The level and duration of RSV-specific maternal IgG in infants in Kilifi Kenya

Background Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants. The rate of decay of RSV-specific maternal antibodies (RSV-matAb), the factors affecting cord blood levels, and the relationship between these levels and protection from infection are poorly defined. Methods A birth cohort (n = 635) in rural Kenya, was studied intensively to monitor infections and describe age-related serological characteristics. RSV specific IgG antibody (Ab) in serum was measured by the enzyme linked immunosorbent assay (ELISA) in cord blood, consecutive samples taken 3 monthly, and in paired acute and convalescent samples. A linear regression model was used to calculate the rate of RSV-matAb decline. The effect of risk factors on cord blood titres was investigated. Results The half-life of matAb in the Kenyan cohort was calculated to be 79 days (95% confidence limits (CL): 76–81 days). Ninety seven percent of infants were born with RSV-matAb. Infants who subsequently experienced an infection in early life had significantly lower cord titres of anti-RSV Ab in comparison to infants who did not have any incident infection in the first 6 months (P = 0.011). RSV infections were shown to have no effect on the rate of decay of RSV-matAb. Conclusion Maternal-specific RSV Ab decline rapidly following birth. However, we provide evidence of protection against severe disease by RSV-matAb during the first 6–7 months. This suggests that boosting maternal-specific Ab by RSV vaccination may be a useful strategy to consider

Influenza virus protecting RNA : an effective prophylactic and therapeutic antiviral

Another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza RNA that has the potential to protect against any influenza A virus in any animal host. This protecting RNA (244 RNA) is incorporated into virions which although non-infectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A small intranasal dose of this 244 protecting virus (120 ng) completely protected mice against a simultaneous lethal (10 LD50) challenge with influenza A/WSN (H1N1) virus. 244 virus also protected mice against a strong challenge dose of all other subtypes tested (H2N2, H3N2, H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. 244 virus was 10 to 100-fold more active than previously characterised influenza A defective viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was clear therapeutic benefit when protecting 244 virus was administered 24-48 h after lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral which has the potential to combat influenza infections in humans, particularly when the infecting strain is not known, or is resistant to antiviral drugs

Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes

Acknowledgements The Rowett Institute of Nutrition and Health (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). POS is a PhD student supported by the Scottish Government (RESAS) and the Science Foundation Ireland, through a centre award to the APC Microbiome Institute, Cork, Ireland. Data Summary The high-quality draft genomes generated in this work were deposited at the European Nucleotide Archive under the following accession numbers: 1. Eubacterium rectale T1-815; CVRQ01000001–CVRQ0100 0090: http://www.ebi.ac.uk/ena/data/view/PRJEB9320 2. Roseburia faecis M72/1; CVRR01000001–CVRR010001 01: http://www.ebi.ac.uk/ena/data/view/PRJEB9321 3. Roseburia inulinivorans L1-83; CVRS01000001–CVRS0 100 0151: http://www.ebi.ac.uk/ena/data/view/PRJEB9322Peer reviewedPublisher PD

Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established

Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes

On Writ of Certiorari to the United States Court of Appeals for the Ninth Circuit, Brief of Product Liability Advisory Council, Inc., National Association of Manufacturers, Business Roundtable, and Chemical Manufacturers Association as Amici Curiae in Support of Respondent, William Daubert and Joyce Daubert, Individually and as Guardians Ad Litem for Jason Daubert, and Anita De Young, Individually and as Gaurdian Ad Litem for Eric Schuller v. Merrell Dow Pharmaceuticals, Inc.

The Federal Rules of Evidence exclude expert scientific testimony when it has been developed without regard for accepted scientific methods. This case focuses on expert scientific evidence. Such evidence plays a vital and often dispositive role in modern litigation. For scientific evidence to be helpful to the factfinder it must meet some minimal threshold of reliability. To hold otherwise would be to allow a system of adjudication based more on chance than on reason

The Kinetic Sunyaev-Zel'dovich Effect from Radiative Transfer Simulations of Patchy Reionization

We present the first calculation of the kinetic Sunyaev-Zel'dovich (kSZ) effect due to the inhomogeneous reionization of the universe based on detailed large-scale radiative transfer simulations of reionization. The resulting sky power spectra peak at l=2000-8000 with maximum values of l^2C_l~1\times10^{-12}. The peak scale is determined by the typical size of the ionized regions and roughly corresponds to the ionized bubble sizes observed in our simulations, ~5-20 Mpc. The kSZ anisotropy signal from reionization dominates the primary CMB signal above l=3000. This predicted kSZ signal at arcminute scales is sufficiently strong to be detectable by upcoming experiments, like the Atacama Cosmology Telescope and South Pole Telescope which are expected to have ~1' resolution and ~muK sensitivity. The extended and patchy nature of the reionization process results in a boost of the peak signal in power by approximately one order of magnitude compared to a uniform reionization scenario, while roughly tripling the signal compared with that based upon the assumption of gradual but spatially uniform reionization. At large scales the patchy kSZ signal depends largely on the ionizing source efficiencies and the large-scale velocity fields: sources which produce photons more efficiently yield correspondingly higher signals. The introduction of sub-grid gas clumping in the radiative transfer simulations produces significantly more power at small scales, and more non-Gaussian features, but has little effect at large scales. The patchy nature of the reionization process roughly doubles the total observed kSZ signal for l~3000-10^4 compared to non-patchy scenarios with the same total electron-scattering optical depth.Comment: 14 pages, 13 figures (some in color), submitted to Ap

Modeling Global Warming Scenarios in Greenback Cutthroat Trout (\u3cem\u3eOncorhynchus Clarki Stomias\u3c/em\u3e) Streams: Implications for Species Recovery

Changes in global climate may exacerbate other anthropogenic stressors, accelerating the decline in distribution and abundance of rare species throughout the world. We examined the potential effects of a warming climate on the greenback cutthroat trout (Oncorhynchus clarki stomias), a resident salmonid that inhabits headwater streams of the central Rocky Mountains. Greenbacks are outcompeted at lower elevations by nonnative species of trout and currently are restricted to upper-elevation habitats where barriers to upstream migration by nonnatives are or have been established. We used likelihood-based techniques and information theoretics to select models predicting stream temperature changes for 10 streams where greenback cutthroat trout have been translocated. These models showed high variability among responses by different streams, indicating the usefulness of a stream-specific approach. We used these models to project changes in stream temperatures based on 2°C and 4°C warming of average air temperatures. In these warming scenarios, spawning is predicted to begin from 2 to 3.3 weeks earlier than would be expected under baseline conditions. Of the 10 streams used in this assessment, 5 currently have less than a 50% chance of translocation success. Warming increased the probability of translocation success in these 5 streams by 11.2% and 21.8% in the 2 scenarios, respectively. Assuming barriers to upstream migration by nonnative competitors maintain their integrity, we conclude that an overall habitat improvement results because greenbacks have been restricted through competition with nonnatives to suboptimal habitats, which are generally too cold to be highly productive

Charge-based interaction conserved within histone H3 lysine 4 (H3K4) methyltransferase complexes is needed for protein stability, histone methylation, and gene expression

Histone H3 lysine 4 (H3K4) methyltransferases are conserved from yeast to humans, assemble in multisubunit complexes, and are needed to regulate gene expression. The yeast H3K4 methyltransferase complex, Set1 complex or complex of proteins associated with Set1 (COMPASS), consists of Set1 and conserved Set1-associated proteins: Swd1, Swd2, Swd3, Spp1, Bre2, Sdc1, and Shg1. The removal of the WD40 domain-containing subunits Swd1 and Swd3 leads to a loss of Set1 protein and consequently a complete loss ofH3K4methylation. However, until now, how these WD40 domain-containing proteins interact with Set1 and contribute to the stability of Set1 and H3K4 methylation has not been determined. In this study, we identified small basic and acidic patches that mediate protein interactions between theC terminus of Swd1 and the nSET domain of Set1. Absence of either the basic or acidic patches of Set1 and Swd1, respectively, disrupts the interaction between Set1 and Swd1, diminishes Set1 protein levels, and abolishesH3K4methylation. Moreover, these basic and acidic patches are also important for cell growth, telomere silencing, and gene expression. We also show that the basic and acidic patches of Set1 and Swd1 are conserved in their human counter-parts SET1A/B and RBBP5, respectively, and are needed for the protein interaction between SET1A and RBBP5. Therefore, this charge-based interaction is likely important for maintaining the protein stability of the human SET1A/B methyltransferase complexes so that proper H3K4 methylation, cell growth, and gene expression can also occur in mammals. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

Measurement of the Neutron Lifetime by Counting Trapped Protons in a Cold Neutron Beam

A measurement of the neutron lifetime $\tau_{n}$ performed by the absolute counting of in-beam neutrons and their decay protons has been completed. Protons confined in a quasi-Penning trap were accelerated onto a silicon detector held at a high potential and counted with nearly unit efficiency. The neutrons were counted by a device with an efficiency inversely proportional to neutron velocity, which cancels the dwell time of the neutron beam in the trap. The result is $\tau_{n} = (886.6\pm1.2{\rm [stat]}\pm3.2{\rm [sys]})$ s, which is the most precise measurement of the lifetime using an in-beam method. The systematic uncertainty is dominated by neutron counting, in particular the mass of the deposit and the $^{6}$Li({\it{n,t}}) cross section. The measurement technique and apparatus, data analysis, and investigation of systematic uncertainties are discussed in detail.Comment: 71 pages, 20 figures, 9 tables; submitted to PR