Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study

Abstract Background We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. Methods Twenty-nine patients (15 with Crohn’s disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate–labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. Results In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn’s disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). Conclusions Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF–responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders

Head-on collision of ion acoustic solitary waves in electron-positron-ion plasma with superthermal electrons and positrons

The head-on collision of ion acoustic solitary waves are studied in an electron-positron-ion plasma composed of superthermal electrons, superthermal positrons, and cold ions using the extended Poincaré-Lighthill-Kuo (PLK) method. The effects of the ratio of electron to positron temperature, the spectral index of electron and positron, and the concentration of positron component on the phase shift are studied. It is found that the presence of superthermal electrons and superthermal positrons play a significant role on the collision of ion acoustic solitary waves. It is also been observed that the temperature ratio plays a significant role on the collision of ion acoustic solitary waves

Head-on collision of ion acoustic solitary waves in an electron-positron-ion plasma with superthermal electrons

The head-on collision of ion acoustic solitary waves in a three-component unmagnetized plasma with cold ions, Boltzmann distributed positrons, and superthermal electrons is investigated using the extended Poincare-Lighthill-Kuo method. The effects of the ratio of electron temperature to positron temperature, the spectral index, kappa, of the electron kappa distribution, and fractional concentration of positron component (p) on the phase shift are studied. It is found that the presence of superthermal electrons play a significant role on the collision of ion acoustic solitary waves. (C) 2010 American Institute of Physics.[doi:10.1063/1.3528544

Head-on collision of ion acoustic solitary waves in an electron-positron-ion plasma with superthermal electrons

The head-on collision of ion acoustic solitary waves in a three-component unmagnetized plasma with cold ions, Boltzmann distributed positrons, and superthermal electrons is investigated using the extended Poincare-Lighthill-Kuo method. The effects of the ratio of electron temperature to positron temperature, the spectral index, kappa, of the electron kappa distribution, and fractional concentration of positron component (p) on the phase shift are studied. It is found that the presence of superthermal electrons play a significant role on the collision of ion acoustic solitary waves. (C) 2010 American Institute of Physics.[doi:10.1063/1.3528544

Molecular and morphological diversity in Rhizoctonia bataticola isolates causing dry root rot of chickpea (Cicer arietinum L.) in India

Dry root rot caused by Rhizoctonia bataticola (Taub.) Butler. [Pycnidial stage: Macrophomina phaseolina (Tassi) Goid] is emerging as a serious biotic constraint for chickpea production. To find out the diversity in R. bataticola populations in India, a total of 94 isolates collected from R. bataticola infected chickpea plants from different agro climatic regions of India were analyzed with amplified fragment length polymorphism (AFLP) and different morphological properties. R. bataticola populations collected from different agro-ecological zones were very diverse in respect to their different cultural and morphological parameters like colony color, growth pattern, growth rate, mycelial characters, sclerotial initiation time, sclerotial intensity and morphology of the sclerotia. Five AFLP primer combinations provided a total 121 fragments. All fragments were found polymorphic with an average polymorphic information content value of 0.213. The dendrogram based on AFLP analysis showed that the maximum number of R. bataticola isolates were very diverse and did not depend on geographical origin. Both morphological and molecular data correlated each other and supported that the R. bataticola present in India were diverse and independent to their origin

Molecular and morphological diversity in Rhizoctonia bataticola isolates causing dry root rot of chickpea (Cicer arietinum L.) in India

Dry root rot caused by Rhizoctonia bataticola (Taub.) Butler. [Pycnidial stage: Macrophomina phaseolina (Tassi) Goid] is emerging as a serious biotic constraint for chickpea production. To find out the diversity in R. bataticola populations in India, a total of 94 isolates collected from R. bataticola infected chickpea plants from different agro climatic regions of India were analyzed with amplified fragment length polymorphism (AFLP) and different morphological properties. R. bataticola populations collected from different agro-ecological zones were very diverse in respect to their different cultural and morphological parameters like colony color, growth pattern, growth rate, mycelial characters, sclerotial initiation time, sclerotial intensity and morphology of the sclerotia. Five AFLP primer combinations provided a total 121 fragments. All fragments were found polymorphic with an average polymorphic information content value of 0.213. The dendrogram based on AFLP analysis showed that the maximum number of R. bataticola isolates were very diverse and did not depend on geographical origin. Both morphological and molecular data correlated each other and supported that the R. bataticola present in India were diverse and independent to their origin

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Not AvailableProteomics has enormous applications in human and animal research. However, proteomic studies in fisheries science are quite scanty particularly for economically important species. Few proteomic studies have been carried out in model fish species, but comprehensive proteomics of aquaculture species are still scarce. This study aimed to perform a comprehensive organ-based protein profiling of important tissue samples for one of the most important aquaculture species,Labeo rohita.Deep proteomic profiling of 17 histologically normal tissues, blood plasma, and embryo provided mass-spectrometric evidence for 8498 proteins at 1% false discovery rate that make up about 26% of the total annotated protein-coding sequences in Rohu. Tissue-wise expression analysis was performed, and the presence of several biologically important proteins was also verified using a targeted proteomic approach. We identified the global post-translational modifications (PTMs) in terms of acetylation (N-terminus and lysine), methylation (N-terminus, lysine, and arginine), and phosphorylation (serine, threonine, and tyrosine) to present a comprehensive proteome resource. An interactive web-based portal has been developed for an overall landscape of protein expression across the studied tissues of Labeo rohita (www.fishprot.org). This draft proteome map of Labeo rohita would advance basic and applied research in aquaculture to meet the most critical challenge of providing food and nutritional security to an increasing world population.Not Availabl