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121.
Karima Relizani Lucía Echevarría Faouzi Zarrouki Ccile Gastaldi Chloe Dambrune Philippine Aupy Adrian Haeberli Marek Komisarski Thomas Tensorer Thibaut Larcher Fedor Svinartchouk Cyrille Vaillend Luis Garcia Aurlie Goyenvalle 《Nucleic acids research》2022,50(1):17
Tricyclo-DNA (tcDNA) is a conformationally constrained oligonucleotide analog that has demonstrated great therapeutic potential as antisense oligonucleotide (ASO) for several diseases. Like most ASOs in clinical development, tcDNA were modified with phosphorothioate (PS) backbone for therapeutic purposes in order to improve their biodistribution by enhancing association with plasma and cell protein. Despite the advantageous protein binding properties, systemic delivery of PS-ASO remains limited and PS modifications can result in dose limiting toxicities in the clinic. Improving extra-hepatic delivery of ASO is highly desirable for the treatment of a variety of diseases including neuromuscular disorders such as Duchenne muscular dystrophy. We hypothesized that conjugation of palmitic acid to tcDNA could facilitate the delivery of the ASO from the bloodstream to the interstitium of the muscle tissues. We demonstrate here that palmitic acid conjugation enhances the potency of tcDNA-ASO in skeletal and cardiac muscles, leading to functional improvement in dystrophic mice with significantly reduced dose of administered ASO. Interestingly, palmitic acid-conjugated tcDNA with a full phosphodiester backbone proved effective with a particularly encouraging safety profile, offering new perspectives for the clinical development of PS-free tcDNA-ASO for neuromuscular diseases. 相似文献
122.
Serena Shunmugam Christophe-Sbastien Arnold Sheena Dass Nicholas J. Katris Cyrille Y. Bott 《PLoS pathogens》2022,18(3)
Apicomplexa are obligate intracellular parasites responsible for major human infectious diseases such as toxoplasmosis and malaria, which pose social and economic burdens around the world. To survive and propagate, these parasites need to acquire a significant number of essential biomolecules from their hosts. Among these biomolecules, lipids are a key metabolite required for parasite membrane biogenesis, signaling events, and energy storage. Parasites can either scavenge lipids from their host or synthesize them de novo in a relict plastid, the apicoplast. During their complex life cycle (sexual/asexual/dormant), Apicomplexa infect a large variety of cells and their metabolic flexibility allows them to adapt to different host environments such as low/high fat content or low/high sugar levels. In this review, we discuss the role of lipids in Apicomplexa parasites and summarize recent findings on the metabolic mechanisms in host nutrient adaptation. 相似文献
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124.
Bioclimatic model of tree radial growth: application to the French Mediterranean Aleppo pine forests
Cyrille B. K. Rathgeber Laurent Misson Antoine Nicault Joël Guiot 《Trees - Structure and Function》2005,19(2):162-176
The potential effects of global changes on forests are of increasing concern. Dendrochronology, which deals with long-term records of tree growth under natural environmental conditions, can be used to evaluate the impact of climatic change on forest productivity. However, assessment of climatic change impacts must be supported by accurate and reliable models of the relationships between climate and tree growth. In this study, a bioclimatic model is used to explore the relationships between tree radial growth and bioclimatic variables closely related to the biological functioning of a tree. This model is at an intermediate level of complexity between purely empirical and process-based models. The method is illustrated with data for 21 Aleppo pine (Pinus halepensis Mill.) stands grown under a Mediterranean climate in south-east France. The results show that Aleppo pine growth is mainly controlled by soil water availability during the growing season. The bioclimatic variable which best expresses the observed inter-annual tree growth variations is the actual evapotranspiration (AET). Four parameters were adjusted to simulate dendrochronological data: the soil water capacity, the wilting point, the minimum temperature for photosynthesis, and the end of the growing season. The bioclimatic model gives better results than the standard response function and provides better insight into the functional processes involved in tree growth. The convincing results obtained by the bioclimatic model as well as the limited numbers of parameters it requires demonstrate the feasibility of using it to explore future climatic change impacts on Aleppo pine forests. 相似文献
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126.
Célestine M. Atyame Julien Cattel Cyrille Lebon Olivier Flores Jean-Sébastien Dehecq Mylène Weill Louis Clément Gouagna Pablo Tortosa 《PloS one》2015,10(3)
In mosquitoes, the maternally inherited bacterial Wolbachia induce a form of embryonic lethality called cytoplasmic incompatibility (CI). This property can be used to reduce the density of mosquito field populations through inundative releases of incompatible males in order to sterilize females (Incompatible Insect Technique, or IIT, strategy). We have previously constructed the LR[wPip(Is)] line representing a good candidate for controlling field populations of the Culex quinquefasciatus mosquito in the islands of the south-western Indian Ocean. The main purpose of the present study was to fill the gap between laboratory experiments and field implementation, i.e. assessing mating competitiveness of these incompatible males under semi-field conditions. In a first set of experiments, we analyzed crossing relationships between LR[wPip(Is)] males and La Réunion field females collected as larvae in 19 distinct localities throughout the island. This investigation revealed total embryonic mortality, confirming the strong sterilizing capacity of LR[wPip(Is)] males. Subsequently, mating competitiveness of LR[wPip(Is)] males was assessed under semi-field conditions in the presence of field males and females from La Réunion. Confrontations were carried out in April and December using different ratios of LR[wPip(Is)] to field males. The results indicated that the LR[wPip(Is)] males successfully compete with field males in mating with field females, displaying even higher competitiveness than field males in April. Our results support the implementation of small-scale field tests in order to assess the feasibility of IIT against Cx. quinquefasciatus in the islands of southwestern Indian Ocean where this mosquito species is a proven competent vector for human pathogens. 相似文献
127.
Marianne Parent Ariane Boudier Julien Perrin Claude Vigneron Philippe Maincent Nicolas Violle Jean-Fran?ois Bisson Isabelle Lartaud Fran?ois Dupuis 《PloS one》2015,10(12)
Treatment of stroke, especially during the first hours or days, is still lacking. S-nitrosoglutathione (GSNO), a cerebroprotective agent with short life time, may help if administered early with a sustain delivery while avoiding intensive reduction in blood pressure. We developed in situ forming implants (biocompatible biodegradable copolymer) and microparticles (same polymer and solvent emulsified with an external oily phase) of GSNO to lengthen its effects and allow cerebroprotection after a single subcutaneous administration to Wistar rats. Arterial pressure was recorded for 3 days (telemetry, n = 14), whole-blood platelet aggregation up to 13 days (aggregometry, n = 58), and neurological score, cerebral infarct size and edema volume for 2 days after obstruction of the middle cerebral artery by autologous blood clots (n = 30). GSNO-loaded formulations (30 mg/kg) induced a slighter and longer hypotension (-10 vs. -56 ± 6 mmHg mean arterial pressure, 18 h vs. 40 min) than free GSNO at the same dose. The change in pulse pressure (-50%) lasted even up to 42 h for microparticles. GSNO-loaded formulations (30 mg/kg) prevented the transient 24 h hyper-aggregability observed with free GSNO and 7.5 mg/kg-loaded formulations. When injected 2 h after stroke, GSNO-loaded microparticles (30 mg/kg) reduced neurological score at 24 (-62%) and 48 h (-75%) vs. empty microparticles and free GSNO 7.5 mg/kg and, compared to free GSNO, divided infarct size by 10 and edema volume by 8 at 48 h. Corresponding implants reduced infarct size and edema volume by 2.5 to 3 times. The longer (at least 2 days) but slight effects on arterial pressures show sustained delivery of GSNO-loaded formulations (30 mg/kg), which prevent transient platelet hyper-responsiveness and afford cerebroprotection against the consequences of stroke. In conclusion, in situ GSNO-loaded formulations are promising candidates for the treatment of stroke. 相似文献
128.
Ga?l Mourembou Florence Fenollar Jean Bernard Lekana-Douki Angelique Ndjoyi Mbiguino Sydney Maghendji Nzondo Pierre Blaise Matsiegui Rella Zoleko Manego Cyrille Herve Bile Ehounoud Fadi Bittar Didier Raoult Oleg Mediannikov 《PLoS neglected tropical diseases》2015,9(10)
Background
Like other tropical African countries, Gabon is afflicted by many parasitic diseases, including filariases such as loiasis and mansonellosis. This study aimed to assess the prevalence of these two filarial diseases in febrile and afebrile children using quantitative real-time PCR and standard PCR assays coupled with sequencing.Methodology/Principal Findings
DNA from blood specimens of 1,418 Gabonese children (1,258 febrile and 160 afebrile) were analyzed. Overall, filarial DNA was detected in 95 (6.7%) children, including 67 positive for M. perstans (4.7%), which was the most common. M. perstans was detected in 61/1,258 febrile children (4.8%) and 6/160 afebrile children (3.8%, P = 0.6). Its prevalence increased statistically with age: 3.5%, 7.7% and 10.6% in children aged ≤5, 6–10 and 11–15 years, respectively. M. perstans prevalence was significantly higher in Koulamoutou and Lastourville (12% and 10.5%, respectively) than in Franceville and Fougamou (2.6% and 2.4%, respectively). Loa loa was detected in seven febrile children including one co-infection with M. perstans. Finally, 21 filarial DNA positive were negative for M. perstans and Loa loa, but ITS sequencing could be performed for 12 and allowed the identification of a potential new species of Mansonella provisionally called “DEUX”. Mansonella sp. “DEUX” was detected only in febrile children.Conclusions/Significance
Further study should be performed to characterize Mansonella sp. “DEUX” and evaluate the clinical significance of mansonellosis in humans. 相似文献129.
A global meta‐analysis of the relative extent of intraspecific trait variation in plant communities
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Andrew Siefert Cyrille Violle Loïc Chalmandrier Cécile H. Albert Adrien Taudiere Alex Fajardo Lonnie W. Aarssen Christopher Baraloto Marcos B. Carlucci Marcus V. Cianciaruso Vinícius de L. Dantas Francesco de Bello Leandro D. S. Duarte Carlos R. Fonseca Grégoire T. Freschet Stéphanie Gaucherand Nicolas Gross Kouki Hikosaka Benjamin Jackson Vincent Jung Chiho Kamiyama Masatoshi Katabuchi Steven W. Kembel Emilie Kichenin Nathan J. B. Kraft Anna Lagerström Yoann Le Bagousse‐Pinguet Yuanzhi Li Norman Mason Julie Messier Tohru Nakashizuka Jacob McC. Overton Duane A. Peltzer I. M. Pérez‐Ramos Valério D. Pillar Honor C. Prentice Sarah Richardson Takehiro Sasaki Brandon S. Schamp Christian Schöb Bill Shipley Maja Sundqvist Martin T. Sykes Marie Vandewalle David A. Wardle 《Ecology letters》2015,18(12):1406-1419
Recent studies have shown that accounting for intraspecific trait variation (ITV) may better address major questions in community ecology. However, a general picture of the relative extent of ITV compared to interspecific trait variation in plant communities is still missing. Here, we conducted a meta‐analysis of the relative extent of ITV within and among plant communities worldwide, using a data set encompassing 629 communities (plots) and 36 functional traits. Overall, ITV accounted for 25% of the total trait variation within communities and 32% of the total trait variation among communities on average. The relative extent of ITV tended to be greater for whole‐plant (e.g. plant height) vs. organ‐level traits and for leaf chemical (e.g. leaf N and P concentration) vs. leaf morphological (e.g. leaf area and thickness) traits. The relative amount of ITV decreased with increasing species richness and spatial extent, but did not vary with plant growth form or climate. These results highlight global patterns in the relative importance of ITV in plant communities, providing practical guidelines for when researchers should include ITV in trait‐based community and ecosystem studies. 相似文献
130.
Audrey Salles Cyrille Billaudeau Arnauld Sergé Anne-Marie Bernard Marie-Claire Phélipot Nicolas Bertaux Mathieu Fallet Pierre Grenot Didier Marguet Hai-Tao He Yannick Hamon 《PLoS computational biology》2013,9(9)
We introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells. 相似文献