Encoding of conditioned fear in central amygdala inhibitory circuits

The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that neuronal activity in the lateral subdivision of the central amygdala (CEl) is required for fear acquisition, whereas conditioned fear responses are driven by output neurons in the medial subdivision (CEm). Functional circuit analysis revealed that inhibitory CEA microcircuits are highly organized and that cell-type-specific plasticity of phasic and tonic activity in the CEl to CEm pathway may gate fear expression and regulate fear generalization. Our results define the functional architecture of CEA microcircuits and their role in the acquisition and regulation of conditioned fear behaviour.     

Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites

The elongation cycle of protein synthesis involves the delivery of aminoacyl-transfer RNAs to the aminoacyl-tRNA-binding site (A?site) of the ribosome, followed by peptide-bond formation and translocation of the tRNAs through the ribosome to reopen the A?site. The translocation reaction is catalysed by elongation factor G (EF-G) in a GTP-dependent manner. Despite the availability of structures of various EF-G-ribosome complexes, the precise mechanism by which tRNAs move through the ribosome still remains unclear. Here we use multiparticle cryoelectron microscopy analysis to resolve two previously unseen subpopulations within Thermus thermophilus EF-G-ribosome complexes at subnanometre resolution, one of them with a partly translocated tRNA. Comparison of these substates reveals that translocation of tRNA on the 30S subunit parallels the swivelling of the 30S head and is coupled to unratcheting of the 30S body. Because the tRNA maintains contact with the peptidyl-tRNA-binding site (P?site) on the 30S head and simultaneously establishes interaction with the exit site (E?site) on the 30S platform, a novel intra-subunit 'pe/E' hybrid state is formed. This state is stabilized by domain?IV of EF-G, which interacts with the swivelled 30S-head conformation. These findings provide direct structural and mechanistic insight into the 'missing link' in terms of tRNA intermediates involved in the universally conserved translocation process.     

Broad phylogenomic sampling improves resolution of the animal tree of life

Long-held ideas regarding the evolutionary relationships among animals have recently been upended by sometimes controversial hypotheses based largely on insights from molecular data. These new hypotheses include a clade of moulting animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs and annelids (Lophotrochozoa). Many relationships remain disputed, including those that are required to polarize key features of character evolution, and support for deep nodes is often low. Phylogenomic approaches, which use data from many genes, have shown promise for resolving deep animal relationships, but are hindered by a lack of data from many important groups. Here we report a total of 39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla, including 11 phyla previously lacking genomic or expressed-sequence-tag data. Analysed in combination with existing sequences, our data reinforce several previously identified clades that split deeply in the animal tree (including Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data (such as velvet worms rather than tardigrades as the sister group of arthropods), and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists. In addition, we find strong support for several new hypotheses. These include a clade that unites annelids (including sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs as sister to that assemblage, and the placement of ctenophores as the earliest diverging extant multicellular animals. A single origin of spiral cleavage (with subsequent losses) is inferred from well-supported nodes. Many relationships between a stable subset of taxa find strong support, and a diminishing number of lineages remain recalcitrant to placement on the tree.     

A choice-semantical approach to theoretical truth

A central topic in the logic of science concerns the proper semantic analysis of theoretical sentences, that is sentences containing theoretical terms. In this paper, we present a novel choice-semantical account of theoretical truth based on the epsilon-term definition of theoretical terms. Specifically, we develop two ways of specifying the truth conditions of theoretical statements in a choice functional semantics, each giving rise to a corresponding logic of such statements. In order to investigate the inferential strength of these logical systems, we provide a translation of each truth definition into a modal definition of theoretical truth. Based on this, we show that the stronger notion of choice-semantical truth captures more adequately our informal semantic understanding of scientific statements.     

Microstructure and physical properties of steel-ladle purging plug refractory materials

Three different castables were prepared as steel-ladle purging-plug refractory materials:corundum-based low-cement castable (C-LCC), corundum-spinel-based low-cement castable (C-S-LCC), and no-cement corundum-spinel castable (C-S-NCC) (hydratable alumina ρ-Al₂O₃ bonded). The properties of these castables were characterized with regard to water demand/flow ability, cold crushing strength (CCS), cold modulus of rupture (CMoR), permanent linear change (PLC), apparent porosity, and hot modulus of rupture (HMoR). The results show the CCS/CMoR and HMoR of C-LCC and C-S-LCC are greater than those of the castable C-S-NCC. According to the microstructure analysis, the sintering effect and the bonding type of the matrix material differ among the three castables. The calcium hexaluminate (CA₆) phase in the matrix of C-LCC enhances the cold and hot mechanical strengths. In the case of C-S-LCC, the CA₆ and 2CaO·2MgO·14Al₂O₃ (C₂M₂A₁₄) ternary phases generated from the matrix can greatly increase the cold and hot mechanical strengths. In the case of the no-cement castable, sintering becomes difficult, resulting in a lower mechanical strength.     

Decline of the marine ecosystem caused by a reduction in the Atlantic overturning circulation

Reorganizations of the Atlantic meridional overturning circulation were associated with large and abrupt climatic changes in the North Atlantic region during the last glacial period. Projections with climate models suggest that similar reorganizations may also occur in response to anthropogenic global warming. Here I use ensemble simulations with a coupled climate-ecosystem model of intermediate complexity to investigate the possible consequences of such disturbances to the marine ecosystem. In the simulations, a disruption of the Atlantic meridional overturning circulation leads to a collapse of the North Atlantic plankton stocks to less than half of their initial biomass, owing to rapid shoaling of winter mixed layers and their associated separation from the deep ocean nutrient reservoir. Globally integrated export production declines by more than 20 per cent owing to reduced upwelling of nutrient-rich deep water and gradual depletion of upper ocean nutrient concentrations. These model results are consistent with the available high-resolution palaeorecord, and suggest that global ocean productivity is sensitive to changes in the Atlantic meridional overturning circulation.