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201.
Marie-Paule?VassonEmail author Marie-Chantal?Farges Nicolas?Goncalves-Mendes Jérémie?Talvas Josep?Ribalta Brigitte?Winklhofer-Roob Edmond?Rock Adrien?Rossary 《Immunity & ageing : I & A》2013,10(1):38
Background
As the European population is getting older, there is growing need in scientific data on how to achieve healthy and successful aging. A decline in immune function with age is unanimously supported by many epidemiological and clinical observations, with a decrease in T-cell mediated function encompassing a large part of this alteration. In the EU-funded VITAGE project, the effects of aging on biomarkers of immune status are being studied in three European countries. According to strict inclusion/exclusion criteria, a cohort of 300 healthy male non-smoking 20–75 years old volunteers were enrolled in France (n?=?99), Spain (n?=?100) and Austria (n?=?101). In each country, the volunteers were classified as a function of age (one age group per decade). Biomarkers of immune status were determined including delayed-type hypersensitivity tests, measurement of lymphocyte surface markers, and serum determinations of interleukin-2, complement fractions and immunoglobulins.Results
There were moderate differences in the biomarkers of immune status of the VITAGE study volunteers among the three European centres. The percentage of Natural Killer (NK) cells was 156% and 142% higher in Spain as compared to France and Austria, respectively (p?<?0.0001), and this increase was observed at any age group above 30 years. Comparison between age-groups showed that in Spain, but not in France or Austria, older individuals had significantly a lower B lymphocyte distribution and conversely, a higher NK cell distribution. Moreover, the CD4/CD8 ratio was positively correlated with age in Austrian subjects (p?<?0.0001).Conclusion
Our results provide evidence of an increased NK cell distribution in the elderly, especially in the Spanish population. NK cell status may predict morbidity and mortality in the elderly, emphasizing the importance of innate as well as adaptive immunity in ensuring healthy longevity and cancer resistance, possibly in link with the Mediterranean diet.202.
Marusela?Oliveras-Salvá Anke?Van der Perren Nicolas?Casadei Stijn?Stroobants Silke?Nuber Rudi?D’Hooge Chris?Van den Haute Veerle?BaekelandtEmail author 《Molecular neurodegeneration》2013,8(1):44
Background
Alpha-synuclein is a key protein implicated in the pathogenesis of Parkinson's disease (PD). It is the main component of the Lewy bodies, a cardinal neuropathological feature in the disease. In addition, whole locus multiplications and point mutations in the gene coding for alpha-synuclein lead to autosomal dominant monogenic PD. Over the past decade, research on PD has impelled the development of new animal models based on alpha-synuclein. In this context, transgenic mouse lines have failed to reproduce several hallmarks of PD, especially the strong and progressive dopaminergic neurodegeneration over time that occurs in the patients. In contrast, viral vector-based models in rats and non-human primates display prominent, although highly variable, nigral dopaminergic neuron loss. However, the few studies available on viral vector-mediated overexpression of alpha-synuclein in mice report a weak neurodegenerative process and no clear Lewy body-like pathology. To address this issue, we performed a comprehensive comparative study of alpha-synuclein overexpression by means of recombinant adeno-associated viral vectors serotype 2/7 (rAAV2/7) at different doses in adult mouse substantia nigra.Results
We noted a significant and dose-dependent alpha-synucleinopathy over time upon nigral viral vector-mediated alpha-synuclein overexpression. We obtained a strong, progressive and dose-dependent loss of dopaminergic neurons in the substantia nigra, reaching a maximum of 82% after 8 weeks. This effect correlated with a reduction in tyrosine hydroxylase immunoreactivity in the striatum. Moreover, behavioural analysis revealed significant motor impairments from 12 weeks after injection on. In addition, we detected the presence of alpha-synuclein-positive aggregates in the remaining surviving neurons. When comparing wild-type to mutant A53T alpha-synuclein at the same vector dose, both induced a similar degree of cell death. These data were supported by a biochemical analysis that showed a net increase in soluble and insoluble alpha-synuclein expression over time to the same extent for both alpha-synuclein variants.Conclusions
In conclusion, our in vivo data provide evidence that strong and significant alpha-synuclein-induced neuropathology and progressive dopaminergic neurodegeneration can be achieved in mouse brain by means of rAAV2/7.203.
Ali Moukadem Alain Dieterlen Nicolas Hueber Christian Brandt 《Biomedical signal processing and control》2013,8(3):273-281
This paper presents a new module for heart sounds segmentation based on S-transform. The heart sounds segmentation process segments the PhonoCardioGram (PCG) signal into four parts: S1 (first heart sound), systole, S2 (second heart sound) and diastole. It can be considered one of the most important phases in the auto-analysis of PCG signals. The proposed segmentation module can be divided into three main blocks: localization of heart sounds, boundaries detection of the localized heart sounds and classification block to distinguish between S1 and S2. An original localization method of heart sounds are proposed in this study. The method named SSE calculates the Shannon energy of the local spectrum calculated by the S-transform for each sample of the heart sound signal. The second block contains a novel approach for the boundaries detection of S1 and S2. The energy concentrations of the S-transform of localized sounds are optimized by using a window width optimization algorithm. Then the SSE envelope is recalculated and a local adaptive threshold is applied to refine the estimated boundaries. To distinguish between S1 and S2, a feature extraction method based on the singular value decomposition (SVD) of the S-matrix is applied in this study. The proposed segmentation module is evaluated at each block according to a database of 80 sounds, including 40 sounds with cardiac pathologies. 相似文献
204.
Arbuscular mycorrhizal fungi (AMF) represent an ecologically relevant and evolutionarily intriguing group of land plant symbionts, which produce multinucleated spores and hyphae that are currently thought to have propagated clonally for over 500 million years. This long-term absence of sex in AMF is a puzzling evolutionary feature that has sparked scientific interest for some time, but a provoking explanation for their successful evolutionary history in the absence of an obvious sexual cycle is that these organisms may have cryptic sex, or a parasexual life cycle, allowing them to recombine alleles and compensate for deleterious mutations. Interestingly, the recent acquisition of large sequence data from many AMF species can finally allow this hypothesis to be tested more extensively. In this perspective, we highlight emerging evidence based on sequence data for the potential of AMF to have sexual reproduction, and propose a number of routes that could be taken to further explore the presence (or absence thereof) of sex in this poorly studied, yet highly relevant, fungal group. 相似文献
205.
Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 µg/kg/month) and Zol 1W (100 µg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn+/+ and Postn−/− (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn−/−. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn−/− and Postn+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn−/− vs Postn+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn−/− and Postn+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn−/−, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn−/− mice, zoledronate is not sufficient to induce bone necrosis. 相似文献
206.
Emmanuelle Dortel Félix Massiot-Granier Etienne Rivot Julien Million Jean-Pierre Hallier Eric Morize Jean-Marie Munaron Nicolas Bousquet Emmanuel Chassot 《PloS one》2013,8(4)
Age estimates, typically determined by counting periodic growth increments in calcified structures of vertebrates, are the basis of population dynamics models used for managing exploited or threatened species. In fisheries research, the use of otolith growth rings as an indicator of fish age has increased considerably in recent decades. However, otolith readings include various sources of uncertainty. Current ageing methods, which converts an average count of rings into age, only provide periodic age estimates in which the range of uncertainty is fully ignored. In this study, we describe a hierarchical model for estimating individual ages from repeated otolith readings. The model was developed within a Bayesian framework to explicitly represent the sources of uncertainty associated with age estimation, to allow for individual variations and to include knowledge on parameters from expertise. The performance of the proposed model was examined through simulations, and then it was coupled to a two-stanza somatic growth model to evaluate the impact of the age estimation method on the age composition of commercial fisheries catches. We illustrate our approach using the saggital otoliths of yellowfin tuna of the Indian Ocean collected through large-scale mark-recapture experiments. The simulation performance suggested that the ageing error model was able to estimate the ageing biases and provide accurate age estimates, regardless of the age of the fish. Coupled with the growth model, this approach appeared suitable for modeling the growth of Indian Ocean yellowfin and is consistent with findings of previous studies. The simulations showed that the choice of the ageing method can strongly affect growth estimates with subsequent implications for age-structured data used as inputs for population models. Finally, our modeling approach revealed particularly useful to reflect uncertainty around age estimates into the process of growth estimation and it can be applied to any study relying on age estimation. 相似文献
207.
Liselotte W. Wijsman Anton J. M. de Craen Stella Trompet Jacobijn Gussekloo David J. Stott Nicolas Rodondi Paul Welsh J. Wouter Jukema Rudi G. J. Westendorp Simon P. Mooijaart 《PloS one》2013,8(3)
Background
Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).Methods
Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.Results
Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.Conclusion
We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence. 相似文献208.
Nicolas Guillot Dmitrij Kollins Juan J. Badimon Detlef Schlondorff Randolph Hutter 《PloS one》2013,8(3)
Background
Intimal injury rapidly activates TGFβ and enhances vascular repair by the growth of endothelial (EC) and vascular smooth muscle cells (VSMC). The response to the TGFβ family of growth factors can be modified by BAMBI (BMP, Activin, Membrane Bound Inhibitor) acting as a non-signaling, competitive antagonist of TGFβ type I receptors such as ALK 1 and 5. In vivo the effect of BAMBI will depend on its cell-specific expression and of that of the ALK type receptors. We recently reported EC restricted BAMBI expression and genetic elimination of BAMBI resulting in an in vitro and in vivo phenotype characterized by endothelial activation and proliferation involving alternative pathway activation by TGFβ through ALK 1.Methodology/Principal Findings
To test the hypothesis that BAMBI modulates arterial response to injury via its effects on endothelial repair and arterial wall neovascularization we used a model of femoral arterial denudation injury in wild type (WT) and BAMBI−/− mice. Arterial response was evaluated at 2 and 4 weeks after luminal endothelial denudation of femoral arteries. The BAMBI−/− genotype mice showed accelerated luminal endothelial repair at 2 weeks and a highly unusual increase in arterial wall neovascularization compared to WT mice. The exuberant intimal and medial neovessel formation with BAMBI−/− genotype was also associated with significant red blood cell extravasation. The bleeding into the neointima at 2 weeks transiently increased it’s area in the BAMBI−/−genotype despite the faster luminal endothelial repair in this group. Vascular smooth muscle cells were decreased at 2 weeks in BAMBI−/− mice, but comparable to wild type at 4 weeks.Conclusions/Significance
The absence of BAMBI results in a highly unusual surge in arterial wall neovascularization that surprisingly mimiks features of intra-plaque hemorrhage of advanced atheroma in a mechanical injury model. This suggests important effects of BAMBI on arterial EC homeostasis that need to be further studied in a model of inflammatory atherosclerosis. 相似文献209.
Photoreceptor neurons (R cells) in the Drosophila eye define a map of visual space by connecting to targets in distinct layers of the optic lobe, with R1-6 cells connecting to the lamina (the first optic ganglion) and R7 and R8 cells connecting to the medulla (the second optic ganglion). Here, we show that Wengen (Wgn) directly binds Moesin (Moe) through a cytosolic membrane proximal domain and this interaction is important for mediating two distinct aspects of axonal targeting. First, we show that loss of wgn or moe function disrupts cell autonomous R8 axon targeting. Second, we report that wgn or moe mutants show defects in R2–R5 targeting that result from disruption of non-cell autonomous effects, which are secondary to the cell autonomous R8 phenotype. Thus, these studies reveal that the Wgn-Moe signaling cascade plays a key role in photoreceptor target field innervations through cell autonomous and non-cell autonomous mechanisms. 相似文献
210.
Controlling the prevalence of Escherichia coli O157 in cattle at the pre-harvest level is critical to reduce outbreaks of this pathogen in humans. Multilayers of factors including the environmental and bacterial factors modulate the colonization and persistence of E. coli O157 in cattle that serve as a reservoir of this pathogen. Here, we report animal factors contributing to the prevalence of E. coli O157 in cattle. We observe the lowest number of E. coli O157 in Brahman breed when compared with other crosses in an Angus-Brahman multibreed herd, and bulls excrete more E. coli O157 than steers in the pens where cattle were housed together. The presence of super-shedders, cattle excreting >105 CFU/rectal anal swab, increases the concentration of E. coli O157 in the pens; thereby super-shedders enhance transmission of this pathogen among cattle. Molecular subtyping analysis reveal only one subtype of E. coli O157 in the multibreed herd, indicating the variance in the levels of E. coli O157 in cattle is influenced by animal factors. Furthermore, strain tracking after relocation of the cattle to a commercial feedlot reveals farm-to-farm transmission of E. coli O157, likely via super-shedders. Our results reveal high risk factors in the prevalence of E. coli O157 in cattle whereby animal genetic and physiological factors influence whether this pathogen can persist in cattle at high concentration, providing insights to intervene this pathogen at the pre-harvest level. 相似文献