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21.
Background
HIV infection affects the populations of T helper cells, dendritic cells and macrophages. Moreover, it has a serious impact on the central nervous system. It is yet not clear whether this list is complete and why specifically those cell types are affected. To address this question, we have developed a method to identify cellular surface proteins that permit, mediate or enhance HIV infection in different cell/tissue types in HIV-infected individuals. Receptors associated with HIV infection share common functions and domains and are involved in similar cellular processes. These properties are exploited by bioinformatics techniques to predict novel cell surface proteins that potentially interact with HIV.Methodology/Principal Findings
We compiled a set of surface membrane proteins (SMP) that are known to interact with HIV. This set is extended by proteins that have direct interaction and share functional similarity. This resulted in a comprehensive network around the initial SMP set. Using network centrality analysis we predict novel surface membrane factors from the annotated network. We identify 21 surface membrane factors, among which three have confirmed functions in HIV infection, seven have been identified by at least two other studies, and eleven are novel predictions and thus excellent targets for experimental investigation.Conclusions
Determining to what extent HIV can interact with human SMPs is an important step towards understanding patient specific disease progression. Using various bioinformatics techniques, we generate a set of surface membrane factors that constitutes a well-founded starting point for experimental testing of cell/tissue susceptibility of different HIV strains as well as for cohort studies evaluating patient specific disease progression. 相似文献22.
Selective Lesions by Manganese and Extensive Damage by Iron After Injection into Rat Striatum or Hippocampus 总被引:3,自引:1,他引:2
W. N. Sloot A. J. van der Sluijs-Gelling J. B. P. Grambbergen† 《Journal of neurochemistry》1994,62(1):205-216
Abstract: Regional 45Ca2+ accumulation and analysis of monoamines and metabolites in dissected tissues were used to localize, quantify, and characterize brain damage after intracerebral injections of Mn2+ into striatum and hippocampus. The specificity of Mn2+-induced lesions is described in relation to brain damage produced by local Fe2+or 6-hydroxydopamine (6-OHDA) injections. In striatum, Fe2+ and Mn2+ produced dose-dependent (0.05-0.8 μmol) dopamine (DA) depletion, with Fe2+ being 3.4 times more potent than Mn2+. Studies examining the time course of changes in monoamine levels in striatum following local application of 0.4 μmol of Mn2+ revealed maximal depletion of all substances investigated (except 5-hydroxyin-doleacetic acid) after 3 days. The effects on DA (87% depletion at day 3) and its major metabolites were most pronounced and lasted until at least 90 days (40% depletion), whereas serotonin and noradrenaline levels recovered within 21 and 42 days, respectively. In addition, levels of 3-methoxytyramine, which is used as an index of DA release, also recovered within 42 days, indicating a functional restoration of DA neurotransmission despite substantial loss of DA content. Intrastriatal Mn2+ (0.4 μmol) produced time-dependent 45Ca2+ accumulation in striatum, globus pallidus, entopeduncular nucleus, several thalamic nuclei, and substantia nigra pars reticulata ipsilateral to the injection site. In contrast, 6-OHDA injected at a dose equipotent in depleting DA produced significantly less 45Ca2+ accumulation in striatum and globus pallidus and no labeling of other brain areas, whereas Fe2+ (0.4 μmol) produced extensive 45Ca2+ accumulation throughout basal ganglia, accumbens, and cerebral cortex. In hippocampus, high Mn2+ (0.4 μmol) produced limited 45Ca2+ accumulation in subiculum and dentate gyrus, whereas low Fe2+ (0.1 μmol) produced widespread 45Ca2+ accumulation throughout hippocampus, thalamus, and cerebral cortex. It is concluded that (a) Mn2+ is selectively neurotoxic to pathways intrinsic to the basal ganglia, (b) intrastriatal injections can be used as a model for systemic Mn2+ intoxications, and (c) high endogenous Fe3+ and/or catecholamine levels potentiate the neurotoxicity of Mn2+. 相似文献
23.
In many marine sessile organisms (for example sponges and stony corals) the skeleton is formed by an accretive growth process, where layers of material are secreted on top of each other in a surface normal deposition process. In many of these organisms the growth process exhibits a strong morphological plasticity due to differences in exposure to water movement. In general, many of these organisms tend to form thin-branching growth forms under sheltered conditions, while the growth form gradually transforms into a more compact shape when the exposure of water movement increases. In this paper, we investigate this phenomenon by combining a three-dimensional simulation model of radiate accretive growth driven by the local availability of simulated food particles and a model, based on the lattice Boltzmann method, for simulating food particle distributions caused by a combination of flow and diffusion. In the simulations two different models of a suspension feeder with accretive growth were compared. In the first model, the deposition process is exclusively driven by the local availability of food particles, in the second model the deposition process was determined by the combination of local amount of contact to the environment and availability of food particles. In the simulations it was found that hydrodynamics has a strong impact on the overall morphologies which develop in the accretive growth process. In the model exclusively driven by the local availability of food particles, column-shaped objects emerged under diffusion conditions, while more spherical and lobed object were found for the flow-dominated case. In the simulations, the Péclet number was varied independently from the Reynolds number, which was kept at a relatively low constant value. In a range of increasing Péclet numbers, indicating an increasing influence of hydrodynamics, the simulated morphologies gradually transformed from thin-branching ones into more spherical and compact morphologies in the model where deposition was controlled by the local availability of food particles and the local amount of contact with the environment. 相似文献
24.
Attempts to eliminate Sarcoptes scabiei var. suis were made in 2 naturally infested sow herds, by intramuscular (IM) injection of doramectin (Dectomax®, Pfizer, New York, USA). A single injection strategy was used. In one of the herds, the environment was treated with an acaricide following dry cleaning of floors, walls and equipment. In the second herd, no environmental treatment was performed. Results were measured by skin lesion scoring, ear scrapings to show Sarcoptes scabiei var. suis, and calculating rubbing index throughout the observation period of 20 months following treatment. Skin lesion scores decreased and stayed low following treatment for the entire observation period. Live Sarcoptes scabiei var. suis mites were isolated prior to treatment from both herds, but not following treatment. Rubbing index decreased following treatment, but was occasionally at or above 0.4. The results of these studies indicate that elimination of Sarcoptes scabiei var. suis from 2 naturally infested herds was successful, using doramectin in a single injection strategy. Precautions must be taken to ensure adequate dosing of every pig, and to avoid reinfestation due to poor biosecurity. 相似文献
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26.
Using a shore-based station we monitored the position of sperm whales (Physeter macrocephalus) within the Kaikoura submarine canyon from 2010 to 2012. We tracked sperm whales using a theodolite station for a total of 290 days. We extracted the distance from the nearest coast, the depth and the bathymetric slope using ArcGIS 10.1. We estimated the seasonal spatial distribution of sperm whales using general additive models. The distribution varied significantly between seasons; individuals were found in deeper water and further offshore in the spring than in winter. This study improved our understanding of the variability of sperm whale distribution patterns off Kaikoura. We determined that the distribution was linked to the bathymetric features and we hypothesized that whales adapted their use of the submarine canyon in relation to food aggregation. We would encourage further studies to evaluate the sperm whale relationship with oceanographic variables off Kaikoura. 相似文献
27.
Brooke E. Nichols Charles A. B. Boucher Janneke H. van Dijk Phil E. Thuma Jan L. Nouwen Rob Baltussen Janneke van de Wijgert Peter M. A. Sloot David A. M. C. van de Vijver 《PloS one》2013,8(3)
Background
Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine effectively prevents new HIV infections. The optimal scenario for implementing PrEP where most infections are averted at the lowest cost is unknown. We determined the impact of different PrEP strategies on averting new infections, prevalence, drug resistance and cost-effectiveness in Macha, a rural setting in Zambia.Methods
A deterministic mathematical model of HIV transmission was constructed using data from the Macha epidemic (antenatal prevalence 7.7%). Antiretroviral therapy is started at CD4<350 cells/mm3. We compared the number of infections averted, cost-effectiveness, and potential emergence of drug resistance of two ends of the prioritization spectrum: prioritizing PrEP to half of the most sexually active individuals (5–15% of the total population), versus randomly putting 40–60% of the total population on PrEP.Results
Prioritizing PrEP to individuals with the highest sexual activity resulted in more infections averted than a non-prioritized strategy over ten years (31% and 23% reduction in new infections respectively), and also a lower HIV prevalence after ten years (5.7%, 6.4% respectively). The strategy was very cost-effective at $323 per quality adjusted life year gained and appeared to be both less costly and more effective than the non-prioritized strategy. The prevalence of drug resistance due to PrEP was as high as 11.6% when all assumed breakthrough infections resulted in resistance, and as low as 1.3% when 10% of breakthrough infections resulted in resistance in both our prioritized and non-prioritized scenarios.Conclusions
Even in settings with low test rates and treatment retention, the use of PrEP can still be a useful strategy in averting infections. Our model has shown that PrEP is a cost-effective strategy for reducing HIV incidence, even when adherence is suboptimal and prioritization is imperfect. 相似文献28.
Verschueren E Vanhee P van der Sloot AM Serrano L Rousseau F Schymkowitz J 《Current opinion in structural biology》2011,21(4):452-459
Structure-based computational methods are popular tools for designing proteins and interactions between proteins because they provide the necessary insight and details required for rational engineering. Here, we first argue that large-scale databases of fragments contain a discrete but complete set of building blocks that can be used to design structures. We show that these structural alphabets can be saturated to provide conformational ensembles that sample the native structure space around energetic minima. Second, we show that catalogs of interaction patterns hold the key to overcome the lack of scaffolds when computationally designing protein interactions. Finally, we illustrate the power of database-driven computational protein design methods by recent successful applications and discuss what challenges remain to push this field forward. 相似文献
29.
Thomas Fleischer Arnoldo Frigessi Kevin C Johnson Hege Edvardsen Nizar Touleimat Jovana Klajic Margit LH Riis Vilde D Haakensen Fredrik W?rnberg Bj?rn Naume ?slaug Helland Anne-Lise B?rresen-Dale J?rg Tost Brock C Christensen Vessela N Kristensen 《Genome biology》2014,15(8)
Background
Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development.Results
We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma.Conclusions
This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0435-x) contains supplementary material, which is available to authorized users. 相似文献30.
Prosperi MC Rosen-Zvi M Altmann A Zazzi M Di Giambenedetto S Kaiser R Schülter E Struck D Sloot P van de Vijver DA Vandamme AM Sönnerborg A;EuResist study group;Virolab study group 《PloS one》2010,5(10):e13753