Interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical regulator of inflammatory signalling through toll-like receptors 4 and 7/8 in murine and human lungs.

Background And Purpose: Toll-like receptors 4 (TLR4) and TLR7/TLR8 play an important role in mediating the inflammatory effects of bacterial and viral pathogens. Interleukin-1 receptor-associated kinase 4 (IRAK4) is an important regulator of signalling by toll-like receptor (TLR) and hence is a potential therapeutic target in diseases characterized by increased lung inflammatory signalling.

Experimental Approach: We used an established murine model of acute lung inflammation, and studied human lung tissue ex vivo, to investigate the effects of inhibiting IRAK4 on lung inflammatory pathways.

Discovery of a Novel Potent and Selective HSD17B13 Inhibitor, BI-3231, a Well-Characterized Chemical Probe Available for Open Science.

Genome-wide association studies in patients revealed HSD17B13 as a potential new target for the treatment of nonalcoholic steatohepatitis (NASH) and other liver diseases. However, the physiological function and the disease-relevant substrate of HSD17B13 remain unknown. In addition, no suitable chemical probe for HSD17B13 has been published yet.

Locking mixed-lineage kinase domain-like protein in its auto-inhibited state prevents necroptosis.

As an alternative pathway of controlled cell death, necroptosis can be triggered by tumor necrosis factor via the kinases RIPK1/RIPK3 and the effector protein mixed-lineage kinase domain-like protein (MLKL). Upon activation, MLKL oligomerizes and integrates into the plasma membrane via its executioner domain. Here, we present the X-ray and NMR costructures of the human MLKL executioner domain covalently bound via Cys86 to a xanthine class inhibitor.

Chemical Derivatization Enables MALDI-TOF-Based High-Throughput Screening for Microbial Trimethylamine (TMA)-Lyase Inhibitors.

Microbial-dependent trimethylamine (TMA) generation from dietary precursors such as choline was recently linked to cardiovascular diseases (CVDs) as well as chronic kidney disease (CKD). Inhibition of TMA-generating enzymes in gut bacteria would be an innovative approach to treat these diseases. The potential to accurately quantify secreted TMA levels highlights the capacity of mass spectrometry (MS) for tracking microbial TMA-lyase activity.

RapidFire BLAZE-Mode Is Boosting ESI-MS Toward High-Throughput-Screening.

Label-free in vitro potency assays are an emerging field in drug discovery to enable more physiological conditions, to improve the readout quality, and to save time. For this approach mass spectrometry (MS) is a powerful technology to directly follow physiological processes. The speed of this methodology, however, was for a long time not compatible with chemiluminescence- or fluorescence-based assays.

HIV-1 diversity, transmission dynamics and primary drug resistance in Angola.

Objectives: To assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up.

Methods: Population sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis.

Ectoparasite infestations of hedgehogs (Erinaceus europaeus) are associated with small-scale landscape structures in an urban-suburban environment.

Animals that exploit heterogeneous and patchy environments encounter different local habitat conditions that influence their interaction with the environment, such as the acquisition of parasites. How and at which scales interaction processes between parasites, hosts, and the environment are realized remains largely unknown. We examined the infestation patterns of 56 hedgehogs (Erinaceus europaeus) with fleas and ticks at a small spatial scale within a 12 km(2) area along a suburban-urban gradient in southwestern Germany.

Antiretroviral drug resistance surveillance among treatment-naive human immunodeficiency virus type 1-infected individuals in Angola: evidence for low level of transmitted drug resistance.

The prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease.

Characterization of a new sensitive PCR assay for quantification of viral DNA isolated from patients with hepatitis B virus infections.

Sensitive and accurate quantification of hepatitis B virus (HBV) DNA is necessary for monitoring patients with chronic hepatitis receiving antiviral therapy in order to determine treatment response and to adapt therapy in case of inadequate virologic control. The development of quantitative PCR assays has been crucial in meeting these needs. The objective of this study was to compare the performance of a new real-time PCR assay (Abbott RealTime) for HBV DNA with that of three other commercial assays for the detection of HBV DNA.

Cytomegalovirus quantification in plasma by an automated real-time PCR assay.

Background: Sensitive quantitation of cytomegalovirus (CMV) DNA in blood is helpful for the diagnosis of CMV infection or reactivation and the monitoring of transplanted patients.

Objectives: We compared a new PCR assay coupled with an automated extraction system (CMV real-time PCR, Abbott Molecular, Des Plaines, IL, USA) to a previously validated method (ultrasensitive Cobas Amplicor CMV DNA Monitor, Roche Molecular, Indianapolis, IN, USA).

Results: Using limiting dilutions of CMV DNA positive plasma, the two assays had a similar detection threshold ranging between 20 and 45 copies/ml.

Comparison of four commercial quantitative HIV-1 assays for viral load monitoring in clinical daily routine.

Background: Quantification of viral load (VL) is standard for monitoring HIV-1 therapy and is crucial before deciding whether to switch or to continue a current antiretroviral regimen.

Methods: We compared the performance of the four most widely used commercial viral-load assays, COBAS Amplicor Monitor v1.5, Versant HIV-1 RNA 3.

Performance of the automated Abbott RealTime HIV-1 assay on a genetically diverse panel of specimens from London: comparison to VERSANT HIV-1 RNA 3.0, AMPLICOR HIV-1 MONITOR v1.5, and LCx HIV RNA Quantitative assays.

Automated RNA extraction and quantitation of HIV-1 by real-time PCR offer potential advantages of efficient sample processing, improved sensitivity, expanded dynamic range and reduced contamination risk. In this study, plasma was collected from 100 HIV-1 infected patients visiting The Courtyard Clinic of St. George's Hospital in London, United Kingdom (UK).