Assignment of Reference 5’-end 16S rDNA Sequences and Species-Specific Sequence Polymorphisms Improves Species Identification of Nocardia

16S rDNA sequence analysis is the most accurate method for definitive species identification of nocardiae. However, conflicting results can be found due to sequence errors in gene databases. This study tested the feasibility of species identification of Nocardia by partial (5’-end 606-bp) 16S rDNA sequencing, based on sequence comparison with “reference” sequences of well-annotated strains. This new approach was evaluated using 96 American Type Culture Collection (n=6), and clinical (n=90) Nocardia isolates. Nucleotide sequence-based polymorphisms within species were indicative of “sequence types” for that species. Sequences were compared with those in the GenBank, Bioinformatics Bacteria Identification and Ribosomal Database Project databases. Compared with the reference sequence set, all 96 isolates were correctly identified using the criterion of ≥99% sequence similarity. Seventy-eight (81.3%) were speciated by database comparison; alignment with reference sequences resolved the identity of 14 (15%) isolates whose sequences yielded 100% similarity to sequences in GenBank under >1 species designation. Of 90 clinical isolates, the commonest species was Nocardia nova (33.3%) followed by Nocardia cyriacigeorgica (26.7%). Recently-described or uncommon species included Nocardia veterana (4.4%), Nocarida bejingensis (2.2%) and, Nocardia abscessus and Nocardia arthriditis (each n=1). Nocardia asteroides sensu stricto was rare (n=1). There were nine sequence types of N. nova, three of Nocardia brasiliensis with two each of N. cyriacigeorgica and Nocardia farcinica. Thirteen novel sequences were identified. Alignment of sequences with reference sequences facilitated species identification of Nocardia and allowed delineation of sequence types within species, suggesting that such a barcoding approach can be clinically useful for identification of bacteria

Molecular Typing of Australian Scedosporium Isolates Showing Genetic Variability and Numerous S. aurantiacum

Molecular typing showed genetic diversity, dismissed 2 suspected outbreaks of scedosporiosis, and identified multiple strains of the newly described species S. aurantiacum

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Successful treatment of Cryptococcus neoformans immune reconstitution inflammatory syndrome in an immunocompetent host using thalidomide

Immune reconstitution inflammatory syndrome (IRIS) can complicate antifungal treatment of cryptococcosis. There are limited data on managing cryptococcal-associated IRIS. We describe an immunocompetent patient who developed IRIS complicating Cryptococcus neoformans meningitis, successfully treated with thalidomide following failure of corticosteroid therapy. Data on thalidomide use in cryptococcal IRIS are awaited

Macromolecular crowding amplifies adipogenesis of human bone marrow-derived mesenchymal stem cells by enhancing the pro-adipogenic microenvironment

10.1089/ten.tea.2013.0337Tissue Engineering - Part A205-6966-98