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131.
Stephen L. Hicks Rakesh Sharma Amad N. Khan Claire M. Berna Andrea Waldecker Kevin Talbot Chris Kennard Martin R. Turner 《PloS one》2013,8(12)
The neurodegenerative disorder amyotrophic lateral sclerosis may render patients unable to speak or write, so that objective assessment of cognitive impairment, which is commonly of a dysexecutive nature, is challenging. There is therefore a need to develop other methods of assessment that utilize other relatively unaffected motor systems. In this proof-of-principle study a novel eye-tracking version of the trail-making test was compared with performance on the standard written version in a group of healthy volunteers. There was good correlation for speed between both versions of Part B (R2=0.73), suggesting that this is a viable method to objectively assess cognitive impairment in disorders where patients are unable to speak or write. 相似文献
132.
Introduction
To evaluate the effect of late initiation of HAART and poor immune reconstitution on the frequency of regulatory T-cells (Treg) in the peripheral blood and gut of HIV-infected patients, we studied Colombian HIV-infected patients who had been on suppressive HAART for at least one year. They had undetectable viremia but were either immunological responders (HIR); (CD4 counts >500 cells/µl) or non-immunological responders (NIR); (CD4 T-cell count <300 cells/µl). Untreated HIV-infected patients and uninfected controls from the same region were also evaluated.Methods
Frequency and phenotype of regulatory T-cells (Treg) were analyzed in gut biopsies and blood samples. The functional effect of Treg depletion on CMV and HIV responses was determined. Markers of immune activation and circulating LPS levels were quantified.Results
Untreated patients exhibited high Treg frequency in PBMC and gut, and their Treg express high levels of CTLA-4 and PD-1. Although HAART significantly decreased mucosal Treg frequency, it did not normalize it in any of the treated groups (HIR and NIR patients). Treg normalization was observed in the blood of HIR patients following HAART, but did not occur in NIR patients. Treg from HIV-infected patients (treated or not) suppressed HIV and hCMV-specific T-cells from gut and blood. Plasma LPS levels and percentage of HLA-DR+CD38+ T-cells were significantly elevated in all infected groups compared to controls.Conclusions
These findings suggest that control of viral replication is not sufficient to normalize gut Treg frequency in patients, independent of their response to HAART. Furthermore, persistence of functional Treg in the gut appears to be associated with the failure of HAART to repair mucosal damage. 相似文献133.
Yongqiang Li Claire A. Farnsworth Chris W. Coppin Mark G. Teese Jian-Wei Liu Colin Scott Xing Zhang Robyn J. Russell John G. Oakeshott 《PloS one》2013,8(10)
Two mutations have been found in five closely related insect esterases (from four higher Diptera and a hymenopteran) which each confer organophosphate (OP) hydrolase activity on the enzyme and OP resistance on the insect. One mutation converts a Glycine to an Aspartate, and the other converts a Tryptophan to a Leucine in the enzymes’ active site. One of the dipteran enzymes with the Leucine mutation also shows enhanced activity against pyrethroids. Introduction of the two mutations in vitro into eight esterases from six other widely separated insect groups has also been reported to increase substantially the OP hydrolase activity of most of them. These data suggest that the two mutations could contribute to OP, and possibly pyrethroid, resistance in a variety of insects. We therefore introduced them in vitro into eight Helicoverpa armigera esterases from a clade that has already been implicated in OP and pyrethroid resistance. We found that they do not generally enhance either OP or pyrethroid hydrolysis in these esterases but the Aspartate mutation did increase OP hydrolysis in one enzyme by about 14 fold and the Leucine mutation caused a 4–6 fold increase in activity (more in one case) of another three against some of the most insecticidal isomers of fenvalerate and cypermethrin. The Aspartate enzyme and one of the Leucine enzymes occur in regions of the H. armigera esterase isozyme profile that have been previously implicated in OP and pyrethroid resistance, respectively. 相似文献
134.
Jean-Emmanuel Bibault Sylvain Dewas Claire Vautravers-Dewas Antoine Hollebecque Hajer Jarraya Thomas Lacornerie Eric Lartigau Xavier Mirabel 《PloS one》2013,8(10)
Purpose
Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has been evaluated in several recent studies. The CyberKnife® is an SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the prognostic factors for local control and overall survival following this treatment.Patients and Methods
75 patients with 96 liver-confined HCC were treated with SBRT at the Oscar Lambret Comprehensive Cancer Center. Fiducials were implanted in the liver before treatment and were used as markers to track the lesion’s movement. Treatment response was scored according to RECIST v1.1. Local control and overall survival were calculated using the Kaplan and Meier method. A stepwise multivariate analysis (Cox regression) of prognostic factors was performed for local control and overall survival.Results
There were 67 patients with Child-Turcotte-Pugh (CTP) Class A and eight patients with CTP Class B. Treatment was administered in three sessions. A total dose of 40–45 Gy to the 80% isodose line was delivered. The median follow-up was 10 months (range, 3–49 months). The local control rate was 89.8% at 1 and 2 years. Overall survival was 78.5% and 50.4% at 1 and 2 years, respectively. Toxicity mainly consisted of grade 1 and grade 2 events. Higher alpha-fetoprotein (aFP) levels were associated with less favorable local control (HR=1.001; 95% CI [1.000, 1.002]; p=0.0063). A higher dose was associated with better local control (HR=0.866; 95% CI [0.753, 0.996]; p=0.0441). A Child-Pugh score higher than 5 was associated with worse overall survival (HR= 3.413; 95% CI [1.235, 9.435]; p=0.018).Conclusion
SBRT affords good local tumor control and higher overall survival rates than other historical controls (best supportive care or sorafenib). High aFP levels were associated with lesser local control, but a higher treatment dose improved local control. 相似文献135.
Mélanie Chabaud Noémie Paillon Katharina Gaus Claire Hivroz 《Biology of the cell / under the auspices of the European Cell Biology Organization》2020,112(7):196-212
To mount an immune response, T cells must first find rare antigens present at the surface of antigen-presenting cells (APCs). They achieve this by migrating rapidly through the crowded space of tissues and constantly sampling the surface of APCs. Upon antigen recognition, T cells decelerate and polarise towards the APC, ultimately forming a specialised interface known as the immunological synapse. These conjugates form as the result of the interaction between pairs of receptors/ligands that are under mechanical stress due to the continuously reorganising cell cytoskeleton. In this review, we discuss the involvement of mechanical forces during antigen recognition by migrating T cells. We will explore this question from a conceptual and technical perspective, with the aim of providing new insights into the emerging field of mechanobiology. 相似文献
136.
Potential for Virus Endogenization in Humans through Testicular Germ Cell Infection: the Case of HIV
137.
1. Since its recent arrival in Britain, the planthopper Prokelisia marginata has spread widely around saltmarshes on the east and south coast of England and south Wales, feeding on Common Cordgrass, Spartina anglica, itself an invasive non-native species. 2. Results suggest that P. marginata populations in Britain benefit from a degree of natural enemy release. No evidence of parasitism was found in over 71 000 eggs, nymphs, and adults inspected. The only potential natural enemy control was suggested by a positive correlation between the densities of planthoppers and generalist spiders. 3. Experimental exposure under both glasshouse and field conditions to typical field densities of planthoppers resulted in significant negative effects on a number of host plant performance metrics. 4. Spartina anglica is important for stabilising estuarine sediments and has been deliberately planted for this purpose in the past. Its weakening as a result of heavy planthopper herbivory could have serious consequences for the long-term stability of Britain's vulnerable saltmarsh habitats. 相似文献
138.
Fredrik Christiansen Mia L. K. Nielsen Claire Charlton Lars Bejder Peter T. Madsen 《Marine Mammal Science》2020,36(3):953-963
Unmanned aerial vehicles (UAVs) are increasingly used for wildlife research and monitoring, but little information exists on their potential effect on marine mammals. We assessed the effects of a UAV on the behavior of southern right whales (Eubalaena australis) in Australia. Focal follows of ten right whale mother-calf pairs were conducted using a theodolite. Control data were recorded for 30 min, and then a DJI Inspire 1 Pro was flown above the whales for 10 min at 5 m altitude. Potential changes to horizontal behavior (swim speed and turning angle) and surfacing pattern (interbreath intervals) were investigated by comparing mother-calf behavior before and during UAV approaches. Changes in respiration rate were used to quantify energetic effects. We also explored acoustic cue perceptibility of the UAV at 5, 10, and 30 m altitude, by measuring the received UAV underwater noise level on whales equipped with acoustic tags (DTAGs). The received noise levels were 86.0 ± 3.9 dB re 1 μPa, while the measured ambient noise was 80.7 ± 7.3 dB re 1 μPa in the same frequency band (100–1,500 Hz). No behavioral response to the UAV was observed. This provides support for UAVs as a noninvasive tool to study baleen whale behavior and ecophysiology. 相似文献
139.
Harlequin ichthyosis (HI) is a devastating autosomal recessive congenital skin disease. It has been vital to elucidate the biological importance of the protein ABCA12 in skin-barrier permeability, following the discovery that ABCA12 gene mutations can result in this rare disease. ATP-binding cassette transporter A12 (ABCA12) is a member of the subfamily of ATP-binding cassette transporters and functions to transport lipid glucosylceramides (GlcCer) to the extracellular space through lamellar granules (LGs). GlcCer are hydrolysed into hydroxyceramides extracellularly and constitute a portion of the extracellular lamellar membrane, lipid envelope and lamellar granules. In HI skin, loss of function of ABCA12 due to null mutations results in impaired lipid lamellar membrane formation in the cornified layer, leading to defective permeability of the skin barrier. In addition, abnormal lamellar granule formation (distorted shape, reduced in number or absent) could further cause aberrant production of LG-associated desquamation enzymes, which are likely to contribute to the impaired skin barrier in HI. This article reviews current opinions on the patho-mechanisms of ABCA12 action in HI and potential therapeutic interventions based on targeted molecular therapy and gene therapy strategies. 相似文献
140.