Advances in RNA therapeutics for modulation of 'undruggable' targets.

Over the past decades, drug discovery utilizing small pharmacological compounds, fragment-based therapeutics, and antibody therapy have significantly advanced treatment options for many human diseases. However, a major bottleneck has been that>70% of human proteins/genomic regions are 'undruggable' by the above-mentioned approaches. Many of these proteins constitute essential drug targets against complex multifactorial diseases like cancer, immunological disorders, and neurological diseases.

The bacterial magnesium transporter MgtA reveals highly selective interaction with specific cardiolipin species.

The bacterial magnesium transporter A (MgtA) is a specialized P-type ATPase important for Mg import into the cytoplasm; disrupted magnesium homeostasis is linked to intrinsic ribosome instability and antibacterial resistance in Salmonella strains. Here, we show that MgtA has functional specificity for cardiolipin 18:1. Still, it reaches maximum activity only in combination with cardiolipin 16:0, equivalent to the major components of native cardiolipin found in E.

CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer.

CD8 T cells that express retinoic acid-related orphan receptor (ROR)γt (T17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8RORγt T cells (T17 cells) was increased in peripheral blood.

The magnesium transporter A is activated by cardiolipin and is highly sensitive to free magnesium in vitro.

The magnesium transporter A (MgtA) is a specialized P-type ATPase, believed to import Mg(2+) into the cytoplasm. In Salmonella typhimurium and Escherichia coli, the virulence determining two-component system PhoQ/PhoP regulates the transcription of mgtA gene by sensing Mg(2+) concentrations in the periplasm. However, the factors that affect MgtA function are not known.

Functional characterization of a new holin-like antibacterial protein coding gene tmp1 from goat skin surface metagenome.

We have identified a holin-like gene from a goat skin surface metagenome. The ORF designated tmp1 coding for 34 amino acids shared sequence similarity with putative holin-like toxin genes. To analyze the antibacterial activity of tmp1 encoded protein, this ORF was cloned and expressed in Escherichia coli BL21(DE3).