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Hirschsprung disease (HSCR) is a common cause of intestinal obstruction in the newborn. Hirschsprung-associated enterocolitis (HAEC) is a significant and life-threatening complication of HSCR, affecting up to 60% of patients. Animal models of endothelin receptor B (EdnrB) mutation reliably model human HSCR and HAEC. We previously demonstrated intestinal dysbiosis and a gut-specific deficiency of B-lymphocyte–produced secretory IgA (sIgA), the primary effector molecule of mucosal immunity, in mice with homozygous neural crest cell–conditional deletion of EdnrB (EdnrB(NCC−/−)). To determine mechanisms for sIgA deficiency, we examined intrinsic and extrinsic aspects of B-lymphocyte development and function. Expression of the endothelin axis components [endothelin-1 (ET-1), endothelin-3 (ET-3), endothelin receptor A (EdnrA), EdnrB] were determined over a developmental time course. B-lymphocyte survival and Ig production were assayed in vitro. Polymeric Ig receptor (pIgR)–mediated IgA transport into the intestinal lumen was interrogated. We found endothelin axis component (EdnrA, EdnrB, ET-1, ET-3) expression in developing extramedullary hematopoietic organs and that some splenic B lymphocytes express EdnrB. Splenic B lymphocytes from EdnrB(NCC−/−) mice showed no intrinsic defect in survival vs. wild-type (WT) B lymphocytes. In vitro stimulation of splenic B lymphocytes demonstrated decreased IgA, IgG, and IgM production in EdnrB(NCC−/−) vs. WT mice. Additionally, small intestinal pIgR was decreased ∼50% in EdnrB(NCC−/−) mice. These results suggest an intrinsic B-lymphocyte defect in antibody production as well as an extrinsic defect in IgA transport in the EdnrB(NCC−/−) model of HAEC. Our results are consistent with human HAEC observations of decreased luminal sIgA and mouse models of other inflammatory bowel diseases, in which decreased pIgR is seen in concert with a dysregulated microbiota. Finally, our results suggest targeting the dysbiotic microbiome and pIgR-mediated sIgA transport as potential therapeutic approaches in prevention and treatment of HAEC.—Medrano, G., Cailleux, F., Guan, P., Kuruvilla, K., Barlow-Anacker, A. J., Gosain, A. B-lymphocyte–intrinsic and –extrinsic defects in secretory immunoglobulinA production in the neural crest–conditional deletion of endothelin receptor B model of Hirschsprung-associated enterocolitis.

The transverse asymmetry of the index modulation profile in the asymmetric few-mode fiber Bragg grating (FM-FBG) was investigated. The transverse asymmetry of the index modulation profile will lead to mode conversion between modes with the different azimuthal orders, and this asymmetry is characterized by the attenuation coefficient α. We evaluated that the value of attenuation coefficient α was 0.2 μm−1, and grating amplitude χ was 2.8 × 10−4 for FM-FBG inscribed by UV single-side illumination. We found that the optimized value of α was 0.16 μm−1, at which the maximum mode conversion efficiency of LP01–LP11 can be achieved. The results of this paper provide great potential application in few-mode fiber (FMF) devices and mode division multiplexing (MDM) optical communication.

A mode selective comb filter based on the Mach–Zehnder interferometer (MZI) is proposed and theoretically analyzed. The proposed filter consists of two vector mode selective couplers (MSCs). The vector MSCs are used to convert the fundamental mode to the second order vector modes. Both the wavelength selection and the mode selection functions with a broad bandwidth can be obtained in the proposed filter. Meanwhile, the proposed filter shows excellent comb filtering effects for both the fundamental mode and the second order mode in the C-band. Especially, the coupling efficiency of the second order mode is larger than 96% in the wavelength range from 1540 nm to 1560 nm. The proposed filter can find applications in the fields of the advanced optical fiber lasers, mode division multiplexing (MDM) systems and wavelength division multiplexing (WDM) systems.

Omega-3 long-chain polyunsaturated fatty acids (ω3PUFA) have been shown to be antiinflammatory in the attenuation of hepatocellular injury. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that inhibits the activation of nuclear factor κB, thereby repressing inflammation, and ωPUFA are PPARα ligands. The purpose of this study was to determine if ω3PUFA attenuate bile acid-induced apoptosis via PPARα.Human hepatocellular carcinoma (HepG2) cells were treated with chenodeoxycholic acid (CDCA) ± ω3PUFA. Activation of PPARα was evaluated, and expression of PPARα, farnesoid X receptor, liver X receptor alpha (LXRα), and retinoid X receptor mRNA was evaluated by reverse-transcriptase PCR.PPARα activation was increased in HepG2 cells treated with ω3PUFA, and decreased in the presence of CDCA when compared with untreated cells. PPARα mRNA was reduced by 67% with CDCA and restored to the level of control with ω3PUFA. LXRα mRNA increased twofold with CDCA treatment and was significantly reduced by ω3PUFA.Expression of PPARα, as well as LXRα mRNA levels, was reduced with CDCA treatment and restored with the addition of ω3PUFA. These results suggest that PPARα and LXRα may be mediators by which ω3PUFA attenuate bile acid-induced hepatocellular injury.

The purpose of this study was to perform a comprehensive evaluation and selection of reference genes for the study of extramedullary hematopoiesis during development and the early post-natal period. A total of six candidate reference genes (ACTB, GAPDH, HPRT1, PPID, TBP, TUBB3) in four organs (heart, liver, spleen, and thymus) over five perinatal time points (Embryonic days 14.5, 16.5, 18.5, Post-natal days 0, 21) were evaluated by quantitative real-time PCR. The expression stability of the candidate reference genes were analyzed using geNorm, NormFinder, Bestkeeper, Delta CT method, and RefFinder software packages. Detailed methodology for isolation of high quality/purity RNA and analysis is presented. Detailed analysis demonstrated that TBP is the best single reference gene for embryonic samples and HPRT1 is the best single reference gene for post-natal and pooled embryonic and post-natal samples. Organ-level analysis demonstrated that HPRT1 was the most suitable reference gene for heart, liver and thymus samples, while TBP was the best candidate for spleen samples. In general, TUBB3 was consistently the least stable gene for normalization. This is the first study to describe a systematic comprehensive selection of reference genes for murine extramedullary hematopoietic tissues over a developmental time course. We provide suggested reference genes for individual tissues and developmental stages and propose that a combination of reference genes affords flexibility in experimental design and analysis.