An index to assess the health and benefits of the global ocean

The ocean plays a critical role in supporting human well-being, from providing food, livelihoods and recreational opportunities to regulating the global climate. Sustainable management aimed at maintaining the flow of a broad range of benefits from the ocean requires a comprehensive and quantitative method to measure and monitor the health of coupled human–ocean systems. We created an index comprising ten diverse public goals for a healthy coupled human–ocean system and calculated the index for every coastal country. Globally, the overall index score was 60 out of 100 (range 36–86), with developed countries generally performing better than developing countries, but with notable exceptions. Only 5% of countries scored higher than 70, whereas 32% scored lower than 50. The index provides a powerful tool to raise public awareness, direct resource management, improve policy and prioritize scientific research.     

The coefficient of variation biplot

This note introduces the coefficient of variation biplot, and suggests that it will provide a useful graphical display of data matrices in which the relative variability of the columns is of interest.The author acknowledges support from the University of Cape Town and the Foundation for Research Development of the Council for Scientific and Industrial Research. J. C. Gower and the referees provided helpful comments.     

Anti-hapten antibodies in the serum and bronchial secretions of dogs following respiratory tract immunization

Zusammenfassung Im Serum und in Bronchialsekreten von Hunden konnten Antikörper gegen DNP, die über die Atmungswege mit DNP-Proteinkonjugaten immunisiert worden waren, nachgewiesen werden. Die Titer der beobachteten spezifischen Antikörper waren für eine detaillierte Analyse zu niedrig.

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This work was supported by National Institutes of Health Training Grant No. 5TI AI0128-09.     

The chronic effects of nicotine monomethidide on gastric secretion in pylorus-ligated rats

Résumé L'action de la nicotine monométhyliodine (NMI) sur la sécrétion gastrique basique et sur les concentrations de choline de cervelles, d'acétylcholine et de nicotine et sur l'activité de la transacétylcholinestérase a été étudiée chez des rats. Le NMI, sel quaternaire de nicotine, qui ne traverse pas la barrière hématoencéphalique, a été administré dans de la gélatine à 6% en dosage sous-cutané de 1000 g/ml/kg/jour pendant 14 jours. Le NMI n'a pas changé de paramètres et aucune trace de nicotine n'a été découverte dans les homogénates de cervelles complètes.     

Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria

We used exome sequencing to identify the genetic basis of combined malonic and methylmalonic aciduria (CMAMMA). We sequenced the exome of an individual with CMAMMA and followed up with sequencing of eight additional affected individuals (cases). This included one individual who was identified and diagnosed by searching an exome database. We identify mutations in ACSF3, encoding a putative methylmalonyl-CoA and malonyl-CoA synthetase as a cause of CMAMMA. We also examined a canine model of CMAMMA, which showed pathogenic mutations in a predicted ACSF3 ortholog. ACSF3 mutant alleles occur with a minor allele frequency of 0.0058 in ～1,000 control individuals, predicting a CMAMMA population incidence of ～1:30,000. ACSF3 deficiency is the first human disorder identified as caused by mutations in a gene encoding a member of the acyl-CoA synthetase family, a diverse group of evolutionarily conserved proteins, and may emerge as one of the more common human metabolic disorders.     

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.     

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.