排序方式: 共有153条查询结果,搜索用时 15 毫秒
91.
Ghania Ramdani Bernina Naissant Eloise Thompson Florence Breil Audrey Lorthiois Florian Dupuy Ross Cummings Yoann Duffier Yolanda Corbett Odile Mercereau-Puijalon Kenneth Vernick Donatella Taramelli David A. Baker Gordon Langsley Catherine Lavazec 《PLoS pathogens》2015,11(5)
Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites. 相似文献
92.
Laia Richart Eleonora Lapi Vera Pancaldi Mirabai Cuenca-Ardura Enrique
Carrillo-de-Santa Pau Miguel Madrid-Mencía Hlne Neyret-Kahn Franois Radvanyi Juan
Antonio Rodríguez Yasmina Cuartero Franois Serra Franois Le
Dily Alfonso Valencia Marc
A Marti-Renom Francisco
X Real 《Nucleic acids research》2021,49(19):11005
93.
94.
Teodora Djikic Yasmina Martí Francesca Spyrakis Thorsten Lau Paolo Benedetti Gavin Davey 《Journal of biomolecular structure & dynamics》2019,37(2):291-306
Parkinson’s disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra and corpus striatum. Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required. By means of homology modeling, molecular docking, and molecular dynamics simulations, we have generated 3D structure models of hDAT in complex with substrate and inhibitors. Our results clearly reveal differences in binding affinity of these compounds to the hDAT in the open and closed conformations, critical for future drug design. The established in silico approach allowed the identification of promising substrate compounds that were subsequently analyzed for their efficiency in inhibiting hDAT-dependent fluorescent substrate uptake, through in vitro live cell imaging experiments. Taken together, our work presents the first implementation of a combined in silico/in vitro approach enabling the selection of promising dopaminergic neuron-specific substrates. 相似文献
95.
Yasmina Hamouche Nabila Amirouche Marie-Thérèse Misset Rachid Amirouche 《Plant Systematics and Evolution》2010,285(3-4):177-187
Cytotaxonomic investigations of the autumn-flowering squills, Prospero autumnale (L.) Speta ≡ Scilla autumnalis L., Prospero obtusifolium (Poir.) Speta ≡ Scilla obtusifolia Poir., Barnardia numidica (Poir.) Speta ≡ Scilla numidica Poir., and Hyacinthoides lingulata (Poir.) Rothm. ≡ Scilla lingulata Poir. were performed in 20 populations from northern Algeria located between Tipasa and La Vieille Calle. Various chromosome numbers were found, including a new cytotype, 2n = 8, for the flora of Algeria, concerning plants identified as Prospero obtusifolium (Poir.) Speta [including P. fallax (Steinh.) Speta = S. autumnalis L. ssp. fallax (Steinh.) Batt.]. The numbers 2n = 14, 28, and 42 correspond, respectively, to diploid, tetraploid, and hexaploid levels of P. autumnale s.l. [including P. pulchellum (Munby) Speta ≡ Scilla pulchella Munby = S. autumnalis var. pulchella (Munby) Batt.], with x = 7. The cytotypes of Barnardia numidica (Poir.) Speta with 2n = 18 and Hyacinthoides lingulata (Poir.) Rothm. with 2n = 16 chromosomes were confirmed. 相似文献
96.
Zhai W Glanville J Fuhrmann M Mei L Ni I Sundar PD Van Blarcom T Abdiche Y Lindquist K Strohner R Telman D Cappuccilli G Finlay WJ Van den Brulle J Cox DR Pons J Rajpal A 《Journal of molecular biology》2011,412(1):55-71
We present a method for synthetic antibody library generation that combines the use of high-throughput immune repertoire analysis and a novel synthetic technology. The library design recapitulates positional amino acid frequencies observed in natural antibody repertoires. V-segment diversity in four heavy (VH) and two kappa (Vκ) germlines was introduced based on the analysis of somatically hypermutated donor-derived repertoires. Complementarity-determining region 3 length and amino acid designs were based on aggregate frequencies of all VH and Vκ sequences in the data set. The designed libraries were constructed through an adaptation of a novel gene synthesis technology that enables precise positional control of amino acid composition and incorporation frequencies. High-throughput pyrosequencing was used to monitor the fidelity of construction and characterize genetic diversity in the final 3.6 × 1010 transformants. The library exhibited Fab expression superior to currently reported synthetic approaches of equivalent diversity, with greater than 93% of clones observed to successfully display both a correctly folded heavy chain and a correctly folded light chain. Genetic diversity in the library was high, with 95% of 7.0 × 105 clones sequenced observed only once. The obtained library diversity explores a comparable sequence space as the donor-derived natural repertoire and, at the same time, is able to access novel recombined diversity due to lack of segmental linkage. The successful isolation of low- and subnanomolar-affinity antibodies against a diverse panel of receptors, growth factors, enzymes, antigens from infectious reagents, and peptides confirms the functional viability of the design strategy. 相似文献
97.
Dunham WH Larsen B Tate S Badillo BG Goudreault M Tehami Y Kislinger T Gingras AC 《Proteomics》2011,11(13):2603-2612
Affinity purification coupled to mass spectrometry (AP-MS) is gaining widespread use for the identification of protein-protein interactions. It is unclear, however, whether typical AP sample complexity is limiting for the identification of all protein components using standard one-dimensional LC-MS/MS. Multidimensional sample separation is useful for reducing sample complexity prior to MS analysis and increases peptide and protein coverage of complex samples. Here, we monitored the effects of upstream protein or peptide separation techniques on typical mammalian AP-MS samples, generated by FLAG affinity purification of four baits with different biological functions and/or subcellular distribution. As a first separation step, we employed SDS-PAGE, strong cation exchange LC, or reversed-phase LC at basic pH. We also analyzed the benefits of using an instrument with a faster scan rate, the new TripleTOF 5600 mass spectrometer. While all multidimensional approaches yielded a clear increase in spectral counts, the increase in unique peptides and additional protein identification was modest and came at the cost of increased instrument and handling time. The use of a high duty-cycle instrument achieved similar benefits without these drawbacks. An increase in spectral counts is beneficial when data analysis methods relying on spectral counts, including Significance Analysis of INTeractome (SAINT), are used. 相似文献
98.
Lily Mijouin Mélanie Hillion Yasmina Ramdani Thomas Jaouen Cécile Duclairoir-Poc Marie-Laure Follet-Gueye Elian Lati Florent Yvergnaux Azzedine Driouich Luc Lefeuvre Christine Farmer Laurent Misery Marc G. J. Feuilloley 《PloS one》2013,8(11)
Background
Skin is the largest human neuroendocrine organ and hosts the second most numerous microbial population but the interaction of skin neuropeptides with the microflora has never been investigated. We studied the effect of Substance P (SP), a peptide released by nerve endings in the skin on bacterial virulence.Methodology/Principal Findings
Bacillus cereus, a member of the skin transient microflora, was used as a model. Exposure to SP strongly stimulated the cytotoxicity of B. cereus (+553±3% with SP 10−6 M) and this effect was rapid (<5 min). Infection of keratinocytes with SP treated B. cereus led to a rise in caspase1 and morphological alterations of the actin cytoskeleton. Secretome analysis revealed that SP stimulated the release of collagenase and superoxide dismutase. Moreover, we also noted a shift in the surface polarity of the bacteria linked to a peel-off of the S-layer and the release of S-layer proteins. Meanwhile, the biofilm formation activity of B. cereus was increased. The Thermo unstable ribosomal Elongation factor (Ef-Tu) was identified as the SP binding site in B. cereus. Other Gram positive skin bacteria, namely Staphylococcus aureus and Staphylococcus epidermidis also reacted to SP by an increase of virulence. Thermal water from Uriage-les-Bains and an artificial polysaccharide (Teflose®) were capable to antagonize the effect of SP on bacterial virulence.Conclusions/Significance
SP is released in sweat during stress and is known to be involved in the pathogenesis of numerous skin diseases through neurogenic inflammation. Our study suggests that a direct effect of SP on the skin microbiote should be another mechanism. 相似文献99.
Bonnet V Ramdani S Fraisse P Ramdani N Lagarde J Bardy BG 《Journal of biomechanics》2011,44(11):2123-2128
This paper proposes a closed-loop optimal control model predicting changes between in-phase and anti-phase postural coordination during standing and related supra-postural activities. The model allows the evaluation of the influence of body dynamics and balance constraints onto the adoption of postural coordination. This model minimizes the instantaneous norm of the joint torques with a controller in the head space, in contrast with classical linear optimal models used in the postural literature and defined in joint space. The balance constraint is addressed with an adaptive ankle torque saturation. Numerical simulations showed that the model was able to predict changes between in-phase and anti-phase postural coordination modes and other non-linear transient dynamics phenomena. 相似文献
100.
Richard W. D. Welford Marco Garzotti Charles Marques Louren?o Eugen Mengel Thorsten Marquardt Janine Reunert Yasmina Amraoui Stefan A. Kolb Olivier Morand Peter Groenen 《PloS one》2014,9(12)
Niemann-Pick disease type C (NP-C) is a devastating, neurovisceral lysosomal storage disorder which is characterised by variable manifestation of visceral signs, progressive neuropsychiatric deterioration and premature death, caused by mutations in the NPC1 and NPC2 genes. Due to the complexity of diagnosis and the availability of an approved therapy in the EU, improved detection of NP-C may have a huge impact on future disease management. At the cellular level dysfunction or deficiency of either the NPC1 or NPC2 protein leads to a complex intracellular endosomal/lysosomal trafficking defect, and organ specific patterns of sphingolipid accumulation. Lysosphingolipids have been shown to be excellent biomarkers of sphingolipidosis in several enzyme deficient lysosomal storage disorders. Additionally, in a recent study the lysosphingolipids, lysosphingomyelin (SPC) and glucosylsphingosine (GlcSph), appeared to be elevated in the plasma of three adult NP-C patients. In order to investigate the clinical utility of SPC and GlcSph as diagnostic markers, an in-depth fit for purpose biomarker assay validation for measurement of these biomarkers in plasma by liquid chromatography-tandem mass spectrometry was performed. Plasma SPC and GlcSph are stable and can be measured accurately, precisely and reproducibly. In a retrospective analysis of 57 NP-C patients and 70 control subjects, median plasma SPC and GlcSph were significantly elevated in NP-C by 2.8-fold and 1.4-fold respectively. For miglustat-naïve NP-C patients, aged 2–50 years, the area under the ROC curve was 0.999 for SPC and 0.776 for GlcSph. Plasma GlcSph did not correlate with SPC levels in NP-C patients. The data indicate excellent potential for the use of lysosphingomyelin in NP-C diagnosis, where it could be used to identify NP-C patients for confirmatory genetic testing. 相似文献