Genes in the Ureteric Budding Pathway: Association Study on Vesico-Ureteral Reflux Patients

Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureteric budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs) capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p<0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ∼50% showed a clear-cut primary VUR phenotype and ∼25% had both a duplex collecting system and VUR. We also looked for association in these two extreme phenotype groups. None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A) show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2) or duplex collecting system (EYA1 and UPK3A). SNPs in three genes (TGFB1, GNB3 and VEGFA) have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study. This is the first extensive study of common variants in the genes of the ureteric budding pathway and the genetic susceptibility to primary VUR

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

Serological Evidence of Avian Influenza in Captive Wild Birds in a Zoo and Two Safari Parks in Bangladesh

Avian influenza (AI) is endemic and frequently causes seasonal outbreaks in winter in Bangladesh due to high pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H9N2. Among avian influenza A viruses (AIV), H5, H7, and H9 subtypes have the most zoonotic potential. Captive birds in zoos and safari parks are used for educational, recreational, breeding, and conservational purposes in Bangladesh. To screen for AIV in captive birds to assess potential public health threats, we conducted a cross-sectional study in two safari parks and one zoo in Bangladesh for four months, from November to December 2013 and from January to February 2014. We collected blood samples, oropharyngeal, and cloacal swabs from 228 birds. We tested serum samples for AIV antibodies using competitive enzyme-linked immunosorbent assay (c-ELISA) and AIV sero-subtype H5, H7, and H9 using hemagglutination inhibition (HI) test. Swab samples were tested for the presence of avian influenza viral RNA using real-time reverse transcription-polymerase chain reaction (rRT-PCR). Across all the samples, AIV antibody prevalence was 9.7% (95% CI: 6.1-14.2, n = 228) and AIV HA subtype H5, H7 and H9 sero-prevalence was 0% (95% CI: 0-1.6, n = 228), 0% (95% CI: 0-1.6, n = 228) and 6.6% (95% CI: 3.72-10.6, n = 228), respectively. No AI viral RNA (M-gene) was detected in any swab sample (0%, 95% CI: 0-1.6, n = 228). Birds in the Safari park at Cox's Bazar had a higher prevalence in both AIV antibody prevalence (13.5%) and AIV H9 sero-prevalence (9.6%) than any of the other sites, although the difference was not statistically significant. Among eight species of birds, Emu (Dromaius novaehollandiae) had the highest sero-positivity for both AIV antibody prevalence (26.1%) and AIV H9 prevalence (17.4%) followed by Golden pheasant (Chrysolophus pictus) with AIV antibody prevalence of 18.2% and AIV H9 prevalence of 11.4%. Our results highlight the presence of AI antibodies indicating low pathogenic AIV mingling in captive birds in zoos and safari parks in Bangladesh. Continuous programmed surveillance is therefore recommended to help better understand the diversity of AIVs and provide a clear picture of AI in captive wild birds, enabling interventions to reduce the risk of AIV transmission to humans

Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man.

Contains fulltext : 69895.pdf (publisher's version ) (Closed access)Heterozygous mutations in the LMX1B gene cause nail patella syndrome (NPS) that is associated with nail and skeletal malformations, nephropathy, and glaucoma. Previous phenotype studies of Lmx1b null mice revealed dorsal limb and renal anomalies similar to human NPS, which contributed to the identification of heterozygous mutations in this LIM-homeodomain protein LMX1B as the genetic defect responsible for NPS. Despite advanced insight into the role of the Lmx1b transcription factor in a broad range of animal developmental programs, the pathogenic mechanism underlying dominant inheritance of NPS in man remained unclear. Here, we describe for the first time the detection of two entire LMX1B gene deletions and one smaller exonic LMX1B deletion by multiplex ligation-dependent probe amplification (MLPA) in a series of eight unrelated families with classical features of NPS in whom no pathogenic LMX1B mutation was found by sequence analysis. The identification of entire LMX1B deletions strongly confirms that haploinsufficiency is the principal pathogenetic mechanism of NPS and suggests a difference in dosage sensitivity for this gene between mice and man

Trojan-Like Internalization of Anatase Titanium Dioxide Nanoparticles by Human Osteoblast Cells

Dentistry and orthopedics are undergoing a revolution in order to provide more reliable, comfortable and long-lasting implants to patients. Titanium (Ti) and titanium alloys have been used in dental implants and total hip arthroplasty due to their excellent biocompatibility. However, Ti-based implants in human body suffer surface degradation (corrosion and wear) resulting in the release of metallic ions and solid wear debris (mainly titanium dioxide) leading to peri-implant inflammatory reactions. Unfortunately, our current understanding of the biological interactions with titanium dioxide nanoparticles is still very limited. Taking this into consideration, this study focuses on the internalization of titanium dioxide nanoparticles on primary bone cells, exploring the events occurring at the nano-bio interface. For the first time, we report the selective binding of calcium (Ca), phosphorous (P) and proteins from cell culture medium to anatase nanoparticles that are extremely important for nanoparticle internalization and bone cells survival. In the intricate biological environment, anatase nanoparticles form bio-complexes (mixture of proteins and ions) which act as a kind of ‘Trojan-horse’ internalization by cells. Furthermore, anatase nanoparticles-induced modifications on cell behavior (viability and internalization) could be understand in detail. The results presented in this report can inspire new strategies for the use of titanium dioxide nanoparticles in several regeneration therapies