The nasal cavity microbiota of healthy adults

Abstract Background The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. Results We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity. Conclusions There are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities.http://deepblue.lib.umich.edu/bitstream/2027.42/109547/1/40168_2014_Article_56.pd

Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution

The cancer immunoediting hypothesis assumes the immune system sculpts the cancer genome. Here the authors show, in a mouse model, that neutral evolution outweighs the effects of immunoselection and that immune checkpoint blockade potentiates the immunoediting, switching the system to non-neutral evolution

Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins

The cell envelope of mycobacteria, a group of Gram positive bacteria, is composed of a plasma membrane and a Gram-negative-like outer membrane containing mycolic acids. In addition, the surface of the mycobacteria is coated with an ill-characterized layer of extractable, non-covalently linked glycans, lipids and proteins, collectively known as the capsule, whose occurrence is a matter of debate. By using plunge freezing cryo-electron microscopy technique, we were able to show that pathogenic mycobacteria produce a thick capsule, only present when the cells were grown under unperturbed conditions and easily removed by mild detergents. This detergent-labile capsule layer contains arabinomannan, α-glucan and oligomannosyl-capped glycolipids. Further immunogenic and proteomic analyses revealed that Mycobacterium marinum capsule contains high amounts of proteins that are secreted via the ESX-1 pathway. Finally, cell infection experiments demonstrated the importance of the capsule for binding to cells and dampening of pro-inflammatory cytokine response. Together, these results show a direct visualization of the mycobacterial capsular layer as a labile structure that contains ESX-1-secreted proteins

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

ICAR: endoscopic skull‐base surgery

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International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Solution of Airier-stokes Equations on Flowsolver Using Concurrent/Parallel Algorithm

The Havier-Stokes Equations have been solved on the Flowsolver Mk1 concurrent/parallel computer built at HAL. The computation of Axisymmetric laminar Jet impingement on a plane has been selected as the model problem. The computational domain has been divided into four parts and each processing element computes in its assigned domain. The 1 computation by,;these processing elements are synchronized and the data at the boundaries of the subdomains are exchanged at the end of each iteration. This problem could not have been solved an a single processor due to inadequacy of memo-y j availability on--a single processor

SUPERCONDUCTING AND MAGNETIC-PROPERTIES OF TLSR2CA(1-X)R(X)CU(2)O(7) [R=PR,TB]

The magnetic and superconducting properties of the TISr<SUB>2</SUB>Ca<SUB>1&#8722;x</SUB>R<SUB>x</SUB>Cu<SUB>2</SUB>O<SUB>7</SUB> [R=Pr (x=0.2-1.0); Tb (x=0.6 and 1.0)] system are reported. The observation of superconductivity in TISr<SUB>2</SUB>Ca<SUB>0.4</SUB>Pr<SUB>0.6</SUB>Cu<SUB>2</SUB>O<SUB>7 </SUB>(T<SUB>c</SUB>=74 K) suggests that the Pr ions are in the trivalent state. The value of the effective magnetic moment, &#181;<SUB>eff</SUB>=3.15&#181;<SUB>B</SUB>, for the TISr<SUB>2</SUB>Ca<SUB>0.4</SUB>Pr<SUB>0.6</SUB>Cu<SUB>2</SUB>O<SUB>7</SUB> compound, lies between the free-ion values expected for Pr<SUP>3+</SUP> (3.58 &#181;<SUB>B</SUB>) and Pr<SUP>4+</SUP> (2.54&#181;<SUB>B</SUB>). The reduced value of &#181;<SUB>eff</SUB> for the Pr<SUP>3+</SUP> ion is explained in terms of crystal-field effects. For TISr<SUB>2</SUB>TbCu<SUB>2</SUB>O<SUB>7</SUB>, the Tb magnetic moments order antiferromagnetically at 7.0 K, which is the highest magnetic ordering temperature among the known Tb-containing high-T<SUB>c</SUB> related compounds. Superconductivity (T<SUB>c</SUB>=74 and 62 K) and antiferromagnetic ordering (T<SUB>N</SUB>=5 and 6.2 K) coexist in TISr<SUB>2</SUB>Ca<SUB>0.4</SUB>R<SUB>0.6</SUB>Cu<SUB>2</SUB>O<SUB>7</SUB> with R=Pr and Tb, respectively