Two new variants of the lipocalin allergen Bos d 2

Allergens from various sources have been shown to comprise several isoforms. In the present study, a series of chromatographic steps was carried out to separate the lipocalin allergen Bos d 2 isoforms present in cow dander. Subsequent HPLC-MS–MS analyses revealed two new Bos d 2 variants. In one of the proteins, tyrosine (Y83) was substituted by aspartic acid, and in the other protein valine (V102) was replaced by alanine. We propose the three Bos d 2 variants be named as Bos d 2.0101 (previously sequenced Bos d 2), Bos d 2.0102 and Bos d 2.0103. Our results suggest that molecular polymorphism is a common property among lipocalin allergens. Since allergen isoforms may show variation in their IgE binding and/or T-cell reactivity, all of the many allergen forms should be taken into account when planning preparations for immunotherapy.     

Are Global and Regional Improvements in Life Expectancy and in Child,Adult and Senior Survival Slowing?

Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year²; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year²; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year². Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year². Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest.     

Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses

1. Download : Download high-res image (157KB)
2. Download : Download full-size image

     

Suppression of Viral RNA Binding and the Assembly of Infectious Hepatitis C Virus Particles In Vitro by Cyclophilin Inhibitors

Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable component of the HCV replication and assembly machineries. Although its precise mechanism of action is not yet clear, current evidence indicates that its structure and function are regulated by the cellular peptidylprolyl isomerase cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of NS5A, in a distributed fashion, and modulates the structure of the disordered domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA) and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in addition to their well-documented inhibitory effect on RNA replication. Although the interaction between NS5A and other viral proteins is not affected by CPIs, RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is significantly inhibited by CPI treatment, and sensitivity of RNA binding is correlated with previously characterized CyPA dependence or CsA sensitivity of HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic and a full-length replicon of JFH-1 was due, at least in part, to an additional role that CyPA plays in HCV assembly, a conclusion that is supported by experiments with the clinical CPI alisporivir. The host-directed nature and the ability to interfere with more than one step in the HCV life cycle may result in a higher genetic barrier to resistance for this class of HCV inhibitors.     

Narcolepsy

Narcolepsy is a disorder of sleep control characterized by a tetrad of symptoms: sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations. A diagnosis is made from a careful history. The incidence is estimated as high as 0.3% of the population. Unfortunately patients go for many years before the diagnosis is made and often have experienced disruption of their employment, social and family life, and may have experienced a number of car accidents because of falling asleep at the wheel. An unknown number of narcoleptics kill themselves on the highways before the diagnosis is ever made. Sleep attacks can usually be controlled by methylphenidate, and if the other symptoms persist they can often be effectively managed by imipramine.