Analysis of the Rickettsia africae genome reveals that virulence acquisition in Rickettsia species may be explained by genome reduction

<p>Abstract</p> <p>Background</p> <p>The <it>Rickettsia </it>genus includes 25 validated species, 17 of which are proven human pathogens. Among these, the pathogenicity varies greatly, from the highly virulent <it>R. prowazekii</it>, which causes epidemic typhus and kills its arthropod host, to the mild pathogen <it>R. africae</it>, the agent of African tick-bite fever, which does not affect the fitness of its tick vector.</p> <p>Results</p> <p>We evaluated the clonality of <it>R. africae </it>in 70 patients and 155 ticks, and determined its genome sequence, which comprises a circular chromosome of 1,278,540 bp including a <it>tra </it>operon and an unstable 12,377-bp plasmid. To study the genetic characteristics associated with virulence, we compared this species to <it>R. prowazekii</it>, <it>R. rickettsii </it>and <it>R. conorii</it>. <it>R. africae </it>and <it>R. prowazekii </it>have, respectively, the less and most decayed genomes. Eighteen genes are present only in <it>R. africae </it>including one with a putative protease domain upregulated at 37°C.</p> <p>Conclusion</p> <p>Based on these data, we speculate that a loss of regulatory genes causes an increase of virulence of rickettsial species in ticks and mammals. We also speculate that in <it>Rickettsia </it>species virulence is mostly associated with gene loss.</p> <p>The genome sequence was deposited in GenBank under accession number [GenBank: <ext-link ext-link-type="gen" ext-link-id="NZ_AAUY01000001">NZ_AAUY01000001</ext-link>].</p

Large and Versatile Plasmonic Enhancement of Photoluminescence Using Colloidal Metallic Nanocubes

Improving phosphor photoluminescence efficiency is a key parameter to boost the performances of many optical devices. In this work, colloidal silver nanocubes, homogeneously spread on a luminescent surface, have proved to help both injecting and extracting light in and out of the photoluminescent layer and hence contributed significantly to the enhancement of the fluorescence. This approach has been applied to two materials: the well-known Y$_3$Al$_5$O$_{12}$:Ce yellow phosphor and an optical quartz. The emission efficiency, for sol-gel derived YAG:Ce layers, has increased of 80\% in the presence of an optimal nanoparticle density -- whereas for quartz, a weakly fluorescent material, the photoluminescence signal can be enhanced by a 200-fold factor. A physical analysis based on simulations shows that the disorder is an important factor and that the surface density of Ag nanoparticles is a crucial parameter

Shear-induced reinforcement in boehmite gels: a rheo-X-ray-scattering study

Boehmite, an aluminum oxide hydroxide $\gamma$-AlO(OH), is broadly used in the form of particulate dispersions in industrial applications, e.g., for the fabrication of ceramics and catalyst supports or as a binder for extrusion processes. Under acidic conditions, colloidal boehmite dispersions at rest form gels, i.e., space-spanning percolated networks that behave as soft solids at rest, and yet yield and flow like liquids under large enough deformations. Like many other colloidal gels, the solid-like properties of boehmite gels at rest are very sensitive to their previous mechanical history. Our recent work [Sudreau et al., J. Rheol. 66, 91-104 (2022), and Phys. Rev. Material 6, L042601 (2022)] has revealed such \textit{memory effects}, where the shear experienced prior to flow cessation drives the elasticity of boehmite gels: while gels formed following application of a shear rate $\dot\gamma_{\rm p}$ larger than a critical value $\dot\gamma_{\rm c}$ are insensitive to shear history, gels formed after application of $\dot\gamma_{\rm p}<\dot\gamma_{\rm c}$ display reinforced viscoelastic properties and non-negligible residual stresses. Here, we provide a microstructural scenario for these striking observations by coupling rheometry and small-angle X-ray scattering. Time-resolved measurements for $\dot\gamma_{\rm p} <\dot\gamma_{\rm c}$ show that scattering patterns develop an anisotropic shape that persists upon flow cessation, whereas gels exposed to $\dot\gamma_{\rm p}>\dot\gamma_{\rm c}$ display isotropic scattering patterns upon flow cessation. Moreover, as the shear rate applied prior to flow cessation is decreased below $\dot\gamma_{\rm c}$, the level of anisotropy frozen in the sample microstructure grows similarly to the viscoelastic properties, thus providing a direct link between mechanical reinforcement and flow-induced microstructural anisotropy.Comment: 13 pages, 10 figure

Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>The aim of the present work was to assess i) <it>ex vivo </it>activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 <it>Plasmodium falciparum </it>isolates from African countries, India and Thailand, and iii) <it>in vitro </it>cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).</p> <p>Methods</p> <p>The susceptibility of the 181 <it>P. falciparum </it>isolates to the nine anti-malarial drugs was assessed using the standard 42-hours ³H-hypoxanthine uptake inhibition method.</p> <p>Results</p> <p>The IC₅₀values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (<it>rho </it>= 0.46) and between PPQ and MDAQ (<it>rho </it>= 0.30). No significant correlation was shown between PPQ IC₅₀and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (<it>rho </it>= 0.37), PND and LMF (<it>rho </it>= 0.28), PND and QN (<it>rho </it>= 0.24), PND and AS (<it>rho </it>= 0.19), PND and DHA (<it>rho </it>= 0.18) and PND and CQ (<it>rho </it>= 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs.</p> <p>Conclusions</p> <p>In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs.</p

Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity

The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease

Etude de l'influence de la structure et de la composition de matériaux hybrides monolithiques sur les propriétés optiques (luminescence et absorption non-linéaire)

Le procédé sol-gel permet la réalisation de matériaux optiquement performants et la possibilité d intégrer diverses molécules dans ces systèmes ouvre les portes à des applications dans de nombreux domaines. Nous nous sommes intéressés en particulier à la réalisation de matériaux sol-gel monolithiques, fortement dopés avec des molécules actives, dans le cadre de la réalisation de limiteurs optiques performants dans le visible et dans l infrarouge.La mise au point de procédés et de matrices sol-gel compatibles avec divers types de chromophores a tout d abord été effectuée. Une investigation des paramètres expérimentaux et de la nature des précurseurs influençant la microstructure des matériaux a été réalisée, ainsi que la mise au point de méthodes de gélification accélérée capables de piéger efficacement les chromophores dans les matrices sol-gel même à de très hautes concentrations.Le dopage des matrices obtenues avec différents chromophores pour la limitation optique dans le visible et dans l infrarouge s en est suivi, avec une étude de l impact des matrices sur les propriétés optiques des dopants. L évaluation des performances en limitation a révélé les performances exceptionnelles des systèmes étudiés dans le visible, et des résultats prometteurs pour l infrarouge.Enfin, la synthèse de nanoparticules d or isotropes et anisotropes et leur incorporation dans les matériaux préparés a permis de mettre en évidence des effets d exaltation importants sur les propriétés non-linéaires des chromophores au sein des matrices sol-gel et permettent d améliorer les performances en limitation de manière considérable.Sol-gel chemistry is a potent approach for the realization of optical materials, and enables chromophores incorporation in materials making the soft process a gateway for many applications. In this work, we focused on monolithic sol-gel materials, heavily doped with optically active chromophores for the realization of solid-sate optical power limiting devices in the visible and near-infrared range.The elaboration and optimization of compatibles sol-gel matrices with those chromophores was the first step. An investigation of the different synthesis parameters and the nature of the precursors on the materials nanostructure were done, together with the creation of high speed gelation processes to enable the incorporation of very high chromophores contents.Using these approaches, the preparation of highly doped materials for optical power limiting in the visible and the near infrared range was successful, and the impact of the matrices on chromophores properties was studied. Evaluation of optical limiting properties of these materials revealed exceptional performance in the visible range and promising results for the NIR range.Finally, isotropic and anisotropic gold spheres were prepared and incorporated inside the materials. The resulting composites showed enhancements of the non-linear properties of the chromophores inside the matrix, and dramatic improvement of the optical power limiting efficiency was achieved.LYON-ENS Sciences (693872304) / SudocSudocFranceF

Chromophores à absorption multiphotonique pour l'imagerie et la photothérapie dynamique (synthèse, vectorisation, greffage sur nanoparticules d'or et propriétés spectroscopiques)

La thérapie photodynamique (PDT) est une méthode thérapeutique qui permet un ciblage spécifique de lésions par irradiation lumineuse localisée de photosensibilisateurs. L utilisation d une excitation biphotonique pourrait accroître son intérêt en augmentant sa profondeur de pénétration dans les tissus et en confinant son activité au point focal d un laser. Cependant, peu de chromophores actifs à deux photons ont été optimisés pour des applications biologique, car ils possèdent généralement de longues chaînes conjuguées qui les rendent très hydrophobes. Le recours à un vecteur nanométrique tel que les nanoparticules d or, capable de se concentrer dans les tumeurs, pourrait être une stratégie intéressante; d autant plus que celles ci possèdent aussi des propriétés optiques susceptibles d influencer la spectroscopie de chromophores placés à leur voisinage.Photodynamic therapy (PDT) is a therapeutic method which allows the specific targeting of lesions by the localized irradiation of photosensitizers. Biphotonic excitation should improve this method by increasing its penetration depth in biological tissues and restricting strictly its activity at the focal point of a laser. However, few biphotonic dyes has been optimized for biological applications because it are generally constituted by extended pi-conjugated chains which make them very hydrophobic. Nanometric drug delivery agents should be of great interest to tackle this problem thanks to their preferential accumulation in tumors. Gold nanoparticles are still more interesting because they possess intrinsic optical properties which may influence the efficiency of photosensitizers and imaging agents at their vicinity.LYON-ENS Sciences (693872304) / SudocSudocFranceF

Conjugués polymère-chromophores biphotoniques greffés sur des nanoparticules d'or comme sondes fluorescentes pour la bioimagerie et la photothérapie dynamique

La photothérapie dynamique (PTD) est un traitement alternatif du cancer qui nécessite l utilisation de chromophores (photosensibilisateurs) capables d induire la mort cellulaire suite à une irradiation lumineuse. Les nanoparticles d or (AuNP), grâce à leur phénomène de résonance plasmon localisée, peuvent exalter les propriétés photophysiques des chromophores localisés à leur surface. L utilisation d une excitation biphotonique, dans le proche infrarouge, peut être utilisée pour améliorer l action thérapeutique (PTD) ou diagnostique (imagerie de fluorescence) des chromophores en augmentant la profondeur de pénétration dans les tissus et la résolution tridimensionnelle de la microscopie biphotonique.Lors de ce travail, l élaboration de nouvelles nanoparticules hybrides est proposée, présentant des applications potentielles en bioimagerie (sondes brillantes) et comme photosensibilisateurs pour la PTD. Ces nanoparticules sont composées d un cœur d or sur lequel sont greffés des conjugués polymère-chromophores biphotoniques. La stratégie de synthèse a consisté à: i) synthétiser des conjugués polymère-chromophores biphotoniques solubles dans l eau; ii) les greffer de manière orientée à la surface des AuNP. La synthèse des conjugués polymère-chromophores hydrosolubles on été synthétisés via le couplage efficace de chromophores hydrophobes en position latérale des copolymères P(NAM-co-NAS) bien-définis, obtenus par la techniques de polymérisation radicalaire contrôlée RAFT. Cette stratégie permet le contrôle à la fois de la longueur des chaînes polymère formées (2000 g.mol-1 < Mn plus < 37 000 g.mol-1) et du nombre de chromophores couplés par chaîne (de 1 à 21). Le greffage orienté de ces conjugués à la surface des AuNP a été mis en évidence (TEM, ATG) et les densités de greffage se sont avérées élevées (~0.5chaîne/nm ). Un des rôles de la chaîne polymère étant de contrôler la distance entre les chromophores et la surface des AuNP. Il a été mis en évidence que l augmentation de la longueur de chaine des conjugués induisait, outre une augmentation de la couronne greffée (par MET) sur les AuNP, une augmentation de l émission de fluorescence de ces conjugués polymère-chromophores. Enfin, les propriétés biologiques des conjugués avant et après greffage sur les AuNP ont été évaluées in cellulo, mettant en valeur leur potentiel pour des applications thérapeutiques et diagnostiques.Photodynamic therapy (PDT) is an alternative treatment of cancer requiring the use of chromophore molecules (photosensitizers), which can induce cell death after light excitation. Gold nanoparticles (AuNP), exhibiting localized Surface Plasmon Resonance, can enhance the photophysical response of chromophores located in their vicinity, and thus improve their therapeutic action. Moreover, the use of highly localized two-photon chromophores (photosensitizers and fluorophores), capable to undergo a localized excitation by light in the Near InfraRed region, should increase the penetration depth into tissues, thus improve the treatment efficiency (by PDT) and the imaging (by fluorescence microscopy) of cancer tissues.In this work, we describe the elaboration of water-soluble hybrid nano-objects for PDT and fluorescence bioimaging applications, composed of two-photon chromophore-polymer conjugates grafted onto gold nanoparticles. In order to obtain these nano-objects we follow a multistep strategy: i) the synthesis of a well-defined water-soluble chromophore-polymer conjugates; ii) the end-group oriented grafting of chromophore-polymer conjugates onto 20 nm AuNP. The coupling of hydrophobic two-photon chromophores on linear water-soluble copolymer chains (poly(N-acryloylmorpholine-co-N-acryloxysuccinimide)), obtained by controlled/living RAFT polymerization, resulted in well-defined water-soluble chromophore-polymer conjugates, with different polymer lengths (2000 g.mol-1 < Mn < 37 000 g.mol-1) and architectures (random or block), and a controlled number of chromophores per chain (varying between 1 and 21). Their grafting onto 20 nm AuNP gave water-soluble hybrid nano-objects with high grafting densities (~0.5 chains/nm ). The role of the polymer chain being to tune the distance between chromophores and AuNP surface, we have evidenced the increase in the polymer corona thickness of grafted AuNP (estimated by TEM) with the increasing polymer Mn, corroborating with the corresponding distance-dependent fluorescence properties of those. Finally, the in cellulo biological properties of two-photon chromophore-polymer conjugates, before and after grafting onto AuNP, have been investigated, highlighting their potential for two-photon bioimaging and PDT applications.VILLEURBANNE-DOC'INSA-Bib. elec. (692669901) / SudocSudocFranceF

Fast Prototyping of Silica Glass Microfluidic Chips: The Sol-Gel Route

International audienceA combination of material, patterning, and sealing method is introduced to replicate and assemble monolithic microfluidic chips made of hybrid silica glass (HSG). First, it is shown how to prepare sols suited to the replication of complex geometries out of range of conventional etching methods. Second, it is shown how to tailor the surface properties of HSG devices. The performances and the simplicity of this fast prototyping method are demonstrated using quantitative mechanical, optical, and physicochemical characterization techniques and benchmark microfluidic experiments. Finally, the high potential of HSG microfluidics to oil-recovery and chemistry applications in benchmark experiments on crude oils is established

Beyond the Concentration Limitation in the Synthesis of Nanobipyramids and Other Pentatwinned Gold Nanostructures

International audienc