Novel Mutation in Boy With Cartilage-hair Hypoplasia

BackgroundCartilage-hair hypoplasia (MIM 250250) is an autosomal recessive disease with diverse clinical manifestations. The clinical phenotypes include variable degrees of bone and hair dysplasia, deficient cellular and/or humoral immunity, and a predisposition to malignancy.MethodsWe performed genetic studies of a patient with disproportionate short stature and brittle scalp hair. Genetic studies were also carried out in the patient's parents.ResultsA novel maternal mutation that consisted of a duplication of 14 nucleotides at position −13 of the RNA component of the RNA component of mitochondrial RNA processing endoribonuclease gene (RMRP; g. −26 to −13 dupTACTACTCTGTGAA, promoter region) and a paternal mutation base substitution of C to T at nucleotide + 230 (designated as + 1 in the transcription initiation site) in the coding sequence of RMRP were detected in this patient.ConclusionA novel maternal RMRP mutation was found in a Chinese boy with typical cartilage-hair hypoplasia

ESL Club & Women Speak: Our Second Home in America

SWOSU ESL Club Newsletter: Fall 2017 is the third issue of the newsletter for the English as a Second Language Club (ESL).https://dc.swosu.edu/esl/1002/thumbnail.jp

Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA

Indolicidin, a l3-residue antimicrobial peptide-amide, which is unusually rich in tryptophan and proline, is isolated from the cytoplasmic granules of bovine neutrophils. In this study, the structures of indolicidin in 50% D(3)-trifluoroethanol and in the absence and presence of SDS and D(38)-dodecylphosphocholine were determined using NMR spectroscopy. Multiple conformations were found and were shown to be due to different combinations of contact between the two WPW motifs. Although indolicidin is bactericidal and able to permeabilize bacterial membranes, it does not lead to cell wall lysis, showing that there is more than one mechanism of antimicrobial action. The structure of indolicidin in aqueous solution was a globular and amphipathic conformation, differing from the wedge shape adopted in lipid micelles, and these two structures were predicted to have different functions. Indolicidin, which is known to inhibit DNA synthesis and induce filamentation of bacteria, was shown to bind DNA in gel retardation and fluorescence quenching experiments. Further investigations using surface plasmon resonance confirmed the DNA-binding ability and showed the sequence preference of indolicidin. Based on our biophysical studies and previous results, we present a diagram illustrating the DNA-binding mechanism of the antimicrobial action of indolicidin and explaining the roles of the peptide when interacting with lipid bilayers at different concentrations

Suppressor of K+ transport growth defect 1 (SKD1) interactswith RING-type ubiquitin ligase and sucrose non-fermenting1-related protein kinase (SnRK1) in the halophyte ice plant

SKD1 (suppressor of K+ transport growth defect 1) is an AAA-type ATPase that functions as a molecular motor. It was previously shown that SKD1 accumulates in epidermal bladder cells of the halophyte Mesembryanthemum crystallinum. SKD1 knock-down Arabidopsis mutants showed an imbalanced Na+/K+ ratio under salt stress. Two enzymes involved in protein post-translational modifications that physically interacted with McSKD1 were identified. McCPN1 (copine 1), a RING-type ubiquitin ligase, has an N-terminal myristoylation site that links to the plasma membrane, a central copine domain that interacts with McSKD1, and a C-terminal RING domain that catalyses protein ubiquitination. In vitro ubiquitination assay demonstrated that McCPN1 was capable of mediating ubiquitination of McSKD1. McSnRK1 (sucrose non-fermenting 1-related protein kinase) is a Ser/Thr protein kinase that contains an N-terminal STKc catalytic domain to phosphorylate McSKD1, and C-terminal UBA and KA1 domains to interact with McSKD1. The transcript and protein levels of McSnRK1 increased as NaCl concentrations increased. The formation of an SKD1–SnRK1–CPN1 ternary complex was demonstrated by yeast three-hybrid and bimolecular fluorescence complementation. It was found that McSKD1 preferentially interacts with McSnRK1 in the cytosol, and salt induced the re-distribution of McSKD1 and McSnRK1 towards the plasma membrane via the microtubule cytoskeleton and subsequently interacted with RING-type E3 McCPN1. The potential effects of ubiquitination and phosphorylation on McSKD1, such as changes in the ATPase activity and cellular localization, and how they relate to the functions of SKD1 in the maintenance of Na+/K+ homeostasis under salt stress, are discussed

Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells

<p>Abstract</p> <p>Background</p> <p>Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death.</p> <p>Methods</p> <p>Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O₂concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio.</p> <p>Results</p> <p>According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus.</p> <p>Conclusions</p> <p>We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.</p

Novel Interleukin-10 Gene Polymorphism Is Linked to Gestational Diabetes in Taiwanese Population

Objective: The association of interleukin-10 (IL-10) polymorphism with diabetes and its complication was recently established, while there were few researches considering the potential role of IL-10 in gestational diabetes (GDM). This study aimed to investigate the association between IL-10 gene rs1800896 (−1082 A/G), rs1800871 (−819 T/C), rs1800872 (−592 A/C), and rs3021094 (3388 A/C) single nucleotide polymorphisms (SNPs) and GDM susceptibility.Methods: This study included 72 GDM patients and 100 healthy pregnant women. Direct sequencing of the products from polymerase chain reactions of the extracted genomic DNA from study subjects were conducted for analyzing IL-10 gene polymorphism and further genotype frequencies were compared. Plasma IL-10 concentration was measured by ELISA method.Results: The results revealed no significant difference in −592 A/C, −819 T/C, and −1082 A/G genotypes. Significantly increased prevalence of A allele (P = 0.028, OR = 1.69, 95% CI = 1.081–2.64) and A/A genotype (P = 0.031, OR = 2.881, 95% CI = 1.145–7.250) at a previously un-characterized rs3021094 SNP were discovered in the GDM group. Increased IL-10 levels and insulin resistance were also related to the genotype of rs3021094. The risk of GDM was increased when IL-10 level was over 6.5 pg/ml.Conclusion: Our study demonstrated that A allele and A/A genotype of rs3021094 SNP in IL-10 gene were linked to increased risk for GDM, IL-10 plasma level and insulin resistance, which could be potential targets for early screening and detection of GDM

High Prevalence of Mutations in Quinolone-resistance-determining Regions and mtrR Loci in Polyclonal Neisseria gonorrhoeae Isolates at a Tertiary Hospital in Southern Taiwan

Background/PurposeThe emergence of multidrug-resistant Neisseria gonorrhoeae is a great challenge in controlling gonorrhea. This study was conducted to survey the prevalence of molecular mechanisms of antimicrobial resistance among 45 clinical isolates of N. gonorrhoeae collected at a university hospital in Southern Taiwan during 1999-2004.MethodsMutations in mtrR loci and quinolone-resistance-determining regions (QRDRs) were examined by gene sequencing. Polymerase chain reactions with specific primers were performed to detect ermA, ermB, ermC, and ermF. Serogroups and serovars were determined by commercial kits.ResultsThe percentage of multidrug resistance, that is, resistance to penicillin, tetracycline, erythromycin, and ciprofloxacin, among the 45 isolates was 40%. Ceftriaxone and spectinomycin were active against all isolates in vitro. The frequency of mutations in the QRDR and mtrR promoter was 82.2% and 93.3%, respectively. Eighty-two percent of the isolates carried mutations both in the QRDR and mtrR loci. Of nine mutation profiles with QRDR mutations (n =37), gyrA-Ser91Phe/gyrA-Asp95Gly/parC-Ser87Arg was the most common type (56.8%). Acquired genes for rRNA methylase were detected in 11 isolates (10 ermB and 1 ermA). Twenty-seven serovars were identified and all belonged to serogroup B, which suggested that multiple clones of N. gonorrhoeae were circulating in the community in the Tainan area.ConclusionThe high prevalence of multidrug resistance caused by varied resistance mechanisms in N. gonorrhoeae limits the drug choice. Ongoing surveillance of antimicrobial resistance and discovery of new effective antibiotic therapy are warranted in endemic areas