Evaluating the druggability of TrmD, a potential antibacterial target, through design and microbiological profiling of a series of potent TrmD inhibitors.

The post-transcriptional modifier tRNA-(N1G37) methyltransferase (TrmD) has been proposed to be essential for growth in many Gram-negative and Gram-positive pathogens, however previously reported inhibitors show only weak antibacterial activity. In this work, optimisation of fragment hits resulted in compounds with low nanomolar TrmD inhibition incorporating features designed to enhance bacterial permeability and covering a range of physicochemical space. The resulting lack of significant antibacterial activity suggests that whilst TrmD is highly ligandable, its essentiality and druggability are called into question.

Generating the curvature perturbation at the end of inflation in string theory.

In brane inflationary scenarios, the cosmological perturbations are supposed to originate from the vacuum fluctuations of the inflaton field corresponding to the position of the brane. We show that a significant, and possibly dominant, contribution to the curvature perturbation is generated at the end of inflation through the vacuum fluctuations of fields, other than the inflaton, which are light during the inflationary trajectory and become heavy at the brane-antibrane annihilation. These fields appear generically in string compactifications where the background geometry has exact or approximate isometries and parametrize the internal angular directions of the brane.

Inflationary prediction for primordial non-gaussianity.

We extend the deltaN formalism so that it gives all of the stochastic properties of the primordial curvature perturbation zeta if the initial field perturbations are Gaussian. The calculation requires only the knowledge of some family of unperturbed universes. A formula is given for the normalization f(NL) of the bispectrum of zeta, which is the main signal of non-Gaussianity. Examples of the use of the formula are given, and its relation to cosmological perturbation theory is explained.