Basic amino-acid side chains regulate transmembrane integrin signalling

Side chains of Lys/Arg near transmembrane domain (TMD) membrane-water interfaces can 'snorkel', placing their positive charge near negatively charged phospholipid head groups; however, snorkelling's functional effects are obscure. Integrin β TMDs have such conserved basic amino acids. Here we use NMR spectroscopy to show that integrin β(3)(Lys?716) helps determine β(3) TMD topography. The α(ΙΙb)β(3) TMD structure indicates that precise β(3) TMD crossing angles enable the assembly of outer and inner membrane 'clasps' that hold the αβ TMD together to limit transmembrane signalling. Mutation of β(3)(Lys?716) caused dissociation of α(ΙΙb)β(3) TMDs and integrin activation. To confirm that altered topography of β(3)(Lys?716) mutants activated α(ΙΙb)β(3), we used directed evolution of β(3)(K716A) to identify substitutions restoring default state. Introduction of Pro(711) at the midpoint of β(3) TMD (A711P) increased α(ΙΙb)β(3) TMD association and inactivated integrin α(ΙΙb)β(3)(A711P,K716A). β(3)(Pro?711) introduced a TMD kink of 30?±?1° precisely at the border of the outer and inner membrane clasps, thereby decoupling the tilt between these segments. Thus, widely occurring snorkelling residues in TMDs can help maintain TMD topography and membrane-embedding, thereby regulating transmembrane signalling.     

Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway

Plants must coordinate the regulation of biochemistry and anatomy to optimize photosynthesis and water-use efficiency. The formation of stomata, epidermal pores that facilitate gas exchange, is highly coordinated with other aspects of photosynthetic development. The signalling pathways controlling stomata development are not fully understood, although mitogen-activated protein kinase (MAPK) signalling is known to have key roles. Here we demonstrate in Arabidopsis that brassinosteroid regulates stomatal development by activating the MAPK kinase kinase (MAPKKK) YDA (also known as YODA). Genetic analyses indicate that receptor kinase-mediated brassinosteroid signalling inhibits stomatal development through the glycogen synthase kinase 3 (GSK3)-like kinase BIN2, and BIN2 acts upstream of YDA but downstream of the ERECTA family of receptor kinases. Complementary in vitro and in vivo assays show that BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4, and that activities of downstream MAPKs are reduced in brassinosteroid-deficient mutants but increased by treatment with either brassinosteroid or GSK3-kinase inhibitor. Our results indicate that brassinosteroid inhibits stomatal development by alleviating GSK3-mediated inhibition of this MAPK module, providing two key links; that of a plant MAPKKK to its upstream regulators and of brassinosteroid to a specific developmental output.     

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.     

IKKalpha controls formation of the epidermis independently of NF-kappaB

The IKKalpha and IKKbeta catalytic subunits of IkappaB kinase (IKK) share 51% amino-acid identity and similar biochemical activities: they both phosphorylate IkappaB proteins at serines that trigger their degradation. IKKalpha and IKKbeta differ, however, in their physiological functions. IKKbeta and the IKKgamma/NEMO regulatory subunit are required for activating NF-kappaB by pro-inflammatory stimuli and preventing apoptosis induced by tumour necrosis factor-alpha (refs 5,6,7,8,9,10,11). IKKalpha is dispensable for these functions, but is essential for developing the epidermis and its derivatives. The mammalian epidermis is composed of the basal, spinous, granular and cornified layers. Only basal keratinocytes can proliferate and give rise to differentiated derivatives, which on full maturation undergo enucleation to generate the cornified layer. Curiously, keratinocyte-specific inhibition of NF-kappaB, as in Ikkalpha-/- mice, results in epidermal thickening but does not block terminal differentiation. It has been proposed that the epidermal defect in Ikkalpha-/- mice may be due to the failed activation of NF-kappaB. Here we show that the unique function of IKKalpha in control of keratinocyte differentiation is not exerted through its IkappaB kinase activity or through NF-kappaB. Instead, IKKalpha controls production of a soluble factor that induces keratinocyte differentiation.     

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.     

Spreading-rate dependence of melt extraction at mid-ocean ridges from mantle seismic refraction data

A variety of observations indicate that mid-ocean ridges produce less crust at spreading rates below 20 mm yr(-1) (refs 1-3), reflecting changes in fundamental ridge processes with decreasing spreading rate. The nature of these changes, however, remains uncertain, with end-member explanations being decreasing shallow melting or incomplete melt extraction, each due to the influence of a thicker thermal lid. Here we present results of a seismic refraction experiment designed to study mid-ocean ridge processes by imaging residual mantle structure. Our results reveal an abrupt lateral change in bulk mantle seismic properties associated with a change from slow to ultraslow palaeo-spreading rate. Changes in mantle velocity gradient, basement topography and crustal thickness all correlate with this spreading-rate change. These observations can be explained by variations in melt extraction at the ridge, with a gabbroic phase preferentially retained in the mantle at slower spreading rates. The estimated volume of retained melt balances the approximately 1.5-km difference in crustal thickness, suggesting that changes in spreading rate affect melt-extraction processes rather than total melting.     

Sequencing of a rice centromere uncovers active genes

Centromeres are the last frontiers of complex eukaryotic genomes, consisting of highly repetitive sequences that resist mapping, cloning and sequencing. The centromere of rice Chromosome 8 (Cen8) has an unusually low abundance of highly repetitive satellite DNA, which allowed us to determine its sequence. A region of approximately 750 kb in Cen8 binds rice CENH3, the centromere-specific H3 histone. CENH3 binding is contained within a larger region that has abundant dimethylation of histone H3 at Lys9 (H3-Lys9), consistent with Cen8 being embedded in heterochromatin. Fourteen predicted and at least four active genes are interspersed in Cen8, along with CENH3 binding sites. The retrotransposons located in and outside of the CENH3 binding domain have similar ages and structural dynamics. These results suggest that Cen8 may represent an intermediate stage in the evolution of centromeres from genic regions, as in human neocentromeres, to fully mature centromeres that accumulate megabases of homogeneous satellite arrays.     

Probable observation of a supersolid helium phase

When liquid (4)He is cooled below 2.176 K, it undergoes a phase transition-Bose-Einstein condensation-and becomes a superfluid with zero viscosity. Once in such a state, it can flow without dissipation even through pores of atomic dimensions. Although it is intuitive to associate superflow only with the liquid phase, it has been proposed theoretically that superflow can also occur in the solid phase of (4)He. Owing to quantum mechanical fluctuations, delocalized vacancies and defects are expected to be present in crystalline solid (4)He, even in the limit of zero temperature. These zero-point vacancies can in principle allow the appearance of superfluidity in the solid. However, in spite of many attempts, such a 'supersolid' phase has yet to be observed in bulk solid (4)He. Here we report torsional oscillator measurements on solid helium confined in a porous medium, a configuration that is likely to be more heavily populated with vacancies than bulk helium. We find an abrupt drop in the rotational inertia of the confined solid below a certain critical temperature. The most likely interpretation of the inertia drop is entry into the supersolid phase. If confirmed, our results show that all three states of matter-gas, liquid and solid-can undergo Bose-Einstein condensation.