The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress

Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the cytoplasm. First, the capsid buds through the inner nuclear membrane, becoming coated with nuclear egress complex (NEC) protein. This yields a primary enveloped virion (PEV) whose envelope fuses with the outer nuclear membrane, releasing the capsid into the cytoplasm. We investigated the associated molecular mechanisms by isolating PEVs from US3-null-infected cells and imaging them by cryo-electron microscopy and tomography. (pUS3 is a viral protein kinase in whose absence PEVs accumulate in the perinuclear space.) Unlike mature extracellular virions, PEVs have very few lycoprotein spikes. PEVs are ~20% smaller than mature virions, and the little space available between the capsid and the NEC layer suggests that most tegument proteins are acquired later in the egress pathway. Previous studies have proposed that NEC is organized as hexamers in honeycomb arrays in PEVs, but we find arrays of heptameric rings in extracts from US3-nullinfected cells. In a PEV, NEC contacts the capsid predominantly via the pUL17/pUL25 complexes which are located close to the capsid vertices. Finally, the NEC layer dissociates from the capsid as it leaves the nucleus, possibly in response to pUS3- mediated phosphorylation. Overall, nuclear egress emerges as a process driven by a program of multiple weak interactions

Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid

The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250-Å diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major changes in structure and composition as it matures, a process driven by proteolysis and expulsion of the internal scaffolding protein. Assembly also relies on an external scaffolding protein, the triplex, an α2β heterotrimer that coordinates neighboring capsomers in the procapsid and becomes a stabilizing clamp in the mature capsid. To investigate the mechanisms that regulate its assembly, we developed a novel isolation procedure for the metastable procapsid and collected a large set of cryo-electron microscopy data. In addition to procapsids, these preparations contain maturation intermediates, which were distinguished by classifying the images and calculating a three-dimensional reconstruction for each class. Appraisal of the procapsid structure led to a new model for assembly; in it, the protomer (assembly unit) consists of one triplex, surrounded by three major capsid protein (MCP) subunits. The model exploits the triplexes’ departure from 3-fold symmetry to explain the highly skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16 architecture. These observations also yielded new insights into maturation

Radioactive 26Al and massive stars in the Galaxy

Gamma-rays from radioactive 26Al (half life ~7.2 10^5 yr) provide a 'snapshot' view of ongoing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along the plane of the Galaxy. This led to the conclusion1 that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show locally-produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/-0.8) M_sol of 26Al. We use this to estimate that the frequency of core collapse (i.e. type Ib/c and type II) supernovae to be 1.9(+/- 1.1) events per century.Comment: accepted for publication in Nature, 24 pages including Online Supplements, 11 figures, 1 tabl

Some methods for blindfolded record linkage

BACKGROUND: The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. METHODS: A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. RESULTS: The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. CONCLUSION: Although the protocols described in this paper are not unconditionally secure, they do suggest the feasibility, with the aid of modern cryptographic techniques and high speed communication networks, of a general purpose probabilistic record linkage system which permits record linkage studies to be carried out with negligible risk of invasion of personal privacy

Juvenile obesity and its association with utilisation and costs of pharmaceuticals - results from the KiGGS study

<p>Abstract</p> <p>Background</p> <p>According to a national reference, 15% of German children and adolescents are overweight (including obese) and 6.3% are obese. An earlier study analysed the impact of childhood overweight and obesity on different components of direct medical costs (physician, hospital and therapists). To complement the existing literature for Germany, this study aims to explore the association of body mass index (BMI) with utilisation of pharmaceuticals and related costs in German children and adolescents.</p> <p>Methods</p> <p>Based on data from 14, 836 respondents aged 3-17 years in the German Interview and Examination Survey for Children and Adolescents (KiGGS), drug intake and associated costs were estimated using a bottom-up approach. To investigate the association of BMI with utilisation and costs, univariate analyses and multivariate generalised mixed models were conducted.</p> <p>Results</p> <p>There was no significant difference between BMI groups regarding the probability of drug utilisation. However, the number of pharmaceuticals used was significantly higher (14%) for obese children than for normal weight children. Furthermore, there was a trend for more physician-prescribed medication in obese children and adolescents. Among children with pharmaceutical intake, estimated costs were 24% higher for obese children compared with the normal weight group.</p> <p>Conclusions</p> <p>This is the first study to estimate excess drug costs for obesity based on a representative cross-sectional sample of the child and adolescent population in Germany. The results suggest that obese children should be classified as a priority group for prevention. This study complements the existing literature and provides important information concerning the relevance of childhood obesity as a health problem.</p

The effectiveness of the Austrian disease management programme for type 2 diabetes: a cluster-randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Disease management programmes (DMPs) are costly and impose additional work load on general practitioners (GPs). Data on their effectiveness are inconclusive. We therefore conducted a cluster-randomised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care.</p> <p>Methods</p> <p>All GPs of Salzburg-province were invited to participate. After cluster-randomisation by district, all patients with diabetes type 2 were recruited consecutively from 7-11/2007. The DMP, consisting mainly of physician and patient education, standardised documentation and agreement on therapeutic goals, was implemented in the intervention group while the control group received usual care. We aimed to show superiority of the intervention regarding metabolic control and process quality. The primary outcome measure was a change in HbA1c after one year. Secondary outcomes were days in the hospital, blood pressure, lipids, body mass index (BMI), enrolment in patient education and regular guideline-adherent examination. Blinding was not possible.</p> <p>Results</p> <p>92 physicians recruited 1489 patients (649 intervention, 840 control). After 401 ± 47 days, 590 intervention-patients and 754 controls had complete data. In the intention to treat analysis (ITT) of all 1489 patients, HbA1c decreased 0.41% in the intervention group and 0.28% in controls. The difference of -0.13% (95% CI -0.24; -0.02) was significant at p = 0.026. Significance was lost in mixed models adjusted for baseline value and cluster-effects (adjusted mean difference -0.03 (95% CI -0.15; 0.09, p = 0.607). Of the secondary outcome measures, BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments (-0.53 kg/m²; 95% CI -1.03;-0.02; p = 0.014 and -0.10 mmol/l; 95% CI -0.21; -0.003; p = 0.043). Additionally, more patients received patient education (49.5% vs. 20.1%, p < 0.0001), eye- (71.0% vs. 51.2%, p < 0.0001), foot examinations (73.8% vs. 45.1%, p < 0.0001), and regular HbA1c checks (44.1% vs. 36.0%, p < 0.01) in the intervention group.</p> <p>Conclusion</p> <p>The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction, but does not significantly improve metabolic control for patients with type 2 diabetes mellitus. Whether the small benefit seen in secondary outcome measures leads to better patient outcomes, remains unclear.</p> <p>Trial Registration</p> <p>Current Controlled trials Ltd., ISRCTN27414162.</p

Evaluating the effects of catch-and-release angling on Cape stumpnose Rhabdosargus holubi in a South African estuary

Fisheries managers are increasingly promoting catch and release (C&R) as a means to manage recreational fish stocks. Several commonly used output regulations, including bag and size limits, require the mandatory release of captured fishes by anglers. In addition to mandatory C&R, conservation-conscious anglers have adopted voluntary C&R behaviour as a result of the noticeable declines in the populations of many fishery species and this behaviour is becoming increasingly popular among recreational anglers (Cooke et al. 2013a). The combination of mandatory and voluntary C&R behaviour is substantial, as Raby et al. (2014) estimated that 60% of fish captured in global recreational fisheries are released. In South Africa, Cowley et al. (2013) found that a large proportion (mean 74% [SD 7.3]) of the five most-dominant fishery species captured in the Sundays Estuary recreational fishery were released

Tests of multiple molecular markers for the identification of Great Spotted and Syrian Woodpeckers and their hybrids

Great Spotted and Syrian Woodpeckers (Dendrocopos major and D. syriacus) are known to hybridize in nature; however, the extent of this phenomenon is not known due to difficulties in hybrid detection based on plumage analyses. Here, we tested five markers (one mitochondrial and four nuclear) and a set of six microsatellite loci for the identification of these two Woodpeckers and their hybrids. Sequencing of DNA from 26 individuals of both Woodpeckers from different parts of their ranges: one allopatric (D. major; Norway) and two sympatric (Poland and Bulgaria) showed that both species can be clearly separated based on all sequence markers. The highest number of fixed nucleotide sites were found in the mtDNA control region and intron 5 of the transforming growth factor. Analyses of microsatellite data distinguished the two species, but all loci showed a large number of common alleles and their utility in identifying hybrids is therefore doubtful. According to the DNA sequence analyses, 2 out of 18 specimens within the sympatric range in Poland were identified as possible hybrids, most probably paternal backcrosses. Moreover, both hybrids are from synantropic populations (settled in cities), whereas none of the D. major sampled in forests and in its allopatric range (Norway) showed signs of an intermixed genotype. Further research on hybridization and introgression in woodpeckers is undoubtedly needed and could be useful for understanding ecological and ethological interactions among these species, particularly for D. syriacus, which is relatively rare in Europe

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.