New images from NASA’s Lunar Reconnaissance Orbiter (LRO) spacecraft show the moon’s crust is being stretched, forming minute valleys in a few small areas on the lunar surface. Scientists propose…
For more details, go to The Hindu - Sci-Tech
The deepest-dwelling land animal in the world has been found almost 2 kilometres underground
For more details, go to New Scientist - Online News
Mice bred to have increased levels of sirtuin 6 – an enzyme found in humans – lived 15 per cent longer lives
For more details, go to New Scientist - Online News
The human male Y chromosome will not mutate itself out of existence just 4.6 million years from now – confounding expectations
For more details, go to New Scientist - Online News
All today’s stories on newscientist.com, including: Europe will vote to keep Canadian tar sands out and rolling stones could mean Mars still rocks
For more details, go to New Scientist - Online News
Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1–M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the Gq/11-coupled M3 mAChR (‘M3 receptor’, from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the Gi/o-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.
For more details, go to Nature Latest Research
Since its discovery in the early 1990s the deleted in colorectal cancer (DCC) gene, located on chromosome 18q21, has been proposed as a tumour suppressor gene as its loss is implicated in the majority of advanced colorectal and many other cancers. DCC belongs to the family of netrin 1 receptors, which function as dependence receptors as they control survival or apoptosis depending on ligand binding. However, the role of DCC as a tumour suppressor remains controversial because of the rarity of DCC-specific mutations and the presence of other tumour suppressor genes in the same chromosomal region. Here we show that in a mouse model of mammary carcinoma based on somatic inactivation of p53, additional loss of DCC promotes metastasis formation without affecting the primary tumour phenotype. Furthermore, we demonstrate that in cell cultures derived from p53-deficient mouse mammary tumours DCC expression controls netrin-1-dependent cell survival, providing a mechanistic basis for the enhanced metastatic capacity of tumour cells lacking DCC. Consistent with this idea, in vivo tumour-cell survival is enhanced by DCC loss. Together, our data support the function of DCC as a context-dependent tumour suppressor that limits survival of disseminated tumour cells.
For more details, go to Nature Latest Research
Arising from F. He & S. P. Hubbell Nature 473, 368–371 ()(2011).
Statistical relationships between habitat area and the number of species observed (species–area relationships, SARs) are sometimes used to assess extinction risks following habitat destruction or loss of climatic suitability. He and Hubbell argue that the numbers of species confined to—rather than observed in—different areas (endemics–area relationships, EARs) should be used instead of SARs, and that SAR-based extinction estimates in the literature are too high. We suggest that He and Hubbell’s SAR estimates are biased, that the empirical data they use are not appropriate to calculate extinction risks, and that their statements about extinction risks from climate change do not take into account non-SAR-based estimates or recent observations. Species have already responded to climate change in a manner consistent with high future extinction risks.
For more details, go to Nature Latest Research
Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60–80 nm in diameter, yet some must increase their size to accommodate 300–400 nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, cranio-lenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive. Here, we identified the ubiquitin ligase CUL3–KLHL12 as a regulator of COPII coat formation. CUL3–KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats. As a result, ubiquitylation by CUL3–KLHL12 is essential for collagen export, yet less important for the transport of small cargo. We conclude that monoubiquitylation controls the size and function of a vesicle coat.
For more details, go to Nature Latest Research
Arising from F. He & S. P. Hubbell Nature 473, 368–371 (2011).
He and Hubbell developed a sampling theory for the species–area relationship (SAR) and the endemics–area relationship (EAR). They argued that the number of extinctions after habitat loss is described by the EAR and that extinction rates in previous studies are overestimates because the EAR is always lower than the SAR. Here we show that their conclusion is not general and depends on the geometry of habitat destruction and the scale of the SAR. We also question their critique of the Millennium Ecosystem Assessment estimates, as those estimates are not dependent on the SAR only, although important uncertainties remain due to other methodological issues.
For more details, go to Nature Latest Research
Career News