The Strife is O\u27er, The Battle Won: SATB Choir and Band

Choir and band arrangement, including parts for choir, flute 1-2, oboe, clarinet 1-3, bass clarinet, contra bass clarinet, bassoon, alto saxophone 1-2, B flat tenor saxophone, E flat baritone saxophone, trumpet 1-2, French horn 1-2, baritone bass clef, trombone 1-2, tuba and timpani; 35 pages

Emergence of methicillin resistance predates the clinical use of antibiotics

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics(1). Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two beta-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development

Emergence of methicillin resistance predates the clinical use of antibiotics.

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development

Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia.

Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL

Primers and TaqMan probes used to identify canonical single-nucleotide polymorphisms (canSNPs) that define the two major host-associated <i>S</i>. <i>aureus</i> CC398 clades.

a<p>TaqMan probes for the specific allele of the two canSNP states (underlined) were fluorescently labeled with either 6-FAM or VIC dye.</p>b<p>The genomic position was mapped to the chromosome (genes) of <i>S</i>. <i>aureus</i> CC398 strain SO385 (GenBank accession no. AM990992).</p

Maximum-parsimony tree of 89 <i>S. aureus</i> CC398 isolates based on 4,238 total SNPs, including 1,102 parsimony-informative SNPs.

<p>The bracket highlights the ancient human clade and the newly evolved livestock clade. Arrows indicate the position of the branch used to identify canSNPs, and isolates with unique <i>scn</i> and <i>tet</i>(M) patterns not consistent with the archetypal patterns are highlighted. The figure was adapted from Price <i>et al</i>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079645#pone.0079645-Price1" target="_blank">[3]</a>.</p

List of bi-allelic, non-synonymous canonical single-nucleotide polymorphisms (canSNPs) that define the two major host-associated <i>S. aureus</i> CC398 clades.

a<p>canSNPs used in the study are underlined.</p>b<p>The genomic position was mapped to the chromosome (genes) of <i>S</i>. <i>aureus</i> CC398 reference strain SO385 (GenBank accession no. AM990992).</p

Rapid Differentiation between Livestock-Associated and Livestock-Independent Staphylococcus aureus CC398 Clades

Staphylococcus aureus clonal complex 398 (CC398) isolates cluster into two distinct phylogenetic clades based on single-nucleotide polymorphisms (SNPs) revealing a basal human clade and a more derived livestock clade. The scn and tet(M) genes are strongly associated with the human and the livestock clade, respectively, due to loss and acquisition of mobile genetic elements. We present canonical single-nucleotide polymorphism (canSNP) assays that differentiate the two major host-associated S. aureus CC398 clades and a duplex PCR assay for detection of scn and tet (M). The canSNP assays correctly placed 88 S. aureus CC398 isolates from a reference collection into the human and livestock clades and the duplex PCR assay correctly identified scn and tet(M). The assays were successfully applied to a geographically diverse collection of 272 human S. aureus CC398 isolates. The simple assays described here generate signals comparable to a whole-genome phylogeny for major clade assignment and are easily integrated into S. aureus CC398 surveillance programs and epidemiological studies. © 2013 Stegger et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe