Expanding the proteome of an RNA virus by phosphorylation of an intrinsically disordered viral protein

The human proteome contains myriad intrinsically disordered proteins. Within intrinsically disordered proteins, polyproline-II motifs are often located near sites of phosphorylation. Wehave used an unconventional experimental paradigm to discover that phosphorylation by protein kinase A (PKA) occurs in the intrinsically disordered domain of hepatitis C virus nonstructural protein 5A (NS5A) on Thr-2332 near one of its polyproline-II motifs. Phosphorylation shifts the conformational ensemble of the NS5A intrinsically disordered domain to a state that permits detection of the polyproline motif by using 15N-, 13C-based multidimensional NMR spectroscopy. PKA-dependent proline resonances were lost in the presence of the Src homology 3 domain of c-Src, consistent with formation of a complex. Changing Thr-2332 to alanine in hepatitisCvirus genotype 1b reduced the steady-state level of RNA by 10-fold; this change was lethal for genotype 2a. The lethal phenotype could be rescued by changing Thr-2332 to glutamic acid, a phosphomimetic substitution. Immunofluorescence and transmission electron microscopy showed that the inability to produce Thr(P)-2332-NS5A caused loss of integrity of the virus-induced membranous web/replication organelle. An even more extreme phenotype was observed in the presence of small molecule inhibitors of PKA. We conclude that the PKA-phosphorylated form of NS5A exhibits unique structure and function relative to the unphosphorylated protein. We suggest that post-translational modification of viral proteins containing intrinsic disorder may be a general mechanism to expand the viral proteome without a corresponding expansion of the genome

The geology and geophysics of Kuiper Belt object (486958) Arrokoth

The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, are primitive objects preserving information about Solar System formation. The New Horizons spacecraft flew past one of these objects, the 36 km long contact binary (486958) Arrokoth (2014 MU69), in January 2019. Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters diameter) within a radius of 8000 km, and has a lightly-cratered smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism

Cotton in the new millennium: advances, economics, perceptions and problems

Cotton is the most significant natural fibre and has been a preferred choice of the textile industry and consumers since the industrial revolution began. The share of man-made fibres, both regenerated and synthetic fibres, has grown considerably in recent times but cotton production has also been on the rise and accounts for about half of the fibres used for apparel and textile goods. To cotton’s advantage, the premium attached to the presence of cotton fibre and the general positive consumer perception is well established, however, compared to commodity man-made fibres and high performance fibres, cotton has limitations in terms of its mechanical properties but can help to overcome moisture management issues that arise with performance apparel during active wear. This issue of Textile Progress aims to: i. Report on advances in cotton cultivation and processing as well as improvements to conventional cotton cultivation and ginning. The processing of cotton in the textile industry from fibre to finished fabric, cotton and its blends, and their applications in technical textiles are also covered. ii. Explore the economic impact of cotton in different parts of the world including an overview of global cotton trade. iii. Examine the environmental perception of cotton fibre and efforts in organic and genetically-modified (GM) cotton production. The topic of naturally-coloured cotton, post-consumer waste is covered and the environmental impacts of cotton cultivation and processing are discussed. Hazardous effects of cultivation, such as the extensive use of pesticides, insecticides and irrigation with fresh water, and consequences of the use of GM cotton and cotton fibres in general on the climate are summarised and the effects of cotton processing on workers are addressed. The potential hazards during cotton cultivation, processing and use are also included. iv. Examine how the properties of cotton textiles can be enhanced, for example, by improving wrinkle recovery and reducing the flammability of cotton fibre

Melting of 2D nonequilibrium structures at low and high constraints

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Women in hospital medicine in the United Kingdom: glass ceiling, preference, prejudice or cohort effect?

OBJECTIVE—To assess from official statistics whether there is evidence that the careers of women doctors in hospitals do not progress in the same way as those of men.
DESIGN—The proportions of female hospital doctors overall (1963-96), and in the specialties of medicine, surgery, obstetrics and gynaecology, pathology, radiology/radiotherapy, anaesthetics and psychiatry (1974-1996) were examined. Additionally data were examined on career preferences and intentions from pre-registration house officers, final year medical students, and medical school applicants (1966-1991).
ANALYSIS—Data were analysed according to cohort of entry to medical school to assess the extent of disproportionate promotion.
RESULTS—The proportion of women in hospital career posts was largely explained by the rapidly increasing proportion of women entering medical school during the past three decades. In general there was little evidence for disproportionate promotion of women in hospital careers, although in surgery, hospital medicine and obstetrics and gynaecology, fewer women seemed to progress beyond the SHO grade, and in anaesthetics there were deficits of women at each career stage. Analyses of career preferences and intentions suggest that disproportionate promotion cannot readily be explained as differential choice by women.
CONCLUSIONS—Although there is no evidence as such of a "glass ceiling" for women doctors in hospital careers, and the current paucity of women consultants primarily reflects historical trends in the numbers of women entering medical school, there is evidence in some cases of disproportionate promotion that is best interpreted as direct or indirect discrimination.