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result(s) for
"Brand, William R"
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Truth, errors, and lies
Grzegorz W. Kolodko, one of the world's leading authorities on economics and development policy and a key architect of Poland's successful economic reforms, applies his far-reaching knowledge to the past and future of the world economy, introducing a framework for understanding our global situation that transcends any single discipline or paradigm.
eBook
His Clement Highness
I had thought whatever humor there was to be mined in Ethiopia had been exhausted by Evelyn Waugh. Not so: his report of the coronation of Haile Selassie in 1930, preserved in \"When the Going Was Good,\" is one of the splendors of modern travel writing, but it is the view of an outsider who saw the occasion as an Alice-in-Wonderland affair. Ryszard Kapuscinski, a Polish journalist, offers us the other end of his reign: the calcification and collapse of the emperor's 44-year regime as observed by the palace familiars.
Magazine Article
A War With Weekends Off
Surely Ryszard Kapuscinski's specialty is as rarefied as any in journalism. He writes about the death of imperial regimes. There was quite a lot of that going on in the '70s and Kapuscinski seems always to have been present: an invisible witness to Haile Selassie's fall in Ethiopia, on the scene when the shah fell in Iran.
Magazine Article
The pathobiology of human fungal infections
Human fungal infections are a historically neglected area of disease research, yet they cause more than 1.5 million deaths every year. Our understanding of the pathophysiology of these infections has increased considerably over the past decade, through major insights into both the host and pathogen factors that contribute to the phenotype and severity of these diseases. Recent studies are revealing multiple mechanisms by which fungi modify and manipulate the host, escape immune surveillance and generate complex comorbidities. Although the emergence of fungal strains that are less susceptible to antifungal drugs or that rapidly evolve drug resistance is posing new threats, greater understanding of immune mechanisms and host susceptibility factors is beginning to offer novel immunotherapeutic options for the future. In this Review, we provide a broad and comprehensive overview of the pathobiology of human fungal infections, focusing specifically on pathogens that can cause invasive life-threatening infections, highlighting recent discoveries from the pathogen, host and clinical perspectives. We conclude by discussing key future challenges including antifungal drug resistance, the emergence of new pathogens and new developments in modern medicine that are promoting susceptibility to infection.In this Review, Brown et al. provide an overview of fungal pathobiology from the pathogen, host and clinical perspectives, focusing specifically on pathogens that can cause invasive life-threatening infections.
Journal Article
Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease
Elaine Remmers and colleagues report a genome-wide association study for Behçet's Disease in a Turkish population. They identify associations in the Class I region of the MHC,
IL10
and
IL23R-IL12RB2
.
Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with
HLA-B*51
and identified a second, independent association within the MHC Class I region. We also identified an association at
IL10
(rs1518111,
P
= 1.88 × 10
−8
). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at
IL10
(rs1518111,
P
= 3.54 × 10
−18
, odds ratio = 1.45, 95% CI 1.34–1.58) and the
IL23R
-
IL12RB2
locus (rs924080,
P
= 6.69 × 10
−9
, OR = 1.28, 95% CI 1.18–1.39). The disease-associated
IL10
variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.
Journal Article
The origin of the odorant receptor gene family in insects
The origin of the insect odorant receptor (OR) gene family has been hypothesized to have coincided with the evolution of terrestriality in insects. Missbach et al. (2014) suggested that ORs instead evolved with an ancestral OR co-receptor (Orco) after the origin of terrestriality and the OR/Orco system is an adaptation to winged flight in insects. We investigated genomes of the Collembola, Diplura, Archaeognatha, Zygentoma, Odonata, and Ephemeroptera, and find ORs present in all insect genomes but absent from lineages predating the evolution of insects. Orco is absent only in the ancestrally wingless insect lineage Archaeognatha. Our new genome sequence of the zygentoman firebrat Thermobia domestica reveals a full OR/Orco system. We conclude that ORs evolved before winged flight, perhaps as an adaptation to terrestriality, representing a key evolutionary novelty in the ancestor of all insects, and hence a molecular synapomorphy for the Class Insecta.
Journal Article
Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic Pulmonary Fibrosis
Selective repression of the antifibrotic gene CXCL10 contributes to tissue remodeling in idiopathic pulmonary fibrosis (IPF). We have previously reported that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are involved in CXCL10 repression. In this study, we explored the role of H3K27 methylation and the interplay between the two histone lysine methyltransferases enhancer of zest homolog 2 (EZH2) and G9a in CXCL10 repression in IPF. By applying chromatin immunoprecipitation, Re-ChIP, and proximity ligation assays, we demonstrated that, like G9a-mediated H3K9 methylation, EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3) was significantly enriched at the CXCL10 promoter in fibroblasts from IPF lungs (F-IPF) compared with fibroblasts from nonfibrotic lungs, and we also found that EZH2 and G9a physically interacted with each other. EZH2 knockdown reduced not only EZH2 and H3K27me3 but also G9a and H3K9me3, and G9a knockdown reduced not only G9 and H3K9me3 but also EZH2 and H3K27me3. Depletion and inhibition of EZH2 and G9a also reversed histone deacetylation and restored CXCL10 expression in F-IPF. Furthermore, treatment of fibroblasts from nonfibrotic lungs with the profibrotic cytokine transforming growth factor-β1 increased EZH2, G9a, H3K27me3, H3K9me3, and histone deacetylation at the CXCL10 promoter, similar to that observed in F-IPF, which was correlated with CXCL10 repression and was prevented by EZH2 and G9a knockdown. These findings suggest that a novel and functionally interdependent interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay may prove to be a target for epigenetic intervention to restore the expression of CXCL10 and other antifibrotic genes in IPF.
Journal Article