Staging of biliary atresia at diagnosis by molecular profiling of the liver

Abstract Background Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. Methods We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Results Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. Conclusions Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/112492/1/13073_2010_Article_154.pd

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Not AvailableDevelopment of kunitz trypsin inhibitor (KTI)-free soybean is crucial for soy-food industry as the heat inactivation employed to inactivate the anti-nutritional factor in regular soybean incurs extra cost and affects protein solubility. In the presented work, a null allele of KTI from PI542044 was introgressed into cultivar ‘JS97-52’ (recurrent parent) through marker assisted backcrossing. Foreground selection in BC1F2, BC2F2 and BC3F2 was carried out using the null allele-specifc marker in tandem with SSR marker Satt228, tightly linked with a trypsin inhibitor Ti locus. Background selection in null allele-carrying plants through 106 polymorphic SSR markers across the genome led to the identifcation of 9 KTI-free lines exhibiting 98.6% average recurrent parent genome content (RPGC) after three backcrosses, which otherwise had required 5–6 backcrosses through conventional method. Introgressed lines (ILs) were free from KTI and yielded at par with recurrent parent. Reduction of 68.8–83.5% in trypsin inhibitor content (TIC) in ILs compared to the recurrent parent (‘JS97-52’) was attributed to the elimination of KTI.DB

Gene expression signature for biliary atresia and a role for interleukin‐8 in pathogenesis of experimental disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107580/1/hep27045.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107580/2/hep27045-sup-0001-suppinfo01.pd

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Not AvailableHigh-isoflavones soybean genotypes are desired in nutraceutical industry. Conversely, low-isoflavones soybean genotypes are preferred to regular soybean in designing soy-based infant formula and in developing soy food products with reduced astringent taste. Concentration of individual form of isoflavones viz. daidzein, glycitein and genistein was determined in the seeds of 46 Indian and exotic soybean genotypes using high performance liquid chromatography. The study exhibited a 9-fold (234.3-2092.5 µg/g of seed) genetic variation for total isoflavones content, with 19 genotypes falling in high isoflavones (>1200 µg/g), and 14 genotypes in low isoflavoes category (<600 µg/g). For developing genotypes with further high or low values of isoflavones, it is critical to hybridize genetically diverse parents with-in high or low-isoflavones genotypes as analysed by HPLC. Genetic diversity analysis carried out using 58 simple sequence (SSR) markers exhibited 144 alleles with polymorphic information content (PIC) varying from 0.00 to 0.773. The pair-wise genetic similarity value between soybean genotypes varied from 0.24 to 0.95. Unweighted Pair Group Method with Arithmetic Mean (UPGMA) allocated the genotypes in 5 clusters with fairly good bootstrap support. Mantel’s test for cophenetic correlation with r = 0.810 indicated a good fit of the soybean genotypes in a group in the cluster analysis. Genetically diverse parents identified in low- and high-isoflavones category can be crossed to obtain trangressive segregants.Not Availabl

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Not AvailableSoybean is regarded as “miracle bean” due to its numerous uses as food, feed and health supplement. However, acceptance of soy foods has been restricted by the presence of kunitz trypsin inhibitor (KTI) in soybean seeds. Kunitz trypsin inhibitor also known as SBTI-A2 which constitutes 80% of the total trypsin inhibitor activity, has been shown to be responsible for growth inhibition, pancreatic hypertrophy and hyperplasia in experimental animals [1-3]. Though KTI is heat labile, however, heat treatment is not only cost ineffective but also results in approximately 20% decline in protein solubility [4]. Similarly, boiling of beans prior to grinding with wheat (1:9) is essential while preparing soy-supplemented chapatti flour. Therefore, development of KTI-free soybean varieties which are not yet available in India is expected to boost utilization of soybean in food productsNot Availabl

Cxcr2 signaling and the microbiome suppress inflammation, bile duct injury, and the phenotype of experimental biliary atresia

<div><p>Biliary atresia is progressive fibro-inflammatory cholangiopathy of young children. Central to pathogenic mechanisms of injury is the tissue targeting by the innate and adaptive immune cells. Among these cells, neutrophils and the IL-8/Cxcl-8 signaling via its Cxcr2 receptor have been linked to bile duct injury. Here, we aimed to investigate whether the intestinal microbiome modulates Cxcr2-dependent bile duct injury and obstruction. Adult wild-type (WT) and <i>Cxcr2</i>^<i>-/-</i> mice were fed a diet supplemented with sulfamethoxazole/trimethoprim (SMZ/TMP) during pregnancy and lactation, and their pups were injected intraperitoneally with rhesus rotavirus (RRV) within 24 hours of life to induce experimental biliary atresia. The maternal exposure to SMZ/TMP significantly lowered the incidence of jaundice and bile duct obstruction and resulted in improved survival, especially in <i>Cxcr2</i>^<i>-/-</i> mice. Analyses of the microbiome by deep sequencing of 16S rRNA of the neonatal colon showed a delay in bacterial colonization of WT mice induced by SMZ/TMP, with a notable switch from <i>Proteobacteria</i> to <i>Firmicutes</i>. Interestingly, the genetic inactivation of <i>Cxcr2</i> alone produced a similar bacterial shift. When treated with SMZ/TMP, <i>Cxcr2</i>^<i>-/-</i> mice infected with RRV to induce experimental biliary atresia showed further enrichment of <i>Corynebacterium</i>, <i>Anaerococcus</i> and <i>Streptococcus</i>. Among these, <i>Anaerococcus lactolyticus</i> was significantly associated with a suppression of biliary injury, cholestasis, and survivability. These results suggest that the postnatal development of the intestinal microbiota is an important susceptibility factor for experimental biliary atresia.</p></div

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Not AvailableSoybean is regarded as “miracle bean” due to its numerous uses as food, feed and health supplement. However, acceptance of soy foods has been restricted by the presence of kunitz trypsin inhibitor (KTI) in soybean seeds. Kunitz trypsin inhibitor also known as SBTI-A2 which constitutes 80% of the total trypsin inhibitor activity, has been shown to be responsible for growth inhibition, pancreatic hypertrophy and hyperplasia in experimental animals [1-3]. Though KTI is heat labile, however, heat treatment is not only cost ineffective but also results in approximately 20% decline in protein solubility [4]. Similarly, boiling of beans prior to grinding with wheat (1:9) is essential while preparing soy-supplemented chapatti flour. Therefore, development of KTI-free soybean varieties which are not yet available in India is expected to boost utilization of soybean in food products.Not Availabl