Extracellular calcium ions modify the effects of Anemonia sulcata toxin (ATX II) in guinea-pig papillary muscles

In isolated guinea-pig papillary muscle ATX II prolonged the action potential duration to a lesser extent at high extracellular Ca++-concentrations. This is interpreted as an interference of Ca++ with ATX II-binding sites.     

Nucleotide sequence of the rat skeletal muscle actin gene

The actins constitute a family of highly conserved proteins found in all eukaryotic cells. Their conservation through a very wide range of taxonomic groups and the existence of tissue-specific isoforms make the actin genes very interesting for the study of the evolution of genes and their controlling elements. On the basis of amino acid sequence data, at least six different mammalian actins have been identified (skeletal muscle, cardiac muscle, two smooth muscle actins and the cytoplasmic beta- and gamma-actins). Rat spleen DNA digested by the EcoRI restriction enzyme contains at least 12 different fragments with actin-like sequences but only one which hybridized, in very stringent conditions, with the skeletal muscle cloned cDNA probe. Here we describe the sequence of the actin gene in that fragment. The nucleotide sequence codes for two amino acids, Met-Cys, preceding the known N-terminal Asp of the mature protein. There are five small introns in the coding region and a large intron in the 5'-untranslated region. Comparison of the structure of the rat skeletal muscle actin gene with available data on actin genes from other organisms shows that while the sequenced actin genes from Drosophila and yeast have introns at different locations, introns located at codons specifying amino acids 41, 121, 204 and 267 have been preserved at least from the echinoderm to the vertebrates. A similar analysis has been done by Davidson. An intron at codon 150 is common to a plant actin gene and the skeletal muscle acting gene.     

Independent evolution of striated muscles in cnidarians and bilaterians

Striated muscles are present in bilaterian animals (for example, vertebrates, insects and annelids) and some non-bilaterian eumetazoans (that is, cnidarians and ctenophores). The considerable ultrastructural similarity of striated muscles between these animal groups is thought to reflect a common evolutionary origin. Here we show that a muscle protein core set, including a type II myosin heavy chain (MyHC) motor protein characteristic of striated muscles in vertebrates, was already present in unicellular organisms before the origin of multicellular animals. Furthermore, 'striated muscle' and 'non-muscle' myhc orthologues are expressed differentially in two sponges, compatible with a functional diversification before the origin of true muscles and the subsequent use of striated muscle MyHC in fast-contracting smooth and striated muscle. Cnidarians and ctenophores possess striated muscle myhc orthologues but lack crucial components of bilaterian striated muscles, such as genes that code for titin and the troponin complex, suggesting the convergent evolution of striated muscles. Consistently, jellyfish orthologues of a shared set of bilaterian Z-disc proteins are not associated with striated muscles, but are instead expressed elsewhere or ubiquitously. The independent evolution of eumetazoan striated muscles through the addition of new proteins to a pre-existing, ancestral contractile apparatus may serve as a model for the evolution of complex animal cell types.     

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.     

Engineering the third wave of biocatalysis

Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.     

Quantum phase transition in a resonant level coupled to interacting leads

A Luttinger liquid is an interacting one-dimensional electronic system, quite distinct from the 'conventional' Fermi liquids formed by interacting electrons in two and three dimensions. Some of the most striking properties of Luttinger liquids are revealed in the process of electron tunnelling. For example, as a function of the applied bias voltage or temperature, the tunnelling current exhibits a non-trivial power-law suppression. (There is no such suppression in a conventional Fermi liquid.) Here, using a carbon nanotube connected to resistive leads, we create a system that emulates tunnelling in a Luttinger liquid, by controlling the interaction of the tunnelling electron with its environment. We further replace a single tunnelling barrier with a double-barrier, resonant-level structure and investigate resonant tunnelling between Luttinger liquids. At low temperatures, we observe perfect transparency of the resonant level embedded in the interacting environment, and the width of the resonance tends to zero. We argue that this behaviour results from many-body physics of interacting electrons, and signals the presence of a quantum phase transition. Given that many parameters, including the interaction strength, can be precisely controlled in our samples, this is an attractive model system for studying quantum critical phenomena in general, with wide-reaching implications for understanding quantum phase transitions in more complex systems, such as cold atoms and strongly correlated bulk materials.     

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.