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Substance P is a neuropeptide that evokes slow excitation after activation of its cognate G-protein-coupled receptor. This study investigates the downstream pathway and shows that it depends on Src family kinases, rather than G-protein signalling.
It is shown that the cell surface protein prominin 1 (also known as CD133) marks stem cells in the mouse intestine. Using lineage-tracing experiments, it is shown that intestinal tumours can originate in these cells when the Wnt signalling pathway is aberrantly activated.
The DNA and RNA polymerases encode proofreading activities that help to ensure the fidelity of the readout. The ribosome, which synthesizes protein, was believed to lack a similar activity that would recognize errors after a peptide bond had been formed. This study provides evidence that the ribosome does have such a quality control mechanism. It is shown that after an incorrect amino acid has been incorporated into the growing polypeptide chain, there is a general loss of specificity in the ribosome's active site, leading to an accumulation of errors that triggers premature termination of peptide synthesis.
This study tests the importance of the intrinsic DNA sequence preferences of nucleosomes by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map is similar to in vivo nucleosome maps, indicating that the organization of nucleosomes in vivo is largely governed by the underlying genomic DNA sequence.
An early cellular response to the occurrence of DNA double-strand breaks in mammals is the phosphorylation of the specialized histone variant H2A.X at Ser 139. The chromatin remodelling factor WSTF is found to phosphorylate H2A.X at another site, Tyr 142. Tyrosine phosphorylation has not been observed previously on histones.
It is shown that type of repair pathway, known as postreplication repair, permits cells to replicate their DNA when it is damaged, thereby avoiding the activation of a cellular response that would inhibit proliferation.
In sleeping adult zebra finches, forebrain premotor neuron activity is proposed to reflect daytime singing episodes. This study shows that in juvenile songbirds yet to master their song, auditory exposure to an adult 'tutor' song produced profound changes in the premotor neuronal activity during the subsequent sleep session. These changes in night time activity preceded and reflected tutor-song induced changes in singing the next day.
It is shown that after activation, Ire1 molecules cluster into discrete foci containing high order oligomers on the endoplasmic reticulum membrane. HAC1 mRNA is recruited to these foci by means of a sequence in its 3′ UTR and is processes at these sites. Disruption of either Ire1 clustering or HAC1 mRNA recruitment impairs UPR signalling. Hence HAC1 mRNA is delivered to a site where it is processed thus ensuring that it is only translated when UPR is on.
Accumulation of misfolded proteins results in the activation of the unfolded protein response (UPR) in the endoplasmic reticulum. Ire1 is important in this pathway and functions as a kinase and endoribonuclease. This paper solves the crystal structure of Ire1 kinase and shows that it undergoes spontaneous assembly into a rod-shaped oligomer. This arrangement positions the kinase domains for trans-autophosphorylation, orders the RNase domains and creates an interaction site for mRNA substrate binding.
Dietary restriction can extend lifespan in various species. In mammals, intermittent fasting can also extend lifespan and reduce the incidence of age-related disorders. It is shown that intermittent fasting can effectively extend the lifespan of Caenorhabditis elegans, and that the low molecular weight GTPase RHEB-1 has a central role in lifespan regulation.
Indications of the presence of water in the atmosphere of the planet HD 189733b have recently been found in transmission spectra. This paper reports the detection of strong water absorption in a high signal-to-noise, mid-infrared emission spectrum of the planet itself. The differences between these and previous observations are significant and admit the possibility that predicted planetary-scale dynamical weather structures might alter the emission spectrum over time.
Continental rifts initiate and develop through repeated episodes of faulting and magmatism, yet strain partitioning between faulting and magmatism during discrete rifting episodes remains poorly documented. It is shown that most of the strain during the July–August 2007 seismic crisis in the Natron rift, Tanzania, was released aseismically. This event provides evidence for strain accommodation by magma intrusion, in addition to slip along normal faults, during the initial stages of continental rifting, and before significant crustal thinning.
A new method to convert secondary alcohols in their single mirror image form into tertiary alcohols has been developed. Starting from a single enantiomer of the secondary alcohol, either mirror image form of the tertiary alcohol can be made with very high levels of stereocontrol. A broad range of tertiary alcohols can now be easily made by this method with very high levels of selectivity.
There is support for the idea that there are liquid oceans on several moons of the outer planets, with Jupiter's moon Europa having received the most attention. But it is unclear how these oceans remain liquid. This paper describes strong tidal dissipation (and heating) in the liquid oceans of such moons, and shows that a previously unconsidered tidal force due to obliquity has the right form and frequency to resonantly excite large-amplitude Rossby waves.
To realize scalable quantum information networks, it will be important to develop techniques for storage and retrieval of light at the single photon level. Quantum interfaces between light and matter have been demonstrated, but mainly with atomic gases that involve sophisticated schemes to trap the atoms. This paper demonstrates a potentially more practical approach; coherent and reversible mapping of a light field with less than one photon per pulse onto an ensemble of ∼107 atoms naturally trapped in a solid state medium. The state of the light is mapped onto collective atomic excitations on an optical transition and stored for a pre-programmed time up of to one microsecond before being retrieved again.
Brain development requires the coordinated differentiation and wiring of numerous neuronal cell types based on a relatively limited set of genes. This study dissects the interplay of positive and negative gene transcription regulators, which orchestrate the coordinated synthesis of specific photosensitive pigments and axon guidance molecules in a subset of Drosophila photoreceptor neurons.
Antigenic variation is a process by which pathogens switch surface antigen expression during infection to escape immune recognition. Giardia lamblia, a major cause of parasitic diarrhoea, is now shown to regulate antigenic variation by RNA interference.
In the Saccharomyces cerevisiae pheromone response pathway, the MAP kinase Fus3 mediates the rapid negative feedback that adjusts the dose–response of the downstream system response to match that of receptor-ligand binding. This 'dose–response alignment' improves the fidelity of information transmission. Negative feedback could be used as a general mechanism in signalling systems to align dose–responses.