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131.
Pranav Kumar Robert Lodge Frédéric Raymond Jean‐François Ritt Pascal Jalaguier Jacques Corbeil Marc Ouellette Michel J. Tremblay 《Molecular microbiology》2013,89(3):565-582
Drug resistance is a major public health challenge in leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV‐1 co‐infections. We have delineated the mechanism of cell death induced by the HIV‐1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to further study Nelfinavir–Leishmania interactions, we selected Nelfinavir‐resistant axenic amastigotes in vitro and characterized them. RNA expression profiling analyses and comparative genomic hybridizations of closely related Leishmania species were used as a screening tool to compare Nelfinavir‐resistant and ‐sensitive parasites in order to identify candidate genes involved in drug resistance. Microarray analyses of Nelfinavir‐resistant and ‐sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters. Transporter assays using radiolabelled Nelfinavir suggest a greater drug accumulation in the resistant parasites and in a time‐dependent manner. Furthermore, high‐resolution electron microscopy and measurements of intracellular polyphosphate levels showed an increased number of cytoplasmic vesicular compartments known as acidocalcisomes in Nelfinavir‐resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in drug‐induced intracellular vesicles. 相似文献
132.
Jena R. Hickey Janet Nackoney Nathan P. Nibbelink Stephen Blake Aime Bonyenge Sally Coxe Jef Dupain Maurice Emetshu Takeshi Furuichi Falk Grossmann Patrick Guislain John Hart Chie Hashimoto Bernard Ikembelo Omari Ilambu Bila-Isia Inogwabini Innocent Liengola Albert Lotana Lokasola Alain Lushimba Fiona Maisels Joel Masselink Valentin Mbenzo Norbert Mbangia Mulavwa Pascal Naky Nicolas Mwanza Ndunda Pele Nkumu Valentin Omasombo Gay Edwards Reinartz Robert Rose Tetsuya Sakamaki Samantha Strindberg Hiroyuki Takemoto Ashley Vosper Hjalmar S. Kühl 《Biodiversity and Conservation》2013,22(13-14):3085-3104
Habitat loss and hunting threaten bonobos (Pan paniscus), Endangered (IUCN) great apes endemic to lowland rainforests of the Democratic Republic of Congo. Conservation planning requires a current, data-driven, rangewide map of probable bonobo distribution and an understanding of key attributes of areas used by bonobos. We present a rangewide suitability model for bonobos based on a maximum entropy algorithm in which data associated with locations of bonobo nests helped predict suitable conditions across the species’ entire range. We systematically evaluated available biotic and abiotic factors, including a bonobo-specific forest fragmentation layer (forest edge density), and produced a final model revealing the importance of simple threat-based factors in a data poor environment. We confronted the issue of survey bias in presence-only models and devised a novel evaluation approach applicable to other taxa by comparing models built with data from geographically distinct sub-regions that had higher survey effort. The model’s classification accuracy was high (AUC = 0.82). Distance from agriculture and forest edge density best predicted bonobo occurrence with bonobo nests more likely to occur farther from agriculture and in areas of lower edge density. These results suggest that bonobos either avoid areas of higher human activity, fragmented forests, or both, and that humans reduce the effective habitat of bonobos. The model results contribute to an increased understanding of threats to bonobo populations, as well as help identify priority areas for future surveys and determine core bonobo protection areas. 相似文献
133.
BackgroundNew CZT cameras provide an increased spatial resolution and sensitivity. The tomographic acquisition “in list mode” allows the evaluation of the left ventricular function using 8–16 intervals per cycle with an increased spatial resolution. However, the impact of temporal sampling on evaluation of the contractile function remains uncertain.Method99mTc-sestamibi SPECT studies were acquired in 99 consecutive patients (70 men, 29 women) using an ultrafast CZT Camera (D-Spectrum, Spectrum Dynamics) and processed using both 8- and 16-interval (int). All patients underwent a stress (2 MBq/kg)-rest (6 MBq/kg) single day (stop condition: 700 KCTS within a myocardial VOI). Left ventricular function was assessed using QGS®. Perfusion was analyzed using QPS® and quantified using Summed Stress Score (SSS), Summed Rest Score (SRS) and Summed Difference Score (SDS) (17 segments model) and the extent of perfusion defects (% of LV).ResultsEight intervals gating overestimated the end-systolic volumes (ESV) and underestimated the left ventricular ejection fraction (LVEF) compared to 16 intervals (respectively for eight and 16 intervals: at rest [VTS: 45 ± 25 mL vs 41 ± 24 mL, P < 0.0001, LVEF: 53 ± 10% vs 59 ± 10%, P < 0.0001], and post-stress [VTS: 43 ± 24. mL vs 39 ± 24 mL, P < 0.0001; LVEF: 58 ± 10% vs 61 ± 11%, P < 0.0001]). However, it was not found significant differences between end diastolic volumes (EDV) (at rest: EDV: 98 ± 33 mL vs 97 ± 33 mL, P = NS; and post-stress: EDV: 98 ± 33 ml vs 99 ± 34 mL, P = NS). Parameters of left ventricular function were consistent between eight and 16 intervals (EDV: CCC = 0.99, ESV: CCC = 0.98, LVEF: CCC = 0.92, P < 0.0001). Correlation could not be evidenced between the extent of perfusion defect and the difference between eight and 16 intervals for the different parameters of left ventricular function both at rest and post-stress.ConclusionIn our study, comparison between eight and 16 intervals showed an overestimation of the ESV and an underestimation of LVEF, without correlation with perfusion abnormalities. The estimation of LVEF on CZT camera should take into account the chosen temporal sampling. 相似文献
134.
Charlotte Ndiribe Loïc Pellissier Silvia Antonelli Anne Dubuis Julien Pottier Pascal Vittoz Nicolas Salamin 《Ecology and evolution》2013,3(15):4925-4939
The trend of closely related taxa to retain similar environmental preferences mediated by inherited traits suggests that several patterns observed at the community scale originate from longer evolutionary processes. While the effects of phylogenetic relatedness have been previously studied within a single genus or family, lineage‐specific effects on the ecological processes governing community assembly have rarely been studied for entire communities or flora. Here, we measured how community phylogenetic structure varies across a wide elevation gradient for plant lineages represented by 35 families, using a co‐occurrence index and net relatedness index (NRI). We propose a framework that analyses each lineage separately and reveals the trend of ecological assembly at tree nodes. We found prevailing phylogenetic clustering for more ancient nodes and overdispersion in more recent tree nodes. Closely related species may thus rapidly evolve new environmental tolerances to radiate into distinct communities, while older lineages likely retain inherent environmental tolerances to occupy communities in similar environments, either through efficient dispersal mechanisms or the exclusion of older lineages with more divergent environmental tolerances. Our study illustrates the importance of disentangling the patterns of community assembly among lineages to better interpret the ecological role of traits. It also sheds light on studies reporting absence of phylogenetic signal, and opens new perspectives on the analysis of niche and trait conservatism across lineages. 相似文献
135.
A sudden transition in a system from an inanimate state to the living state—defined on the basis of present day living organisms—would constitute a highly unlikely event hardly predictable from physical laws. From this uncontroversial idea, a self-consistent representation of the origin of life process is built up, which is based on the possibility of a series of intermediate stages. This approach requires a particular kind of stability for these stages—dynamic kinetic stability (DKS)—which is not usually observed in regular chemistry, and which is reflected in the persistence of entities capable of self-reproduction. The necessary connection of this kinetic behaviour with far-from-equilibrium thermodynamic conditions is emphasized and this leads to an evolutionary view for the origin of life in which multiplying entities must be associated with the dissipation of free energy. Any kind of entity involved in this process has to pay the energetic cost of irreversibility, but, by doing so, the contingent emergence of new functions is made feasible. The consequences of these views on the studies of processes by which life can emerge are inferred. 相似文献
136.
Pascal Hingamp Nigel Grimsley Silvia G Acinas Camille Clerissi Lucie Subirana Julie Poulain Isabel Ferrera Hugo Sarmento Emilie Villar Gipsi Lima-Mendez Karoline Faust Shinichi Sunagawa Jean-Michel Claverie Hervé Moreau Yves Desdevises Peer Bork Jeroen Raes Colomban de Vargas Eric Karsenti Stefanie Kandels-Lewis Olivier Jaillon Fabrice Not Stéphane Pesant Patrick Wincker Hiroyuki Ogata 《The ISME journal》2013,7(9):1678-1695
Nucleo-cytoplasmic large DNA viruses (NCLDVs) constitute a group of eukaryotic viruses that can have crucial ecological roles in the sea by accelerating the turnover of their unicellular hosts or by causing diseases in animals. To better characterize the diversity, abundance and biogeography of marine NCLDVs, we analyzed 17 metagenomes derived from microbial samples (0.2–1.6 μm size range) collected during the Tara Oceans Expedition. The sample set includes ecosystems under-represented in previous studies, such as the Arabian Sea oxygen minimum zone (OMZ) and Indian Ocean lagoons. By combining computationally derived relative abundance and direct prokaryote cell counts, the abundance of NCLDVs was found to be in the order of 104–105 genomes ml−1 for the samples from the photic zone and 102–103 genomes ml−1 for the OMZ. The Megaviridae and Phycodnaviridae dominated the NCLDV populations in the metagenomes, although most of the reads classified in these families showed large divergence from known viral genomes. Our taxon co-occurrence analysis revealed a potential association between viruses of the Megaviridae family and eukaryotes related to oomycetes. In support of this predicted association, we identified six cases of lateral gene transfer between Megaviridae and oomycetes. Our results suggest that marine NCLDVs probably outnumber eukaryotic organisms in the photic layer (per given water mass) and that metagenomic sequence analyses promise to shed new light on the biodiversity of marine viruses and their interactions with potential hosts. 相似文献
137.
Markus Ernstberger Pascal Boeswetter Tobias Baselt Frank Ebert Fabiola Basan Hanno Steinke Niels Hammer Ronny Grunert Peter Hartmann 《Journal of biophotonics》2013,6(4):310-313
Thin slices of human tissues are characterized concerning reflection and transmission in a wavelength range from 400 to 1700 nm. The results are primarily useful to find a wavelength for the detection of subjacent blood vessels during surgical procedures, especially neurological surgery. The measurements have been conducted using a customized measuring station, utilizing two halogen bulb lamps and two spectrometers. This paper focuses on creating a data base with the optical properties of artery, brain, bone, nasal mucosa, and nerve. The spectral distributions are compared among each other, similarities and differences are pointed out. Each tissue has got unique spectral characteristics, whereas typical absorption bands can be found in the overall tissues, especially hemoglobin and water absorption bands. The reflectivity maxima are typically located in the red or near‐infrared. All the transmission maxima are located between 1075 nm and 1100 nm. The measurements have been conducted at the Institute of Anatomy at the University of Leipzig. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
138.
Sophie Pinel Jihane Mriouah Marc Vandamme Alicia Chateau Fran?ois Plénat Eric Guérin Luc Taillandier Valérie Bernier-Chastagner Jean-Louis Merlin Pascal Chastagner 《PloS one》2013,8(7)
In high-grade gliomas, the identification of patients that could benefit from EGFR inhibitors remains a challenge, hindering the use of these agents. Using xenografts models, we evaluated the antitumor effect of the combined treatment “gefitinib + radiotherapy” and aimed to identify the profile of responsive tumors. Expression of phosphorylated proteins involved in the EGFR-dependent signaling pathways was analyzed in 10 glioma models. We focused on three models of anaplastic oligodendrogliomas (TCG2, TCG3 and TCG4) harboring high levels of phospho-EGFR, phospho-AKT and phospho-MEK1. They were treated with gefitinib (GEF 75 mg/kg/day x 5 days/week, for 2 weeks) and/or fractionated radiotherapy (RT: 5x2Gy/week for 2 weeks). Our results showed that GEF and/or RT induced significant tumor growth delays. However, only the TCG3 xenografts were highly responsive to the combination GEF+RT, with ∼50% of tumor cure. Phosphoproteins analysis five days after treatment onset demonstrated in TCG3 xenografts, but not in TCG2 model, that the EGFR-dependent pathways were inhibited after GEF treatment. Moreover, TCG3-bearing mice receiving GEF monotherapy exhibited a transient beneficial therapeutic response, rapidly followed by tumor regrowth, along with a major vascular remodeling. Taken together, our data evoked an “EGFR-addictive” behavior for TCG3 tumors. This study confirms that combination of gefitinib with fractionated irradiation could be a potent therapeutic strategy for anaplastic oligodendrogliomas harboring EGFR abnormalities but this treatment seems mainly beneficial for “EGFR-addictive” tumors. Unfortunately, neither the usual molecular markers (EGFR amplification, PTEN loss) nor the basal overexpression of phosphoproteins were useful to distinguish this responsive tumor. Evaluating the impact of TKIs on the EGFR-dependent pathways during the treatment might be more relevant, and requires further validation. 相似文献
139.
Two methods of measuring primary production, modulated fluorimetry (PAM) and the traditional carbon incorporation method (13C), were compared in four phytoplankton species, two diatoms (Pseudo-nitzschia pungens and Asterionellopsis glacialis), and two dinoflagellates (Heterocapsa sp and Karenia mikimotoï), under N (nitrogen), P (phosphorus) and Si (silicon) limited semi-continuous culture. N and Si-limited cultures showed relatively high quantum efficiency of the PSII (Fv/Fm) values, confirming that Fv/Fm is not a good proxy for nutrient stress in balanced systems, whereas P limitation had a drastic effect on many physiological parameters. In all species, the physiological capacity of phytoplankton cells to acclimate to nutrient limitations led to changes in the cellular biochemical composition and the structure of the photosynthetic apparatus. The observed physiological responses were species and nutrient specific. The values of the chlorophyll-specific absorption cross section (a*) increased with nutrient limitation due to package effect, while the carbon/Chl a ratio was higher under N and P limitations. In diatoms, Si limitation did not affect photosynthesis confirming the uncoupling between Si and carbon metabolisms. In all four species and under all treatments, significant relationships were found between photosynthetic activities, ETRChl (electron transport rate) and PChl (carbon fixation rate) estimated using PAM measurements and 13C incorporation, showing that the fluorescence technique can reliably be used to estimate carbon fixation by phytoplankton. The relationship between ETRChl and PChl can be described by the shape and the slope of the curve (ΦC.e). Linear relationships were found for dinoflagellates and P. pungens under all treatments. A decrease in ΦC.e was observed under N and P limitation probably due to structural damage to the photosynthetic apparatus. A. glacialis showed a logarithmic relationship in N and P limited conditions, due to the alternative electron flow which takes place to optimise photosynthetic performances under high light and/or nutrient stress. 相似文献
140.
Hammadoum A. Sango Jean Testa Nicolas Meda Benjamin Contrand Mamadou S. Traoré Pascal Staccini Emmanuel Lagarde 《PloS one》2016,11(2)