10 research outputs found

    Establishment of the nasal microbiota in the first 18 months of life: Correlation with early-onset rhinitis and wheezing.

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    BACKGROUND: Dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and susceptibility to childhood respiratory disorders. OBJECTIVE: The aim of this case-control study was to monitor, evaluate, and compare development of the nasal microbiota of infants with rhinitis and wheeze in the first 18 months of life with those of healthy control subjects. METHODS: Anterior nasal swabs of 122 subjects belonging to the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were collected longitudinally over 7 time points in the first 18 months of life. Nasal microbiota signatures were analyzed by using 16S rRNA multiplexed pair-end sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2) patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control subjects (n = 60). RESULTS: Maturation of the nasal microbiome followed distinctive patterns in infants from both rhinitis groups compared with control subjects. Bacterial diversity increased over the period of 18 months of life in control infants, whereas infants with rhinitis showed a decreasing trend (P < .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family (Actinobacteria phylum) and early colonization with the Staphylococcaceae family (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects (adjusted P < .05). The only difference between the rhinitis and control groups was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05). Determinants of nasal microbiota succession included sex, mode of delivery, presence of siblings, and infant care attendance. CONCLUSION: Our results support the hypothesis that the nasal microbiome is involved in development of early-onset rhinitis and wheeze in infants

    Atomic insights of an up and down conformation of the Acinetobacter baumannii F₁-ATPase subunit ε and deciphering the residues critical for ATP hydrolysis inhibition and ATP synthesis

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    The Acinetobacter baumannii F1 FO -ATP synthase (α3 :β3 :γ:δ:ε:a:b2 :c10 ), which is essential for this strictly respiratory opportunistic human pathogen, is incapable of ATP-driven proton translocation due to its latent ATPase activity. Here, we generated and purified the first recombinant A. baumannii F1 -ATPase (AbF1 -ATPase) composed of subunits α3 :β3 :γ:ε, showing latent ATP hydrolysis. A 3.0 Å cryo-electron microscopy structure visualizes the architecture and regulatory element of this enzyme, in which the C-terminal domain of subunit ε (Abε) is present in an extended position. An ε-free AbF1 -ɑβγ complex generated showed a 21.5-fold ATP hydrolysis increase, demonstrating that Abε is the major regulator of AbF1 -ATPase's latent ATP hydrolysis. The recombinant system enabled mutational studies of single amino acid substitutions within Abε or its interacting subunits β and γ, respectively, as well as C-terminal truncated mutants of Abε, providing a detailed picture of Abε's main element for the self-inhibition mechanism of ATP hydrolysis. Using a heterologous expression system, the importance of Abε's C-terminus in ATP synthesis of inverted membrane vesicles, including AbF1 FO -ATP synthases, has been explored. In addition, we are presenting the first NMR solution structure of the compact form of Abε, revealing interaction of its N-terminal β-barrel and C-terminal ɑ-hairpin domain. A double mutant of Abε highlights critical residues for Abε's domain-domain formation which is important also for AbF1 -ATPase's stability. Abε does not bind MgATP, which is described to regulate the up and down movements in other bacterial counterparts. The data are compared to regulatory elements of F1 -ATPases in bacteria, chloroplasts, and mitochondria to prevent wasting of ATP.Ministry of Education (MOE)Nanyang Technological UniversityResearch reported in this publication is supported by the Singapore Ministry of Education Academic Research Fund Tier 1 (RG20/22) to G.G. The PhD scholarship of Khoa Le Cong Minh was supported by a Vingroup-NTU graduate scholarship

    Abstracts from the 8th International Congress of the Asia Pacific Society of Infection Control (APSIC)

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    A wavelet algorithm for the solution of the double layer potential equation over polygonal boundaries

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    In this paper we consider a piecewise linear collocation method for the solution of the double layer potential equation corresponding to Laplace's equation over polygonal domains. We give a wavelet algorithm for the computation of the corresponding stiffness matrix and for the solution of the arising matrix equation with no more than O(N x [logN]&quot;8) arithmetic operations. The error of the resulting approximate solution is of order O(N&quot;-&quot;2 x [logN]&quot;6). Finally, we give some remarks on the generalization of the algorithm to the piecewise cubic collocation and present numerical tests. (orig.)Available from TIB Hannover: RR 5549(106)+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

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    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to 5.0 × 10 -21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10 -6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

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