DNA barcoding reveals both known and novel taxa in the Albitarsis Group (Anopheles: Nyssorhynchus) of Neotropical malaria vectors

<p>Abstract</p> <p>Background</p> <p>Mosquitoes belonging to the Albitarsis Group (<it>Anopheles</it>: <it>Nyssorhynchus</it>) are of importance as malaria vectors across the Neotropics. The Group currently comprises six known species, and recent studies have indicated further hidden biodiversity within the Group. DNA barcoding has been proposed as a highly useful tool for species recognition, although its discriminatory utility has not been verified in closely related taxa across a wide geographic distribution.</p> <p>Methods</p> <p>DNA barcodes (658 bp of the mtDNA <it>Cytochrome c Oxidase </it>- <it>COI</it>) were generated for 565 <it>An. albitarsis </it>s.l. collected in Argentina, Brazil, Colombia, Paraguay, Trinidad and Venezuela over the past twenty years, including specimens from type series and type localities. Here we test the utility of currently advocated barcoding methodologies, including the Kimura-two-parameter distance model (K2P) and Neighbor-joining analysis (NJ), for determining species delineation within mosquitoes of the Neotropical Albitarsis Group of malaria vectors (<it>Anopheles</it>: <it>Nyssorhynchus</it>), and compare results with Bayesian analysis.</p> <p>Results</p> <p>Species delineation through barcoding analysis and Bayesian phylogenetic analysis, fully concur. Analysis of 565 sequences (302 unique haplotypes) resolved nine NJ tree clusters, with less than 2% intra-node variation. Mean intra-specific variation (K2P) was 0.009 (range 0.002 - 0.014), whereas mean inter-specific divergence were several-fold higher at 0.041 (0.020 - 0.056), supporting the reported "barcoding gap". These results show full support for separate species status of the six known species in the Albitarsis Group (<it>An. albitarsis </it>s.s., <it>An. albitarsis </it>F, <it>An. deaneorum</it>, <it>An. janconnae</it>, <it>An. marajoara </it>and <it>An. oryzalimnetes</it>), and also support species level status for two previously detected lineages - <it>An. albitarsis </it>G &<it>An. albitarsis </it>I (designated herein). In addition, we highlight the presence of a unique mitochondrial lineage close to <it>An. deaneorum </it>and <it>An. marajoara </it>(<it>An. albitarsis </it>H) from Rondônia and Mato Grosso in southwestern Brazil. Further integrated studies are required to confirm the status of this lineage.</p> <p>Conclusions</p> <p>DNA barcoding provides a reliable means of identifying both known and undiscovered biodiversity within the closely related taxa of the Albitarsis Group. We advocate its usage in future studies to elucidate the vector competence and respective distributions of all eight species in the Albitarsis Group and the novel mitochondrial lineage (<it>An. albitarsis </it>H) recovered in this study.</p

Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT) for the diagnosis of immune-mediated haemolytic anaemia (IMHA).</p> <p>Methods</p> <p>Canine (n = 247) and feline (n = 74) blood samples were submitted for DAT testing to two laboratories. A subset of canine samples was categorized as having idiopathic IMHA, secondary IMHA, or no IMHA.</p> <p>Results</p> <p>The kappa values for agreement between the tests were in one laboratory 0.86 for canine and 0.58 for feline samples, and in the other 0.48 for canine samples. The lower agreement in the second laboratory was caused by a high number of positive canine DATs for which the gel test was negative. This group included significantly more dogs with secondary IMHA.</p> <p>Conclusions</p> <p>The gel test might be used as a screening test for idiopathic IMHA and is less often positive in secondary IMHA than the DAT.</p

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Current treatment practice of Guillain-Barré syndrome

Objective: To define the current treatment practice of Guillain-Barré syndrome (GBS). Methods: The study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account. Results: We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE. Conclusions: In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Hick and Radhakrishnan on Religious Diversity: Back to the Kantian Noumenon

We shall examine some conceptual tensions in Hick’s ‘pluralism’ in the light of S. Radhakrishnan’s reformulation of classical Advaita. Hick himself often quoted Radhakrishnan’s translations from the Hindu scriptures in support of his own claims about divine ineffability, transformative experience and religious pluralism. However, while Hick developed these themes partly through an adaptation of Kantian epistemology, Radhakrishnan derived them ultimately from Śaṁkara (c.800 CE), and these two distinctive points of origin lead to somewhat different types of reconstruction of the diversity of world religions. Our argument will highlight the point that Radhakrishnan is not a ‘pluralist’ in terms of Hick’s understanding of the Real. The Advaitin ultimate, while it too like Hick’s Real cannot be encapsulated by human categories, is, however, not strongly ineffable, because some substantive descriptions, according to the Advaitic tradition, are more accurate than others. Our comparative analysis will reveal that they differ because they are located in two somewhat divergent metaphysical schemes. In turn, we will be able to revisit, through this dialogue between Hick and Radhakrishnan, the intensely vexed question of whether Hick’s version of pluralism is in fact a form of covert exclusivism.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11841-015-0459-

Improving biomass production and saccharification in Brachypodium distachyon through overexpression of a sucrose-phosphate synthase from sugarcane

The substitution of fossil by renewable energy sources is a major strategy in reducing CO2 emission and mitigating climate change. In the transport sector, which is still mainly dependent on liquid fuels, the production of second generation ethanol from lignocellulosic feedstock is a promising strategy to substitute fossil fuels. The main prerequisites on designated crops for increased biomass production are high biomass yield and optimized saccharification for subsequent use in fermentation processes. We tried to address these traits by the overexpression of a sucrose-phosphate synthase gene (SoSPS) from sugarcane (Saccharum officinarum) in the model grass Brachypodium distachyon. The resulting transgenic B. distachyon lines not only revealed increased plant height at early growth stages but also higher biomass yield from fully senesced plants, which was increased up to 52 % compared to wild-type. Additionally, we determined higher sucrose content in senesced leaf biomass from the transgenic lines, which correlated with improved biomass saccharification after conventional thermo-chemical pretreatment and enzymatic hydrolysis. Combining increased biomass production and saccharification efficiency in the generated B. distachyon SoSPS overexpression lines, we obtained a maximum of 74 % increase in glucose release per plant compared to wild-type. Therefore, we consider SoSPS overexpression as a promising approach in molecular breeding of energy crops for optimizing yields of biomass and its utilization in second generation biofuel production

Drosophila Dynein Intermediate Chain Gene, Dic61B, Is Required for Spermatogenesis

This study reports the identification and characterization of a novel gene, Dic61B, required for male fertility in Drosophila. Complementation mapping of a novel male sterile mutation, ms21, isolated in our lab revealed it to be allelic to CG7051 at 61B1 cytogenetic region, since two piggyBac insertion alleles, CG7051c05439 and CG7051f07138 failed to complement. CG7051 putatively encodes a Dynein intermediate chain. All three mutants, ms21, CG7051c05439 and CG7051f07138, exhibited absolute recessive male sterility with abnormally coiled sperm axonemes causing faulty sperm individualization as revealed by Phalloidin staining in Don Juan-GFP background. Sequencing of PCR amplicons uncovered two point mutations in ms21 allele and confirmed the piggyBac insertions in CG7051c05439 and CG7051f07138 alleles to be in 5′UTR and 4th exon of CG7051 respectively, excision of which reverted the male sterility. In situ hybridization to polytene chromosomes demonstrated CG7051 to be a single copy gene. RT-PCR of testis RNA revealed defective splicing of the CG7051 transcripts in mutants. Interestingly, expression of cytoplasmic dynein intermediate chain, α, β, γ tubulins and α-spectrin was normal in mutants while ultra structural studies revealed defects in the assembly of sperm axonemes. Bioinformatics further highlighted the homology of CG7051 to axonemal dynein intermediate chain of various organisms, including DNAI1 of humans, mutations in which lead to male sterility due to immotile sperms. Based on these observations we conclude that CG7051 encodes a novel axonemal dynein intermediate chain essential for male fertility in Drosophila and rename it as Dic61B. This is the first axonemal Dic gene of Drosophila to be characterized at molecular level and shown to be required for spermatogenesis

Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types