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291.
Adriana Turqueti-Neves Manuel Otte Christian Schwartz Michaela Erika Renate Schmitt Cornelia Lindner Oliver Pabst Philipp Yu David Voehringer 《PLoS biology》2015,13(11)
IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders. 相似文献
292.
Olivia Lenoir Magali Jasiek Carole Hénique Léa Guyonnet Bj?rn Hartleben Tillmann Bork Anna Chipont Kathleen Flosseau Imane Bensaada Alain Schmitt Jean-Marc Massé Michèle Souyri Tobias B Huber Pierre-Louis Tharaux 《Autophagy》2015,11(7):1130-1145
The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN. 相似文献
293.
294.
Motivation
In mass spectrometry-based proteomics, XML formats such as mzML and mzXML provide an open and standardized way to store and exchange the raw data (spectra and chromatograms) of mass spectrometric experiments. These file formats are being used by a multitude of open-source and cross-platform tools which allow the proteomics community to access algorithms in a vendor-independent fashion and perform transparent and reproducible data analysis. Recent improvements in mass spectrometry instrumentation have increased the data size produced in a single LC-MS/MS measurement and put substantial strain on open-source tools, particularly those that are not equipped to deal with XML data files that reach dozens of gigabytes in size.Results
Here we present a fast and versatile parsing library for mass spectrometric XML formats available in C++ and Python, based on the mature OpenMS software framework. Our library implements an API for obtaining spectra and chromatograms under memory constraints using random access or sequential access functions, allowing users to process datasets that are much larger than system memory. For fast access to the raw data structures, small XML files can also be completely loaded into memory. In addition, we have improved the parsing speed of the core mzML module by over 4-fold (compared to OpenMS 1.11), making our library suitable for a wide variety of algorithms that need fast access to dozens of gigabytes of raw mass spectrometric data.Availability
Our C++ and Python implementations are available for the Linux, Mac, and Windows operating systems. All proposed modifications to the OpenMS code have been merged into the OpenMS mainline codebase and are available to the community at https://github.com/OpenMS/OpenMS. 相似文献295.
296.
Christopher T. Lam Marlee S. Krieger Jennifer E. Gallagher Betsy Asma Lisa C. Muasher John W. Schmitt Nimmi Ramanujam 《PloS one》2015,10(9)
Introduction
Current guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA) of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope) for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies.Results
Our POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems.Conclusion
The POCkeT Colposcope is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system could potentially increase access to cervical cancer screening in limited resource settings through task shifting to community health workers. 相似文献297.
The emotional state can influence decision-making under ambiguity. Cognitive bias tests (CBT) proved to be a promising indicator of the affective valence of animals in a context of farm animal welfare. Although it is well-known that humans can influence the intensity of fear and reactions of animals, research on cognitive bias often focusses on housing and management conditions and neglects the role of humans on emotional states of animals. The present study aimed at investigating whether humans can modulate the emotional state of weaned piglets. Fifty-four piglets received a chronic experience with humans: gentle (GEN), rough (ROU) or minimal contact (MIN). Simultaneously, they were individually trained on a go/no-go task to discriminate a positive auditory cue, associated with food reward in a trough, from a negative one, associated with punishments (e.g. water spray). Independently of the treatment (P = 0.82), 59% of piglets completed the training. Successfully trained piglets were then subjected to CBT, including ambiguous cues in presence or absence of a human observer. As hypothesized, GEN piglets showed a positive judgement bias, as shown by their higher percentage of go responses following an ambiguous cue compared to ROU (P = 0.03) and MIN (P = 0.02) piglets, whereas ROU and MIN piglets did not differ (P > 0.10). The presence of an observer during CBT did not modulate the percentage of go responses following an ambiguous cue (P > 0.10). However, regardless of the treatment, piglets spent less time in contact with the trough following positive cues during CBT in which the observer was present than absent (P < 0.0001). This study originally demonstrates that the nature of a chronic experience with humans can induce a judgement bias indicating that the emotional state of farm animals such as piglets can be affected by the way humans interact with them. 相似文献
298.
Luning Wang Mikko J. Nissi Ferenc Tóth Jonah Shaver Casey P. Johnson Jinjin Zhang Michael Garwood Cathy S. Carlson Jutta M. Ellermann 《PloS one》2015,10(10)
Purpose
To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC) in goats.Methods
Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections.Results
All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG) loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues.Conclusions
Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions. 相似文献299.
300.
Mylarappa Ningappa Juhoon So Joseph Glessner Chethan Ashokkumar Sarangarajan Ranganathan Jun Min Brandon W. Higgs Qing Sun Kimberly Haberman Lori Schmitt Silvia Vilarinho Pramod K. Mistry Gerard Vockley Anil Dhawan George K. Gittes Hakon Hakonarson Ronald Jaffe Shankar Subramaniam Donghun Shin Rakesh Sindhi 《PloS one》2015,10(9)