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151.
152.
James Kaufman Justin Lessler April Harry Stefan Edlund Kun Hu Judith Douglas Christian Thoens Bernd Appel Annemarie K?sbohrer Matthias Filter 《PLoS computational biology》2014,10(7)
Foodborne disease outbreaks of recent years demonstrate that due to increasingly interconnected supply chains these type of crisis situations have the potential to affect thousands of people, leading to significant healthcare costs, loss of revenue for food companies, and—in the worst cases—death. When a disease outbreak is detected, identifying the contaminated food quickly is vital to minimize suffering and limit economic losses. Here we present a likelihood-based approach that has the potential to accelerate the time needed to identify possibly contaminated food products, which is based on exploitation of food products sales data and the distribution of foodborne illness case reports. Using a real world food sales data set and artificially generated outbreak scenarios, we show that this method performs very well for contamination scenarios originating from a single “guilty” food product. As it is neither always possible nor necessary to identify the single offending product, the method has been extended such that it can be used as a binary classifier. With this extension it is possible to generate a set of potentially “guilty” products that contains the real outbreak source with very high accuracy. Furthermore we explore the patterns of food distributions that lead to “hard-to-identify” foods, the possibility of identifying these food groups a priori, and the extent to which the likelihood-based method can be used to quantify uncertainty. We find that high spatial correlation of sales data between products may be a useful indicator for “hard-to-identify” products. 相似文献
153.
154.
Roman Volchenkov Johan G Brun Roland Jonsson Silke Appel 《Arthritis research & therapy》2013,15(5):R114
Introduction
Therapeutic vaccination with antigen-specific tolerogenic dendritic cells (tolDC) might become a future option of individualized therapy for patients with autoimmune diseases. In this study, we tested the possibility of generating monocyte-derived tolDC from patients with primary Sjögren''s syndrome (pSS). We analyzed phenotype, cytokine production and ability to suppress Ro/La-specific immune responses.Methods
Monocyte-derived tolDC from patients with pSS were generated in the presence of dexamethasone, vitamin D3 and lipopolysaccharide (DexVD3 DC). The phenotype was analyzed by flow cytometry and the cytokine profile was investigated using a 25-plex Luminex assay and ELISA. The capacity to both stimulate Ro/La-specific T cells and suppress this response was evaluated by autologous mixed lymphocyte reaction (MLR).Results
DC generated from patients with pSS had a similar phenotype and cytokine profile to those from healthy controls. DexVD3 DC from pSS patients induced little antigen-specific T cell proliferation, but DexVD3 DC-primed lymphocytes successfully suppressed Ro/La-specific T cell responses.Conclusions
DexVD3 DC presenting Ro/La antigens might be a promising new therapeutic option for patients with pSS. 相似文献155.
Hafez Hala A. Kamel Maher A. Osman Mohamed Y. Osman Hassan MY. Elblehi Samar S. Mahmoud Shimaa A. 《Molecular and cellular biochemistry》2021,476(5):2233-2249
Molecular and Cellular Biochemistry - Alzheimer’s disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental... 相似文献
156.
Appel H Maier R Wu P Scheer R Hempfing A Kayser R Thiel A Radbruch A Loddenkemper C Sieper J 《Arthritis research & therapy》2011,13(3):R95
Introduction
In this study, we analysed the number of IL-17+ cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls. 相似文献157.
Yongye Austin B. Pinilla Clemencia Medina-Franco Jose L. Giulianotti Marc A. Dooley Colette T. Appel Jon R. Nefzi Adel Scior Thomas Houghten Richard A. Martínez-Mayorga Karina 《Journal of molecular modeling》2011,17(6):1473-1482
Mixture-based synthetic combinatorial library (MB-SCL) screening is a well-established experimental approach for rapidly retrieving
structure–activity relationships (SAR) and identifying hits. Virtual screening is also a powerful approach that is increasingly
being used in drug discovery programs and has a growing number of successful applications. However, limited efforts have been
made to integrate both techniques. To this end, we combined experimental data from a MB-SCL of bicyclic guanidines screened
against the κ-opioid receptor and molecular similarity methods. The activity data and similarity analyses were integrated
in a biometric analysis–similarity map. Such a map allows the molecules to be categorized as actives, activity cliffs, low
similarity to the reference compounds, or missed hits. A compound with IC50 = 309 nM was found in the “missed hits” region, showing that active compounds can be retrieved from a MS-SCL via computational
approaches. The strategy presented in this work is general and is envisioned as a general-purpose approach that can be applied
to other MB-SCLs. 相似文献
158.
Judkowski V Bunying A Ge F Appel JR Law K Sharma A Raja-Gabaglia C Norori P Santos RG Giulianotti MA Slifka MK Douek DC Graham BS Pinilla C 《PloS one》2011,6(9):e24091
The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens. 相似文献
159.
Insect repellents are widely used to protect against insect bites and thus prevent allergic reaction and the spread of disease. To gain insight into the mosquito’s response to chemicals repellents, we investigated the interaction between the olfactory system of the mosquito Culex quinquefasciatus Say and chemical repellents using single sensillum recording. The interactions of 50 repellent chemicals with olfactory receptor neurons were measured in six different types of mosquito sensilla: long sharp trichoid (LST), short sharp trichoid (SST), short blunt trichoid I (SBT-I), short blunt trichoid II (SBT-II), short blunt trichoid-curved (SBT-C), and grooved peg (GP). A single olfactory neuron reacted to the chemical repellents in each of the sensilla except for SBT-I and SBT-II, where two neurons were involved. Other than LST and GP, which showed no or very weak responses to the repellents tested, all the sensilla showed significant excitatory responses to certain types of repellents. Terpene-derived chemicals such as eucalyptol, α-pinene, and camphor, stimulated olfactory receptor neurons in a dose-dependent manner and mosquitoes responded more strongly to terpene-derived chemical repellents than to non-terpene-derived chemicals such as dimethyl phthalate. Mosquitoes also exhibited a similar response to stereoisomers of chemicals such as (−)-β-pinene versus (+)-β-pinene, and (−)-menthone versus (+)-menthone. This study not only demonstrates the effects of chemical repellents on the mosquito olfactory system but also provides important information that will assist those screening new mosquito repellents and designing new mosquito control agents. 相似文献
160.
Jade de Oliveira Eduardo Luiz Gasnhar Moreira Gianni Mancini Mariana Appel Hort Alexandra Latini Rosa Maria Ribeiro-do-Valle Marcelo Farina João Batista Teixeira da Rocha Andreza Fabro de Bem 《Neurochemical research》2013,38(10):2028-2036
Recent studies have indicated a causal link between high dietary cholesterol intake and brain oxidative stress. In particular, we have previously shown a positive correlation between elevated plasma cholesterol levels, cortico-cerebral oxidative stress and mitochondrial dysfunction in low density lipoprotein receptor knockout (LDLr?/?) mice, a mouse model of familial hypercholesterolemia. Here we show that the organoselenium compound diphenyl diselenide (PhSe)2 (1 mg/kg; o.g., once a day for 30 days) significantly blunted the cortico-cerebral oxidative stress and mitochondrial dysfunction induced by a hypercholesterolemic diet in LDLr?/? mice. (PhSe)2 effectively prevented the inhibition of complex I and II activities, significantly increased the reduced glutathione (GSH) content and reduced lipoperoxidation in the cerebral cortex of hypercholesterolemic LDLr?/? mice. Overall, (PhSe)2 may be a promising molecule to protect against hypercholesterolemia-induced effects on the central nervous system, in addition to its already demonstrated antiatherogenic effects. 相似文献