Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear

Particle-in-cell Simulations of Firehose Instability Driven by Bi-Kappa Electrons

We report the first results from particle-in-cell simulations of the fast-growing aperiodic electron firehose instability driven by the anisotropic bi-Kappa distributed electrons. Such electrons characterize space plasmas, e.g., solar wind and planetary magnetospheres. Predictions made by the linear theory for full wave-frequency and wavevector spectra of instabilities are confirmed by the simulations showing that only the aperiodic branch develops at oblique angles with respect to the magnetic field direction. Angles corresponding to the peak magnetic field fluctuating power spectrum increase with the increase in the anisotropy and with the decrease in the inverse powerlaw index κ. The instability saturation and later nonlinear evolutions are also dominated by the oblique fluctuations, which are enhanced by the suprathermals and trigger a faster relaxation of the anisotropic electrons. Diffusion in velocity space is stimulated by the growing fluctuations, which scatter the electrons, starting with the more energetic suprathermal populations, as appears already before the saturation. After saturation the fluctuating magnetic field power shows decay patterns in the wave-vector space and a shift toward lower angles of propagation.status: publishe

Asymmetry in catalysis by Thermotoga maritima membrane-bound pyrophosphatase demonstrated by a nonphosphorus allosteric inhibitor

Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyze pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and parasitic protists, but no homologous proteins exist in vertebrates, making them a promising drug target. Here, we report the first nonphosphorus allosteric inhibitor of the thermophilic bacterium Thermotoga maritima membrane-bound pyrophosphatase and its bound structure together with the substrate analog imidodiphosphate. The unit cell contains two protein homodimers, each binding a single inhibitor dimer near the exit channel, creating a hydrophobic clamp that inhibits the movement of beta-strand 1-2 during pumping, and thus prevents the hydrophobic gate from opening. This asymmetry of inhibitor binding with respect to each homodimer provides the first clear structural demonstration of asymmetry in the catalytic cycle of membrane-bound pyrophosphatases.Peer reviewe