Ubiquitin ligase SMURF2 enhances epidermal growth factor receptor stability and tyrosine-kinase inhibitor resistance.

The discovery of activating epidermal growth factor receptor (EGFR) mutations spurred the use of EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, as the first-line treatment of lung cancers. We previously reported that differential degradation of TKI-sensitive ( L858R) and resistant (T790M) EGFR mutants upon erlotinib treatment correlates with drug sensitivity. We also reported that SMAD ubiquitination regulatory factor 2 (SMURF2) ligase activity is important in stabilizing EGFR.

Analysis of drug resistance mutations in pulmonary Mycobacterium tuberculosis isolates in the Southern coastal region of Andhra Pradesh, India.

Purpose And Objectives: Detection of drug resistance plays a crucial role in tuberculosis (TB) treatment and prevention of Mycobacterium tuberculosis (MTB) transmission. The aim of this study was to determine the levels and patterns of resistance of MTB isolates to two key anti-TB drugs (rifampicin, RIF and isoniazid, INH) and the type of mutations in drug resistance genes (rpoB, katG and inhA) of the isolates at the southern coastal region of Andhra Pradesh, India, using commercially available GenoType MTBDRplus assay under the Revised National TB Control Program.

Methods: GenoType MTBDRplus assay was performed on 2859 sputum smear-positive samples and the mutations in the genes responsible for resistance (rpoB, katG and inhA) were analyzed.

KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated β-TrCP1 degradation.

Attempts to target mutant KRAS have been unsuccessful. Here, we report the identification of Smad ubiquitination regulatory factor 2 (SMURF2) and UBCH5 as a critical E3:E2 complex maintaining KRAS protein stability. Loss of SMURF2 either by small interfering RNA/short hairpin RNA (siRNA/shRNA) or by overexpression of a catalytically inactive mutant causes KRAS degradation, whereas overexpression of wild-type SMURF2 enhances KRAS stability.

Tristetraprolin mediates radiation-induced TNF-α production in lung macrophages.

The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages.

Antimony-resistant but not antimony-sensitive Leishmania donovani up-regulates host IL-10 to overexpress multidrug-resistant protein 1.

The molecular mechanism of antimony-resistant Leishmania donovani (Sb(R)LD)-driven up-regulation of IL-10 and multidrug-resistant protein 1 (MDR1) in infected macrophages (Ms) has been investigated. This study showed that both promastigote and amastigote forms of Sb(R)LD, but not the antimony-sensitive form of LD, express a unique glycan with N-acetylgalactosamine as a terminal sugar. Removal of it either by enzyme treatment or by knocking down the relevant enzyme, galactosyltransferase in Sb(R)LD (KD Sb(R)LD), compromises the ability to induce the above effects.

Development of micro-shock wave assisted dry particle and fluid jet delivery system.

Small quantity of energetic material coated on the inner wall of a polymer tube is proposed as a new method to generate micro-shock waves in the laboratory. These micro-shock waves have been harnessed to develop a novel method of delivering dry particle and liquid jet into the target. We have generated micro-shock waves with the help of reactive explosive compound [high melting explosive (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) and traces of aluminium] coated polymer tube, utilising ∼9 J of energy.

Acidic pH induced STM1485 gene is essential for intracellular replication of Salmonella.

During the course of infection, Salmonella has to face several potentially lethal environmental conditions, one such being acidic pH. The ability to sense and respond to the acidic pH is crucial for the survival and replication of Salmonella. The physiological role of one gene (STM1485) involved in this response, which is upregulated inside the host cells (by 90- to 113-fold) is functionally characterized in Salmonella pathogenesis.

Needleless vaccine delivery using micro-shock waves.

Shock waves are one of the most efficient mechanisms of energy dissipation observed in nature. In this study, utilizing the instantaneous mechanical impulse generated behind a micro-shock wave during a controlled explosion, a novel nonintrusive needleless vaccine delivery system has been developed. It is well-known that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery.

Reliable means of diagnosis and serovar determination of blood-borne Salmonella strains: quick PCR amplification of unique genomic loci by novel primer sets.

Typhoid fever is becoming an ever increasing threat in the developing countries. We have improved considerably upon the existing PCR-based diagnosis method by designing primers against a region that is unique to Salmonella enterica subsp. enterica serovar Typhi and Salmonella enterica subsp.