DNase Sda1 Allows Invasive M1T1 Group A Streptococcus to Prevent TLR9-Dependent Recognition

Group A Streptococcus (GAS) has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase

Cassini Radio Science

Cassini radio science investigations will be conducted both during the cruise (gravitational wave and conjunction experiments) and the Saturnian tour of the mission (atmospheric and ionospheric occultations, ring occultations, determinations of masses and gravity fields). New technologies in the construction of the instrument, which consists of a portion on-board the spacecraft and another portion on the ground, including the use of the Ka-band signal in addition to that of the S- and X-bands, open opportunities for important discoveries in each of the above scientific areas, due to increased accuracy, resolution, sensitivity, and dynamic range.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43765/1/11214_2004_Article_1436.pd

Design and prototype manufacturing of a torque measurement system

In the present day, automobile manufacturers demand a certain torque range from hinges provided by supply industry. However, there are no torque measurement system used by the industry to measure this kind of mechanisms and the available systems cannot meet expectations. The purpose of this study is to design a computer-based torque measurement system and to produce its prototype. This system will be used to measure torque range of the vehicle front hood hinges and to control whether torque value is suitable or not. The developed system is an integrated mechatronic system that contains such subsystems as mechanical, electronic and control system. It is expected that the developed torque measurement system will fill an important gap in the relevant industrial sectors and will find widespread application area

Ubiquitinomics: History, methods, and applications in basic research and drug discovery

The ubiquitin-proteasome system (UPS) was discovered about 40 years ago and is known to regulate a multitude of cellular processes including protein homeostasis. Ubiquitylated proteins are recognized by downstream effectors, resulting in alterations of protein abundance, activity, or localization. Not surprisingly, the ubiquitylation machinery is dysregulated in numerous diseases, including cancers and neurodegeneration. Mass spectrometry (MS)-based proteomics has emerged as a transformative technology for characterizing protein ubiquitylation in an unbiased fashion. Here, we provide an overview of the different MS-based approaches for studying protein ubiquitylation. We review various methods for enriching and quantifying ubiquitin modifications at the peptide or protein level, outline MS acquisition, and data processing approaches and discuss key challenges. Finally, we examine how MS-based ubiquitinomics can aid both basic biology and drug discovery research