Telaprevir for Retreatment of HCV Infection Zeuzem, Stefan; Andreone, Pietro; Pol, Stanislas ...
New England journal of medicine/The New England journal of medicine,
06/2011, Volume:
364, Issue:
25
Journal Article
Peer reviewed
Open access
In patients with HCV infection who did not have a sustained response to peginterferon plus ribavirin, the addition of telaprevir to this combination therapy was more effective than combination ...therapy alone. Adverse events with telaprevir included rash and anemia.
Approximately 60% of patients who are infected with hepatitis C virus (HCV) genotype 1 are not cured by 48 weeks of peginterferon alfa combined with ribavirin.
1
Such patients fall into one of three categories: those who have no response to therapy, which is defined as a reduction of less than 2 log
10
in HCV RNA levels after 12 weeks of therapy
2
; those who have a partial response, which is defined as a reduction of at least 2 log
10
in a patient who has always had detectable serum HCV RNA during therapy; and those who have a relapse, . . .
In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together ...with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
New sets of parameters (“tunes”) for the underlying-event (UE) modelling of the
pythia
8,
pythia6
and
herwig++
Monte Carlo event generators are constructed using different parton distribution ...functions. Combined fits to CMS UE proton–proton (
p
p
) data at
s
=
7
TeV
and to UE proton–antiproton (
p
p
¯
) data from the CDF experiment at lower
s
, are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton–proton collisions at 13
TeV
. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to “minimum bias” (MB) events, multijet, and Drell–Yan (
q
q
¯
→
Z
/
γ
∗
→
lepton-antilepton+jets) observables at 7 and 8
TeV
, as well as predictions for MB and UE observables at 13
TeV
.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The recent approval of fungal carotenoids as food colorants by the European Union has strengthened the prospects for fungal cell factories for the production of polyketide pigments. Fungal production ...of colorants has the main advantage of making the manufacturer independent of the seasonal supply of raw materials, thus minimizing batch-to-batch variations. Here, we review the potential of polyketide pigments produced from chemotaxonomically selected non-toxigenic fungal strains (e.g. Penicillium and Epicoccum spp.) to serve as food colorants. We argue that the production of polyketide azaphilone pigments from such potentially safe hosts is advantageous over traditional processes that involve Monascus spp., which risks co-production of the mycotoxin citrinin. Thus, there is tremendous potential for the development of robust fungal production systems for polyketide pigments, both to tailor functionality and to expand the color palette of contemporary natural food colorants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of this study was to assess potential candidate gene regions and corresponding universal primer pairs as secondary DNA barcodes for the fungal kingdom, additional to ITS rDNA as primary ...barcode. Amplification efficiencies of 14 (partially) universal primer pairs targeting eight
genetic markers were tested across > 1 500 species (1 931 strains or specimens) and the outcomes of almost twenty thousand (19 577) polymerase chain reactions were evaluated. We tested several well-known primer pairs that amplify: i) sections of the nuclear ribosomal RNA gene large subunit
(D1-D2 domains of 26/28S); ii) the complete internal transcribed spacer region (ITS1/2); iii) partial β-tubulin II (TUB2); iv) γ-actin (ACT); v) translation elongation factor 1-α (TEF1α); and vi) the second largest subunit of RNA-polymerase
II (partial RPB2, section 5-6). Their PCR efficiencies were compared with novel candidate primers corresponding to: i) the fungal-specific translation elongation factor 3 (TEF3); ii) a small ribosomal protein necessary for t-RNA docking; iii) the 60S L10 (L1) RP;
iv) DNA topoisomerase I (TOPI); v) phosphoglycerate kinase (PGK); vi) hypothetical protein LNS2; and vii) alternative sections of TEF1α. Results showed that several gene sections are accessible to universal primers (or primers universal for phyla) yielding
a single PCR-product. Barcode gap and multi-dimensional scaling analyses revealed that some of the tested candidate markers have universal properties providing adequate infra- and inter-specific variation that make them attractive barcodes for species identification. Among these gene sections,
a novel high fidelity primer pair for TEF1α, already widely used as a phylogenetic marker in mycology, has potential as a supplementary DNA barcode with superior resolution to ITS. Both TOPI and PGK show promise for the Ascomycota, while TOPI and LNS2
are attractive for the Pucciniomycotina, for which universal primers for ribosomal subunits often fail.
Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental ...trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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