Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite

From the standpoints of both basic research and biotechnology, there is considerable interest in reaching a clearer understanding of the diversity of biological mechanisms employed during lignocellulose degradation. Globally, termites are an extremely successful group of wood-degrading organisms and are therefore important both for their roles in carbon turnover in the environment and as potential sources of biochemical catalysts for efforts aimed at converting wood into biofuels. Only recently have data supported any direct role for the symbiotic bacteria in the gut of the termite in cellulose and xylan hydrolysis. Here we use a metagenomic analysis of the bacterial community resident in the hindgut paunch of a wood-feeding 'higher' Nasutitermes species (which do not contain cellulose-fermenting protozoa) to show the presence of a large, diverse set of bacterial genes for cellulose and xylan hydrolysis. Many of these genes were expressed in vivo or had cellulase activity in vitro, and further analyses implicate spirochete and fibrobacter species in gut lignocellulose degradation. New insights into other important symbiotic functions including H2 metabolism, CO2-reductive acetogenesis and N2 fixation are also provided by this first system-wide gene analysis of a microbial community specialized towards plant lignocellulose degradation. Our results underscore how complex even a 1-microl environment can be.     

Coupled 142Nd-143Nd evidence for a protracted magma ocean in Mars

Resolving early silicate differentiation timescales is crucial for understanding the chemical evolution and thermal histories of terrestrial planets. Planetary-scale magma oceans are thought to have formed during early stages of differentiation, but the longevity of such magma oceans is poorly constrained. In Mars, the absence of vigorous convection and plate tectonics has limited the scale of compositional mixing within its interior, thus preserving the early stages of planetary differentiation. The SNC (Shergotty-Nakhla-Chassigny) meteorites from Mars retain 'memory' of these events. Here we apply the short-lived 146Sm-142Nd and the long-lived 147Sm-143Nd chronometers to a suite of shergottites to unravel the history of early silicate differentiation in Mars. Our data are best explained by progressive crystallization of a magma ocean with a duration of approximately 100 million years after core formation. This prolonged solidification requires the existence of a primitive thick atmosphere on Mars that reduces the cooling rate of the interior.     

Coherent zero-state and pi-state in an exciton-polariton condensate array

The effect of quantum statistics in quantum gases and liquids results in observable collective properties among many-particle systems. One prime example is Bose-Einstein condensation, whose onset in a quantum liquid leads to phenomena such as superfluidity and superconductivity. A Bose-Einstein condensate is generally defined as a macroscopic occupation of a single-particle quantum state, a phenomenon technically referred to as off-diagonal long-range order due to non-vanishing off-diagonal components of the single-particle density matrix. The wavefunction of the condensate is an order parameter whose phase is essential in characterizing the coherence and superfluid phenomena. The long-range spatial coherence leads to the existence of phase-locked multiple condensates in an array of superfluid helium, superconducting Josephson junctions or atomic Bose-Einstein condensates. Under certain circumstances, a quantum phase difference of pi is predicted to develop among weakly coupled Josephson junctions. Such a meta-stable pi-state was discovered in a weak link of superfluid 3He, which is characterized by a 'p-wave' order parameter. The possible existence of such a pi-state in weakly coupled atomic Bose-Einstein condensates has also been proposed, but remains undiscovered. Here we report the observation of spontaneous build-up of in-phase ('zero-state') and antiphase ('pi-state') 'superfluid' states in a solid-state system; an array of exciton-polariton condensates connected by weak periodic potential barriers within a semiconductor microcavity. These in-phase and antiphase states reflect the band structure of the one-dimensional polariton array and the dynamic characteristics of metastable exciton-polariton condensates.     

An antidepressant that extends lifespan in adult Caenorhabditis elegans

The mechanisms that determine the lifespan of an organism are still largely a mystery. One goal of ageing research is to find drugs that would increase lifespan and vitality when given to an adult animal. To this end, we tested 88,000 chemicals for the ability to extend the lifespan of adult Caenorhabditis elegans nematodes. Here we report that a drug used as an antidepressant in humans increases C. elegans lifespan. In humans, this drug blocks neural signalling by the neurotransmitter serotonin. In C. elegans, the effect of the drug on lifespan is reduced or eradicated by mutations that affect serotonin synthesis, serotonin re-uptake at synapses, or either of two G-protein-coupled receptors: one that recognizes serotonin and the other that detects another neurotransmitter, octopamine. In vitro studies show that the drug acts as an antagonist at both receptors. Testing of the drug on dietary-restricted animals or animals with mutations that affect lifespan indicates that its effect on lifespan involves mechanisms associated with lifespan extension by dietary restriction. These studies indicate that lifespan can be extended by blocking certain types of neurotransmission implicated in food sensing in the adult animal, possibly leading to a state of perceived, although not real, starvation.     

A SNARE-adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles

Soluble NSF attachment protein receptors (SNAREs) are type II transmembrane proteins that have critical roles in providing the specificity and energy for transport-vesicle fusion and must therefore be correctly partitioned between vesicle and organelle membranes. Like all other cargo, SNAREs need to be sorted into the forming vesicles by direct interaction with components of the vesicles' coats. Here we characterize the molecular details governing the sorting of a SNARE into clathrin-coated vesicles, namely the direct recognition of the three-helical bundle H(abc) domain of the mouse SNARE Vti1b by the human clathrin adaptor epsinR (EPNR, also known as CLINT1). Structures of each domain and of their complex show that this interaction (dissociation constant 22 muM) is mediated by surface patches composed of approximately 15 residues each, the topographies of which are dependent on each domain's overall fold. Disruption of the interface with point mutations abolishes the interaction in vitro and causes Vti1b to become relocalized to late endosomes and lysosomes. This new class of highly specific, surface-surface interaction between the clathrin coat component and the cargo is distinct from the widely observed binding of short, linear cargo motifs by the assembly polypeptide (AP) complex and GGA adaptors and is therefore not vulnerable to competition from standard motif-containing cargoes for incorporation into clathrin-coated vesicles. We propose that conceptually similar but mechanistically different interactions will direct the post-Golgi trafficking of many SNAREs.     

Adaptive immunity maintains occult cancer in an equilibrium state

The capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes that function either independently or in sequence: elimination (cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium (expansion of transformed cells is held in check by immunity); and escape (tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected (occult) cancer from organ donor into immunosuppressed recipients. Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo. We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods.     

A synaptic memory trace for cortical receptive field plasticity

Receptive fields of sensory cortical neurons are plastic, changing in response to alterations of neural activity or sensory experience. In this way, cortical representations of the sensory environment can incorporate new information about the world, depending on the relevance or value of particular stimuli. Neuromodulation is required for cortical plasticity, but it is uncertain how subcortical neuromodulatory systems, such as the cholinergic nucleus basalis, interact with and refine cortical circuits. Here we determine the dynamics of synaptic receptive field plasticity in the adult primary auditory cortex (also known as AI) using in vivo whole-cell recording. Pairing sensory stimulation with nucleus basalis activation shifted the preferred stimuli of cortical neurons by inducing a rapid reduction of synaptic inhibition within seconds, which was followed by a large increase in excitation, both specific to the paired stimulus. Although nucleus basalis was stimulated only for a few minutes, reorganization of synaptic tuning curves progressed for hours thereafter: inhibition slowly increased in an activity-dependent manner to rebalance the persistent enhancement of excitation, leading to a retuned receptive field with new preference for the paired stimulus. This restricted period of disinhibition may be a fundamental mechanism for receptive field plasticity, and could serve as a memory trace for stimuli or episodes that have acquired new behavioural significance.     

Base-excision repair of oxidative DNA damage

Maintaining the chemical integrity of DNA in the face of assault by oxidizing agents is a constant challenge for living organisms. Base-excision repair has an important role in preventing mutations associated with a common product of oxidative damage to DNA, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high background of undamaged bases. The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer. The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.     

First-passage times in complex scale-invariant media

How long does it take a random walker to reach a given target point? This quantity, known as a first-passage time (FPT), has led to a growing number of theoretical investigations over the past decade. The importance of FPTs originates from the crucial role played by first encounter properties in various real situations, including transport in disordered media, neuron firing dynamics, spreading of diseases or target search processes. Most methods of determining FPT properties in confining domains have been limited to effectively one-dimensional geometries, or to higher spatial dimensions only in homogeneous media. Here we develop a general theory that allows accurate evaluation of the mean FPT in complex media. Our analytical approach provides a universal scaling dependence of the mean FPT on both the volume of the confining domain and the source-target distance. The analysis is applicable to a broad range of stochastic processes characterized by length-scale-invariant properties. Our theoretical predictions are confirmed by numerical simulations for several representative models of disordered media, fractals, anomalous diffusion and scale-free networks.