A dynamic upper atmosphere of Venus as revealed by VIRTIS on Venus Express

The upper atmosphere of a planet is a transition region in which energy is transferred between the deeper atmosphere and outer space. Molecular emissions from the upper atmosphere (90-120 km altitude) of Venus can be used to investigate the energetics and to trace the circulation of this hitherto little-studied region. Previous spacecraft and ground-based observations of infrared emission from CO2, O2 and NO have established that photochemical and dynamic activity controls the structure of the upper atmosphere of Venus. These data, however, have left unresolved the precise altitude of the emission owing to a lack of data and of an adequate observing geometry. Here we report measurements of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm, extending from 90 to 120 km altitude, and of night-side O2 emission extending from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and varies with solar zenith angle over a range of approximately 10 km. This confirms previous modelling, and permits the beginning of a systematic study of the variability of the emission. The O2 peak emission happens at 96 km +/- 1 km, which is consistent with three-body recombination of oxygen atoms transported from the day side by a global thermospheric sub-solar to anti-solar circulation, as previously predicted.     

The beet R locus encodes a new cytochrome P450 required for red betalain production

Anthocyanins are red and violet pigments that color flowers, fruits and epidermal tissues in virtually all flowering plants. A single order, Caryophyllales, contains families in which an unrelated family of pigments, the betalains, color tissues normally pigmented by anthocyanins. Here we show that CYP76AD1 encoding a novel cytochrome P450 is required to produce the red betacyanin pigments in beets. Gene silencing of CYP76AD1 results in loss of red pigment and production of only yellow betaxanthin pigment. Yellow betalain mutants are complemented by transgenic expression of CYP76AD1, and an insertion in CYP76AD1 maps to the R locus that is responsible for yellow versus red pigmentation. Finally, expression of CYP76AD1 in yeast verifies its position in the betalain biosynthetic pathway. Thus, this cytochrome P450 performs the biosynthetic step that provides the cyclo-DOPA moiety of all red betacyanins. This discovery will contribute to our ability to engineer this simple, nutritionally valuable pathway into heterologous species.     

A luminous quasar at a redshift of z = 7.085

The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULAS?J112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULAS?J1120+0641 has a luminosity of 6.3 × 10(13)L(⊙) and hosts a black hole with a mass of 2 × 10(9)M(⊙) (where L(⊙) and M(⊙) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULAS?J1120+0641 is 1.9?megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Lyα damping wing, suggesting that the neutral fraction of the intergalactic medium in front of ULAS?J1120+0641 exceeded 0.1.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.     

HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites

The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity. This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization, we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization.     

A common polymorphism acts as an intragenic modifier of mutant p53 behaviour

The p73 protein, a homologue of the tumour-suppressor protein p53, can activate p53-responsive promoters and induce apoptosis in p53-deficient cells. Here we report that some tumour-derived p53 mutants can bind to and inactivate p73. The binding of such mutants is influenced by whether TP53 (encoding p53) codon 72, by virtue of a common polymorphism in the human population, encodes Arg or Pro. The ability of mutant p53 to bind p73, neutralize p73-induced apoptosis and transform cells in cooperation with EJ-Ras was enhanced when codon 72 encoded Arg. We found that the Arg-containing allele was preferentially mutated and retained in squamous cell tumours arising in Arg/Pro germline heterozygotes. Thus, inactivation of p53 family members may contribute to the biological properties of a subset of p53 mutants, and a polymorphic residue within p53 affects mutant behaviour.     

Effect of salinity on seed germination of Triglochin maritima under various temperature regimes

Triglochin maritima L. (arrow grass), an herbaceous perennial in the family Juncaginacea, is widely distributed in inland and coastal salt marshes of North America. Triglochin maritima seeds from a population growing in a salt marsh at Faust, Utah, were germinated at 4 temperature regimes (12-h night/12-h day, 5-15° C, 10-20° C, and 15-25° C) and 5 salinities (0, 100, 200, 300, 400, and 500 mol m -3 NaCl) to determine optimal conditions for germination and level of salt tolerance. Ungerminated seeds were returned to distilled water after 20 d to determine whether seeds could recover from salinity treatments. Maximum germination occurred in distilled water, and increases in NaCl concentration progressively inhibited seed germination. No seeds germinated at concentrations higher than 400 mol m -3 NaCl. A temperature regime of low night (5° C) and high day (25° C) temperature yielded maximum germination; all other temperature regimes significantly inhibited seed germination relative to this optimum. Recovery of germination was highest at 5-25° C and lowest at 5-15° C. Recovery of seed germination when seeds were transferred to distilled water from salt solutions was highest at 5-25° C (72%) for seeds exposed to the 500 mol m -3 NaCl pretreatment and significantly reduced at other temperature regimes. The recovery germination response indicates a synergistic inhibitory interaction effect on germination when seeds were exposed to high salinities at suboptimal thermoperiods.     

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approximately 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.     

Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema

We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.