Molecular basis for transposase activation by a dedicated AAA+ ATPase.

Transposases drive chromosomal rearrangements and the dissemination of drug-resistance genes and toxins. Although some transposases act alone, many rely on dedicated AAA+ ATPase subunits that regulate site selectivity and catalytic function through poorly understood mechanisms. Using IS21 as a model transposase system, we show how an ATPase regulator uses nucleotide-controlled assembly and DNA deformation to enable structure-based site selectivity, transposase recruitment, and activation and integration.

IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings.

Transposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transposase present in the widespread IS21 family of mobile elements, catalyzes efficient DNA transposition. Solution studies show that IstA engages the transposon terminal sequences to form a high-molecular weight complex and promote DNA integration.

The type V myosin-containing complex HUM is a RAB11 effector powering movement of secretory vesicles.

In the apex-directed RAB11 exocytic pathway of , kinesin-1/KinA conveys secretory vesicles (SVs) to the hyphal tip, where they are transferred to the type V myosin MyoE. MyoE concentrates SVs at an apical store located underneath the PM resembling the presynaptic active zone. A rod-shaped RAB11 effector, UDS1, and the intrinsically disordered and coiled-coil HMSV associate with MyoE in a stable HUM (HMSV-UDS1-MyoE) complex recruited by RAB11 to SVs through an interaction network involving RAB11 and HUM components, with the MyoE globular tail domain (GTD) binding both HMSV and RAB11-GTP and RAB11-GTP binding both the MyoE-GTD and UDS1.

Improved cancer-related fatigue in a randomised clinical trial: methylphenidate no better than placebo.

Introduction: Methylphenidate is a psychostimulant drug used to treat fatigue in patients with advanced cancer, for which there is no gold standard of treatment.

Objective: To explore the efficacy of methylphenidate in the relief of fatigue in patients with advanced cancer.

Materials And Methods: A randomised double-blind placebo-controlled multicentre clinical trial, stratified according to the intensity of fatigue.

Prevalence and characterization of breakthrough pain in patients with cancer in Spain: the CARPE-DIO study.

We aimed to evaluate the prevalence, characteristics and impact of breakthrough pain (BTP) in patients with cancer attending the main specialties involved in the diagnosis and management of BTP in Spain using a multicenter, observational, cross-sectional, multidisciplinary study. Investigators had to record all patients seen at the clinic during 1 month, determine whether the patients had cancer pain, and apply the Davies algorithm to ascertain whether the patients were suffering from BTP. Of the 3,765 patients with cancer, 1,117 (30%) had cancer-related pain, and of these patients, 539 had BTP (48%, 95%CI:45-51).