Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

peer reviewe

Structure and Complexity of a Bacterial Transcriptome▿ †

Although gene expression has been studied in bacteria for decades, many aspects of the bacterial transcriptome remain poorly understood. Transcript structure, operon linkages, and information on absolute abundance all provide valuable insights into gene function and regulation, but none has ever been determined on a genome-wide scale for any bacterium. Indeed, these aspects of the prokaryotic transcriptome have been explored on a large scale in only a few instances, and consequently little is known about the absolute composition of the mRNA population within a bacterial cell. Here we report the use of a high-throughput sequencing-based approach in assembling the first comprehensive, single-nucleotide resolution view of a bacterial transcriptome. We sampled the Bacillus anthracis transcriptome under a variety of growth conditions and showed that the data provide an accurate and high-resolution map of transcript start sites and operon structure throughout the genome. Further, the sequence data identified previously nonannotated regions with significant transcriptional activity and enhanced the accuracy of existing genome annotations. Finally, our data provide estimates of absolute transcript abundance and suggest that there is significant transcriptional heterogeneity within a clonal, synchronized bacterial population. Overall, our results offer an unprecedented view of gene expression and regulation in a bacterial cell

Total Phenolic Compounds Extraction in Leaves of Ocimum gratissimum L. and Their Potential Activity against Some Agricultural Contaminants

Aims: Phenolic compounds are secondary metabolites that are important in the plant due to their role in plant defense and their antioxidant activity with other biological properties such as antipyretic, analgesic and antimicrobial activities. This study focused on the biological potential activity of total phenolic compounds extracted by soxhlet method from Ocimum gratissimum leaves (Lamiaceae), a popular medicinal plant harvested at Daloa (Côte d’Ivoire). Study Design: Activities were directed on the in vitro antifungal and antioxidant activities combined to phenolic compounds analysis. Place and Duration of Study: The study was carried out at the Department of Environment and Plant Protection, and Laboratory of Chemistry and Biochemistry, University of Agricultural Sciences and Veterinary Medicine (USAMV) between March to July 2014, Laboratory of Biochemistry and Microbiology (Bioactives Natural Substances Unit), Jean Lorougnon Guédé University between September 2014 to January 2015. Methodology: The extract obtained named TPCOG was tested against Fusarium species for its antifungal activity by applying agar slant double dilution method and for its antioxidant activity by DPPH radical scavenging assay. Qualitative and quantitative evaluation of phenolic compounds were carried out by HPLC analysis method with sigma chemical standards. Results: Tests showed that TPCOG was a powerful antifungal extract with MIC and MFC ranging between 3.125 µg/mL to 12.5 µg/mL. This extract was fungicidal and its antioxidant activity reached F= 541.25± .25 mM Trolox/mL (I= 70 ±1.85%) with a total phenolic content equal 195.70±1.33 mg GAE/g. Radical scavenge and antifungal activities correlated very well with total phenolic compounds. Phenolic content analysis showed presence of phenolic acids and flavonoids with a higher concentration for Quercetin (393.475 mg/100 g sample). Conclusion: All this results demonstrated the biological potential activity of total phenolic compounds extracted from leaves of O. gratissimum and the possibility to use it in replace to essential oil for the formulation of biofungicides and nutraceuticals by industries