichia coli cells with the reporter construct reacted strongly to octane in short-term (6 h) aqueous suspension assays but very slightly only to tetradecane, in line with what is expected from its low water solubility. In contrast, long-term assays (up to 5 days) with A. borkumensis bioreporters showed strong induction with tetradecane and crude oil. Gel-immobilized A. borkumensis reporter cells were used to demonstrate tetradecane and crude oil bioavailability at a distance from a source. Alcanivorax borkumensis bioreporters induced fivefold more rapid and more strongly when allowed physical contact with the oil phase in standing flask assays, suggesting a major contribution of adhered cells to the overall reporter signal. Using the flask assays we further demonstrated the effect of oleophilic nutrients and biosurfactants on oil availability and degradation by A. borkumensis. The fluorescence signal from flask assays could easily be captured with a normal digital camera, making such tests feasible to be carried out on, e.g. marine oil responder vessels in case of oil accidents. 相似文献
22.
Siham A. Alissa Hanan A. Alghulikah Zeid A. ALOthman Sameh M. Osman Sonia Del Prete Clemente Capasso 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):377-382
Abstract The inhibition of δ- and η-class carbonic anhydrases (CAs; EC 4.2.1.1) was poorly investigated so far. Only one δ-CA, TweCA from the diatom Thalassiosira weissflogii, and one η-CA, PfCA, from Plasmodium falciparum, have been cloned and characterised to date. To enrich δ- and η-CAs inhibition profiles, a panel of 22 phenols was investigated for TweCA and PfCA inhibition. Some derivatives showed effective, sub-micromolar inhibition of TweCA (KIs 0.81–65.4?µM) and PfCA (KIs 0.62–78.7?µM). A subset of compounds demonstrated a significant selectivity for the target CAs over the human physiologically relevant ones. This study promotes the identification of new potent and selective inhibitors of TweCA and PfCA, which could be considered as leads for finding molecular probes in the study of carbon fixation processes (in which TweCA and orthologue enzymes are involved) or drug candidates in the treatment of malaria. 相似文献
23.
Shovonlal Bhowmick Siham A. Alissa Saikh Mohammad Wabaidur Rupesh V. Chikhale Md Ataul Islam 《Journal of molecular recognition : JMR》2020,33(7)
Dengue infection is the most common arthropod‐borne disease caused by dengue viruses, predominantly affecting millions of human beings annually. To find out promising chemical entities for therapeutic application in Dengue, in the current research, a multi‐step virtual screening effort was conceived to screen out the entire “screening library” of the Asinex database. Initially, through “Lipinski rule of five” filtration criterion almost 0.6 million compounds were collected and docked with NS3‐NS2B protein. Thereby, the chemical space was reduced to about 3500 compounds through the analysis of binding affinity obtained from molecular docking study in AutoDock Vina. Further, the “Virtual Screening Workflow” (VSW) utility of Schrödinger suite was used, which follows a stepwise multiple docking programs such as ‐ high‐throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking, and in postprocessing analysis the MM‐GBSA based free binding energy calculation. Finally, five potent molecules were proposed as potential inhibitors for the dengue NS3‐NS2B protein based on the investigation of molecular interactions map and protein‐ligand fingerprint analyses. Different pharmacokinetics and drug‐likeness parameters were also checked, which favour the potentiality of selected molecules for being drug‐like candidates. The molecular dynamics (MD) simulation analyses of protein‐ligand complexes were explained that NS3‐NS2B bound with proposed molecules quite stable in dynamic states as observed from the root means square deviation (RMSD) and root means square fluctuation (RMSF) parameters. The binding free energy was calculated using MM‐GBSA method from the MD simulation trajectories revealed that all proposed molecules possess such a strong binding affinity towards the dengue NS3‐NS2B protein. Therefore, proposed molecules may be potential chemical components for effective inhibition of dengue NS3‐NS2B protein subjected to experimental validation. 相似文献
24.
Ramsingh R Grygorczyk A Solecki A Cherkaoui LS Berthiaume Y Grygorczyk R 《American journal of physiology. Lung cellular and molecular physiology》2011,300(4):L587-L595
Extracellular nucleotides regulate mucociliary clearance in the airways and surfactant secretion in alveoli. Their release is exquisitely mechanosensitive and may be induced by stretch as well as airflow shear stress acting on lung epithelia. We hypothesized that, in addition, tension forces at the air-liquid interface (ALI) may contribute to mechanosensitive ATP release in the lungs. Local depletion of airway surface liquid, mucins, and surfactants, which normally protect epithelial surfaces, facilitate such release and trigger compensatory mucin and fluid secretion processes. In this study, human bronchial epithelial 16HBE14o(-) and alveolar A549 cells were subjected to tension forces at the ALI by passing an air bubble over the cell monolayer in a flow-through chamber, or by air exposure while tilting the cell culture dish. Such stimulation induced significant ATP release not involving cell lysis, as verified by ethidium bromide staining. Confocal fluorescence microscopy disclosed reversible cell deformation in the monolayer part in contact with the ALI. Fura 2 fluorescence imaging revealed transient intracellular Ca(2+) elevation evoked by the ALI, which did not entail nonspecific Ca(2+) influx from the extracellular space. ATP release was reduced by ~40 to ~90% from cells loaded with the Ca(2+) chelator BAPTA-AM and was completely abolished by N-ethylmalemide (1 mM). These experiments demonstrate that in close proximity to the ALI, surface tension forces are transmitted directly on cells, causing their mechanical deformation and Ca(2+)-dependent exocytotic ATP release. Such a signaling mechanism may contribute to the detection of local deficiency of airway surface liquid and surfactants on the lung surface. 相似文献
25.
Samir Zouhri Denis Geraads Siham El Boughabi Abdelghani El Harfi 《Comptes Rendus Palevol》2012,11(6):455-461
The discovery of Upper Miocene vertebrates at Tizi N’Tadderht in the Ouarzazate basin (Morocco) helps to fill a gap in our knowledge of Neogene faunas in North Africa. The new fauna includes an ostrich cf. Struthio sp, a turtle cf. Centrochelys sp., Crocodylus cf. niloticus, and a relatively diverse fauna of large mammals. The mammal assemblage probably includes three hipparion species, including a very small form not previously reported from Africa, aff. Cremohipparion periafricanum, two species of rhinoceros cf. Ceratotherium sp. and aff. Chilotherium sp., a Proboscidean cf. Tetralophodon sp., a large member of the Giraffidae similar to “Palaeotragus” germaini and two bovids of which one is likely related to Prostrepsiceros, while the other is a new medium-sized antelope with spiral horns, certainly a representative of the Caprinae, a group that is rare in Africa. A late Miocene age, corresponding to the European Turolian Mammal age, is most likely for this fauna. 相似文献
26.
Rais G Raissouni S Mouzount H Aitelhaj M Khoyaali S El Omrani F Mrabti H Jelthi A Errihani H 《Journal of medical case reports》2012,6(1):101-7
Introduction
Leiomyosarcomas are neoplasms of smooth muscles that most commonly arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases have been published to date. Because of the rarity of pleural leiomyosarcoma and its similarity (clinical and histological) to other pleural neoplasms, particularly sarcomatous mesothelioma, diagnosis is often difficult.Case presentation
A 58-year-old North African man was admitted with complaints of dyspnea and chest pain to our hospital. Chest computed tomography revealed right pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive for vimentin, a smooth muscle actin at immunohistochemical analysis. A general examination did not show any metastatic lesions in other areas. One month after diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma.Conclusions
Although leiomyosarcoma originating from the pleura is rare, this entity is increasingly described. The purpose of presenting this case report is to raise awareness among clinicians to consider this clinical entity as a differential diagnosis when a pleural mass is identified. 相似文献27.
Cyrille Deboux Sophia Ladraa Sylvie Cazaubon Siham Ghribi-Mallah Nicolas Weiss Nathalie Chaverot Pierre Olivier Couraud Anne Baron-Van Evercooren 《PloS one》2013,8(2)
Neural precursor (NPC) based therapies are used to restore neurons or oligodendrocytes and/or provide neuroprotection in a large variety of neurological diseases. In multiple sclerosis models, intravenously (i.v) -delivered NPCs reduced clinical signs via immunomodulation. We demonstrated recently that NPCs were able to cross cerebral endothelial cells in vitro and that the multifunctional signalling molecule, CD44 involved in trans-endothelial migration of lymphocytes to sites of inflammation, plays a crucial role in extravasation of syngeneic NPCs. In view of the role of CD44 in NPCs trans-endothelial migration in vitro, we questioned presently the benefit of CD44 overexpression by NPCs in vitro and in vivo, in EAE mice. We show that overexpression of CD44 by NPCs enhanced over 2 folds their trans-endothelial migration in vitro, without impinging on the proliferation or differentiation potential of the transduced cells. Moreover, CD44 overexpression by NPCs improved significantly their elongation, spreading and number of filopodia over the extracellular matrix protein laminin in vitro. We then tested the effect of CD44 overexpression after i.v. delivery in the tail vein of EAE mice. CD44 overexpression was functional invivo as it accelerated trans-endothelial migration and facilitated invasion of HA expressing perivascular sites. These in vitro and in vivo data suggest that CD44 may be crucial not only for NPC crossing the endothelial layer but also for facilitating invasion of extravascular tissues. 相似文献
28.
Kristin Schram Sabrina De Girolamo Siham Madani Diana Munoz Farah Thong Gary Sweeney 《Cellular & molecular biology letters》2010,15(4):551-563
A clear association between obesity and heart failure exists and a significant role for leptin, the product of the obese gene,
has been suggested. One aspect of myocardial remodeling which characterizes heart failure is a disruption in the balance of
extracellular matrix synthesis and degradation. Here we investigated the effects of leptin on matrix metalloproteinase (MMP)
activity, tissue inhibitor of metalloproteinase (TIMP) expression, as well as collagen synthesis in HL-1 cardiac muscle cells.
Gelatin zymographic analysis of MMP activity in conditioned media showed that leptin enhanced MMP-2 activity in a dose- and
time-dependent manner. Leptin is known to stimulate phosphorylation of p38 MAPK in cardiac cells and utilization of the p38
MAPK inhibitor, SB203580, demonstrated that this kinase also plays a role in regulating several extracellular matrix components,
such that inhibition of p38 MAPK signaling prevented the leptin-induced increase in MMP-2 activation. We also observed that
leptin enhanced collagen synthesis determined by both proline incorporation and picrosirius red staining of conditioned media.
Pro-collagen type-I and pro-collagen type-III expression, measured by real-time PCR and Western blotting were also increased
by leptin, effects which were again attenuated by SB203580. In summary, these results demonstrate the potential for leptin
to play a role in mediating myocardial ECM remodeling and that the p38 MAPK pathway plays an important role in mediating these
effects. 相似文献
29.
Stephane Renauld Karine Tremblay Siham Ait-Benichou Maxime Simoneau-Roy Hugo Garneau Olivier Staub Ahmed Chraïbi 《The Journal of membrane biology》2010,236(3):259-270
Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists used to treat type 2 diabetes.
TZD treatment induces side effects such as peripheral fluid retention, often leading to discontinuation of therapy. Previous
studies have shown that PPARγ activation by TZD enhances the expression or function of the epithelial sodium channel (ENaC)
through different mechanisms. However, the effect of TZDs on ENaC activity is not clearly understood. Here, we show that treating
Xenopus
laevis oocytes expressing ENaC and PPARγ with the TZD rosiglitazone (RGZ) produced a twofold increase of amiloride-sensitive sodium
current (Iam), as measured by two-electrode voltage clamp. RGZ-induced ENaC activation was PPARγ-dependent since the PPARγ antagonist
GW9662 blocked the activation. The RGZ-induced Iam increase was not mediated through direct serum- and glucocorticoid-regulated kinase (SGK1)-dependent phosphorylation of
serine residue 594 on the human ENaC α-subunit but by the diminution of ENaC ubiquitination through the SGK1/Nedd4-2 pathway.
In accordance, RGZ increased the activity of ENaC by enhancing its cell surface expression, most probably indirectly mediated
through the increase of SGK1 expression. 相似文献
30.
David Lesniak Siham Sabri Yaoxian Xu Kathryn Graham Pravin Bhatnagar Mavanur Suresh Bassam Abdulkarim 《PloS one》2013,8(8)
Resistance to trastuzumab, a rationally designed HER-2-targeting antibody, remains a major hurdle in the management of HER-2-positive breast cancer. Preclinical studies suggest the mechanisms of trastuzumab resistance are numerous. Unfortunately, the majority of these studies are based around HER-2-positive (HER-2+) luminal cell lines. The role of epithelial to mesenchymal transition (EMT), a genetic program that confers a basal phenotype, may represent a novel mechanism of escape for HER-2+ luminal cells from trastuzumab treatment. Here we investigated this possibility using a model of clonal selection in HER-2+ luminal breast cancer cells. Following a random isolation and expansion of “colony clusters” from SKBR-3 cell lines, several colony clusters underwent a spontaneous EMT in-vitro. In addition to expression of conventional EMT markers, all mesenchymal colony clusters displayed a predominant CD44+/CD24- phenotype with decreased HER-2 expression and elevated levels of a β1-integrin isoform with a high degree of N-glycosylation. Treatment with a β1-integrin function-blocking antibody, AIIB2, preferentially decreased the N-glycosylated form of β1-integrin, impaired mammosphere formation and restored epithelial phenotype in mesenchymal colony clusters. Using this model we provide the first clear evidence that resistance to trastuzumab (and lapatinib) can occur spontaneously as HER-2+ cells shift from a luminal to a basal/mesenchymal phenotype following EMT. While the major determinant of trastuzumab resistance in mesenchymal colony clusters is likely the down regulation of the HER-2 protein, our evidence suggests that multiple factors may contribute, including expression of N-glycosylated β1-integrin. 相似文献