Towards understanding the epidemiology of Neisseria meningitidis in the African meningitis belt: a multi-disciplinary overview.

Objectives: Neisseria meningitidis is the major cause of seasonal meningitis epidemics in the African meningitis belt. In the changing context of a reduction in incidence of serogroup A and an increase in incidence of serogroups W and C and of Streptococcus pneumoniae, a better understanding of the determinants driving the disease transmission dynamics remains crucial to improving bacterial meningitis control.

Methods: The literature was searched to provide a multi-disciplinary overview of the determinants of meningitis transmission dynamics in the African meningitis belt.

Epidemiological impact and cost-effectiveness of universal vaccination with Bexsero(®) to reduce meningococcal group B disease in Germany.

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease.

Impact of America Invents Act on Biotech Intellectual Property.

This review introduces the America Invents Act (AIA), a comprehensive reform of U.S. law on patentability and patent enforceability that Congress enacted in 2011.

Introduction to Intellectual Property: A U.S. Perspective.

This review introduces patents and trade secrets, the two mechanisms that U.S. law provides inventors to protect their inventions.

Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy.

Objective: To investigate whether sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy (FSHD).

Methods: Sarcomeric function was evaluated by contractile studies on demembranated single muscle fibers obtained from quadriceps muscle biopsies of 4 patients with FSHD and 4 healthy controls. The sarcomere length dependency of force was determined together with measurements of thin filament length using immunofluorescence confocal scanning laser microscopy.

X-ray interference studies of crossbridge action in muscle contraction: evidence from quick releases.

We have used a high-resolution small angle X-ray scattering system, together with a high-performance CCD camera, on the BioCAT beamline at the APS synchrotron radiation facility at the Argonne National Laboratory, to study X-ray interference effects in the meridional reflections generated by the arrays of myosin crossbridges in contracting muscle. These give information about axial movements of the myosin heads during contraction with sub-nanometer resolution. Using whole intact muscle preparations (frog sartorius) we have been able to record the detailed behavior of M3 (the first order meridional reflection from the myosin crossbridges, at 14.

X-ray interference studies of crossbridge action in muscle contraction: evidence from muscles during steady shortening.

During normal muscle shortening, the myosin heads must undergo many cycles of interaction with the actin filaments sliding past them. It is important to determine what range of configurations is found under these circumstances, and, in terms of the tilting lever arm model, what range of orientations the lever arms undergo. We have studied this using the X-ray interference technique described in the previous article, focusing mainly on the changes in the first order meridional reflection (M3) as compared to isometric.

Structure-function relation of the myosin motor in striated muscle.

Force and shortening in striated muscle are driven by a structural working stroke in the globular portion of the myosin molecules-the myosin head-that cross-links the myosin-containing filaments and the actin-containing filaments. We use time-resolved X-ray diffraction in single fibers from frog skeletal muscle to link the conformational changes in the myosin head determined at atomic resolution in crystallographic studies with the kinetic and mechanical features of the molecular motor in the preserved sarcomeric structure. Our approach exploits the improved brightness and collimation of the X-ray beams of the third generation synchrotrons by using X-ray interference between the two arrays of myosin heads in each bipolar myosin filament to measure with A sensitivity the axial motions of myosin heads in situ during the synchronous execution of the working stroke elicited by rapid decreases in length or load imposed during an active isometric contraction.

X-ray diffraction studies of the contractile mechanism in single muscle fibres.

The molecular mechanism of muscle contraction was investigated in intact muscle fibres by X-ray diffraction. Changes in the intensities of the axial X-ray reflections produced by imposing rapid changes in fibre length establish the average conformation of the myosin heads during active isometric contraction, and show that the heads tilt during the elastic response to a change in fibre length and during the elementary force generating process: the working stroke. X-ray interference between the two arrays of myosin heads in each filament allows the axial motions of the heads following a sudden drop in force from the isometric level to be measured in situ with unprecedented precision.

Crystal structure of the actin binding domain of the cyclase-associated protein.

Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed beta-helix flanked by antiparallel beta-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface.

The myosin motor in muscle generates a smaller and slower working stroke at higher load.

Muscle contraction is driven by the motor protein myosin II, which binds transiently to an actin filament, generates a unitary filament displacement or 'working stroke', then detaches and repeats the cycle. The stroke size has been measured previously using isolated myosin II molecules at low load, with rather variable results, but not at the higher loads that the motor works against during muscle contraction. Here we used a novel X-ray-interference technique to measure the working stroke of myosin II at constant load in an intact muscle cell, preserving the native structure and function of the motor.

A versatile rapid-mixing and flow device for X-ray absorption spectroscopy.

A low-temperature rapid-mixing and flow system has been designed and implemented to monitor catalysis involving metal ions by X-ray absorption spectroscopy at the ID-18 beamline of the Advanced Photon Source, Argonne National Laboratory. The system will allow examination of biological metallo-intermediates at dilute metal ion concentrations by the detection of X-ray fluorescence. The instrument can be cooled to sub-zero temperatures, thus lengthening the life time of a reaction intermediate.