A unique bacteriohopanetetrol stereoisomer of marine anammox

Anaerobic ammonium oxidation (anammox) is a major process of bioavailable nitrogen removal from marine systems. Previously, a bacteriohopanetetrol (BHT) isomer, with unknown stereochemistry, eluting later than BHT using high performance liquid chromatography (HPLC), was detected in ‘Ca. Scalindua profunda’ and proposed as a biomarker for anammox in marine paleo-environments. However, the utility of this BHT isomer as an anammox biomarker is hindered by the fact that four other, non-anammox bacteria are also known to produce a late-eluting BHT stereoisomer. The stereochemistry in Acetobacter pasteurianus, Komagataeibacter xylinus and Frankia sp. was known to be 17β, 21β(H), 22R, 32R, 33R, 34R (BHT-34R). The stereochemistry of the late-eluting BHT in Methylocella palustris was unknown. To determine if marine anammox bacteria produce a unique BHT isomer, we studied the BHT distributions and stereochemistry of known BHT isomer producers and of previously unscreened marine (‘Ca. Scalindua brodeae’) and freshwater (‘Ca. Brocadia sp.’) anammox bacteria using HPLC and gas chromatographic (GC) analysis of acetylated BHTs and ultra high performance liquid chromatography (UHPLC)-high resolution mass spectrometry (HRMS) analysis of non-acetylated BHTs. The 34R stereochemistry was confirmed for the BHT isomers in Ca. Brocadia sp. and Methylocella palustris. However, ‘Ca. Scalindua sp.’ synthesise a stereochemically distinct BHT isomer, with still unconfirmed stereochemistry (BHT-x). Only GC analysis of acetylated BHT and UHPLC analysis of non-acetylated BHT distinguished between late-eluting BHT isomers. Acetylated BHT-x and BHT-34R co-elute by HPLC. As BHT-x is currently only known to be produced by ‘Ca. Scalindua spp.’, it may be a biomarker for marine anammox

The paleolimnologist's guide to compound-specific stable isotope analysis - An introduction to principles and applications of CSIA for quaternary lake sediments

The stable isotope composition of key chemical elements for life on Earth (e.g., carbon, hydrogen, nitrogen, oxygen, sulfur) tracks changes in fluxes and turnover of these elements in the biogeosphere. Over the past 15-20 years, the potential to measure these isotopic compositions for individual, source-specific organic molecules (biomarkers) and to link them to a range of environmental conditions and processes has been unlocked and amplified by increasingly sensitive, affordable and wide-spread analytical technology. Paleoenvironmental research has seen enormous step-changes in our understanding of past ecosystem dynamics. Vital to these paradigm shifts is the need for well-constrained modern and recent analogues. Through increased understanding of these environments and their biological pathways we can successfully unravel past climatic changes and associated ecosystem adaption. With this review, we aim to introduce scientists working in the field of Quaternary paleolimnology to the tools that compound-specific isotope analysis (CSIA) provides for the gain of information on biogeochemical conditions in ancient environments. We provide information on fundamental principles and applications of novel and established CSIA applications based on the carbon, hydrogen, nitrogen, oxygen and sulfur isotopic composition of biomarkers. While biosynthesis, sources and associated isotope fractionation patterns of compounds such as n-alkanes are relatively well-constrained, new applications emerge from the increasing use of functionalized alkyl lipids, steroids, hopanoids, isoprenoids, GDGTs, pigments or cellulose. Biosynthesis and fractionation are not always fully understood

Dark CO2 fixation into phospholipid-derived fatty acids by the cold-water coral associated sponge Hymedesmia (Stylopus) coriacea (Tisler Reef, NE Skagerrak)

Many cold-water sponges harbour microorganisms of which the role in the sponge host remains enigmatic. Here, we show a transfer of fixed inorganic carbon by sponge-associated microbes to its host, the cold-water coral encrusting sponge Hymedesmia (Stylopus) coriacea. Sponge were collected at approx. 100 m depth and incubated for 1.5–2.5 days with 13C labelled dissolved inorganic carbon (DIC) as tracer. Total DIC fixation rates ranged from 0.03–0.11 mmol C × mmol Csponge × d−1. 13C-tracer was recovered in bacterial-specific (i.e. short and branched) and sponge-specific (very long-chained) phospholipid-derived fatty acids (PLFA's), but was not incorporated into archaeal lipids. 13C-incorporation in biomarkers such as C16:1w7c and C18:1w7c indicated that nitrifying and/or sulphur-oxidizing bacteria (chemoautotrophs) were likely active in the sponge. Trophic transfer of microbially-fixed carbon to the sponge host was confirmed by recovery of label in very long chain fatty acids (VLCFA's) including C26:2 and C26:3. Tracer accumulation into several VLCFA's continued after removal of 13C-DIC, while tracer in most bacteria-specific PLFA's declined, indicating a transfer and elongation of bacterial-specific PLFA's to sponge-specific PLFA's. This implies that PLFA precursors released from chemo- as well as heterotrophic microbes in sponges contributed to the synthesis of VLCFA's, identifying sponge-associated bacteria as symbionts of the sponge

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project.

Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests. All the data are now available through EuroPhenome database (www.europhenome.org) and the WTSI mouse portal (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are available through the European Mouse Mutant Archive (EMMA), the International Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP) Repository. Overall conclusions from both studies converged, with at least one phenotype scored in at least 80% of the mutant lines. In addition, 57% of the lines were viable, 13% subviable, 30% embryonic lethal, and 7% displayed fertility impairments. These efforts provide an important underpinning for a future global programme that will undertake the complete functional annotation of the mammalian genome in the mouse model

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

Cold spells in the Nordic Seas during the early Eocene Greenhouse

Abstract The early Eocene (c. 56 - 48 million years ago) experienced some of the highest global temperatures in Earth’s history since the Mesozoic, with no polar ice. Reports of contradictory ice-rafted erratics and cold water glendonites in the higher latitudes have been largely dismissed due to ambiguity of the significance of these purported cold-climate indicators. Here we apply clumped isotope paleothermometry to a traditionally qualitative abiotic proxy, glendonite calcite, to generate quantitative temperature estimates for northern mid-latitude bottom waters. Our data show that the glendonites of the Danish Basin formed in waters below 5 °C, at water depths of &lt;300 m. Such near-freezing temperatures have not previously been reconstructed from proxy data for anywhere on the early Eocene Earth, and these data therefore suggest that regionalised cool episodes punctuated the background warmth of the early Eocene, likely linked to eruptive phases of the North Atlantic Igneous Province.</jats:p

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015