Biological Roles of the Podospora anserina Mitochondrial Lon Protease and the Importance of Its N-Domain

Mitochondria have their own ATP-dependent proteases that maintain the functional state of the organelle. All multicellular eukaryotes, including filamentous fungi, possess the same set of mitochondrial proteases, unlike in unicellular yeasts, where ClpXP, one of the two matricial proteases, is absent. Despite the presence of ClpXP in the filamentous fungus Podospora anserina, deletion of the gene encoding the other matricial protease, PaLon1, leads to lethality at high and low temperatures, indicating that PaLON1 plays a main role in protein quality control. Under normal physiological conditions, the PaLon1 deletion is viable but decreases life span. PaLon1 deletion also leads to defects in two steps during development, ascospore germination and sexual reproduction, which suggests that PaLON1 ensures important regulatory functions during fungal development. Mitochondrial Lon proteases are composed of a central ATPase domain flanked by a large non-catalytic N-domain and a C-terminal protease domain. We found that three mutations in the N-domain of PaLON1 affected fungal life cycle, PaLON1 protein expression and mitochondrial proteolytic activity, which reveals the functional importance of the N-domain of the mitochondrial Lon protease. All PaLon1 mutations affected the C-terminal part of the N-domain. Considering that the C-terminal part is predicted to have an α helical arrangement in which the number, length and position of the helices are conserved with the solved structure of its bacterial homologs, we propose that this all-helical structure participates in Lon substrate interaction

Roles of fibroblast growth factors in the inner ear

The basic biology of the fibroblast growth factor (FGF) receptors and their splice variants is first reviewed, followed by a review of the known roles of FGFs in the inner ear. They include induction of the otocyst by FGF19, followed by FGF3 in further development of the otocyst. In later development, FGF3 or FGF10 acting on FGF receptor 2b is likely to be involved in development of the walls of the cochlear spaces, while FGF receptor 3 is involved in differentiation of the pillar cells of the organ of Corti. FGF1 and FGF2 act as trophic factors for the developing cochlear nerve fibres. Copyright (C) 2002 S. Karger AG, Basel

Porous Ni/ZrO2 Cermet from Highly Concentrated Composite Colloid

Rheology and shaping of concentrated cermet suspensions consisting of nickel (Ni) and yttria-stabilized zirconia (YSZ) nanoparticles in water have been examined over a broad range of volumetric solids concentration (ϕ = 0.1–0.4) and Ni fraction (fNi = 0.15–0.45). Preferential adsorption of pyrogallol-poly(ethylene glycol) polymer (i.e., Gallol-PEG) on surface of the Ni and YSZ particles imparts steric hindrance between the suspending particles so that fluidity can be obtained under shear stress. The cermet suspensions exhibit shear-thinning flow behavior under steady-shear measurement over shear rates of 100–103 s−1. Yield stress and yield strain of the suspensions appear to vary pronouncedly with ϕ and fNi under oscillatory shear over a shear-strain range of 10−1–103%. With the Gallol-PEG adsorption, an apparent viscosity less than 6 × 10−1 Pa.s at a shear rate of 102 s−1 has been obtained for the highly concentrated composite suspension with ϕ of 0.40 and fNi of 0.25. A high solids concentration effectively prohibits phase segregation during wet-shaping processes. Uniform green compacts have been obtained from slip casting of the concentrated cermet mixture (ϕ = 0.30) without use of binder and are then fired at 1200°C under reducing atmosphere to form porous Ni/YSZ compacts. Relative sintered density increases from 65% to 75% of the theoretical value when fNi was increased from 0.15 to 0.45, due mainly to the lower sintering temperature required for the Ni phase

Electrophysiological confirmation of the zona incerta as a target for surgical treatment of disabling involuntary arm movements in multiple sclerosis: use of local field potentials.

Lesioning or chronic deep brain stimulation (DBS) of the nucleus ventralis intermedius results in abolition of tremor in the contralateral limbs in Parkinson's disease (PD) and also in essential tremor. Recently, chronic DBS of the subthalamic nucleus has also proved to be very effective in reducing contralateral limb tremor in PD. These targets have been less effective in controlling the complex limb tremor often seen in multiple sclerosis (MS). Consequently, other targets have been sought in cases of MS with tremor. We describe a patient with MS with disabling proximal and distal involuntary arm movements in whom we were able to obtain sustained control of contralateral arm tremor and achieve functional improvement of the affected arm by chronic DBS of the region of the zona incerta. We also highlight the important role played by local field potentials recorded from the brain, with simultaneous recording of corresponding EMGs, in target localisation