Juvenile CLN3 disease is a lysosomal cholesterol storage disorder: similarities with Niemann-Pick type C disease.

Background: The most common form of neuronal ceroid lipofuscinosis (NCL) is juvenile CLN3 disease (JNCL), a currently incurable neurodegenerative disorder caused by mutations in the CLN3 gene. Based on our previous work and on the premise that CLN3 affects the trafficking of the cation-independent mannose-6 phosphate receptor and its ligand NPC2, we hypothesised that dysfunction of CLN3 leads to the aberrant accumulation of cholesterol in the late endosomes/lysosomes (LE/Lys) of JNCL patients' brains.

Methods: An immunopurification strategy was used to isolate intact LE/Lys from frozen autopsy brain samples.

Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate.

The late endosome/lysosome (LE/Lys) lipid bis(monoacylglycero)phosphate (BMP) plays major roles in cargo sorting and degradation, regulation of cholesterol and intercellular communication and has been linked to viral infection and neurodegeneration. Although BMP was initially described over fifty years ago, the enzymes regulating its synthesis remain unknown. The first step in the BMP biosynthetic pathway is the conversion of phosphatidylglycerol (PG) into lysophosphatidylglycerol (LPG) by a phospholipase A2 (PLA2) enzyme.

Triplication of in Alzheimer's Disease Pathology in Down Syndrome.

Down Syndrome (DS), caused by triplication of human chromosome 21 (Hsa21) is the most common form of intellectual disability worldwide. Recent progress in healthcare has resulted in a dramatic increase in the lifespan of individuals with DS. Unfortunately, most will develop Alzheimer's disease like dementia (DS-AD) as they age.

Proteomic fingerprinting of Neotropical hard tick species (Acari: Ixodidae) using a self-curated mass spectra reference library.

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry is an analytical method that detects macromolecules that can be used for proteomic fingerprinting and taxonomic identification in arthropods. The conventional MALDI approach uses fresh laboratory-reared arthropod specimens to build a reference mass spectra library with high-quality standards required to achieve reliable identification. However, this may not be possible to accomplish in some arthropod groups that are difficult to rear under laboratory conditions, or for which only alcohol preserved samples are available.

Asymmetry and bifurcations in three-dimensional sudden-contraction channel flows.

This study reports the presence of two different stable modes of bifurcation in the near field of a three-dimensional sudden contraction. To be precise, flow downstream of a symmetric sudden contraction undergoes a transition from a symmetric state to an asymmetric state through a symmetry-breaking pitchfork bifurcation following an increase in the channel aspect ratio or the Reynolds number. In addition, the oncoming (upstream) symmetry-plane flow exhibits spanwise bifurcations along the topological core lines of each of the salient roof and floor eddies.

Surface self-organization caused by dislocation networks.

We report a new mechanism of self-organization that can lead to robust surface ordering. We have quantitatively analyzed the thermal motion of holes created by sulfur atoms in a silver monolayer on a ruthenium surface, which we observed in real time with scanning tunneling microscopy. We find that the stability of the array of holes is determined by the arrangement and structure of misfit dislocations in the film.

Three-dimensional simulation of square jets in cross-flow.

Direct numerical simulations are performed to predict the three-dimensional unsteady flow interactions in the near-field of a square jet issuing normal to a cross-flow. The simulated flow features reveal the formation of an upstream horseshoe vortex system, which is the result of an interaction between the oncoming channel floor shear layer and the transverse jet; the growth of a sequence of Kelvin-Helmholtz instability-induced vortical rollers in the mixing layer between the jet and the cross-flow, which wrap around the front side of the jet; and the inception process of the counter-rotating vortex pair (CVP), which is initiated through the folding of the lateral jet shear layers. It has been observed that for a square jet in cross-flow, the developed Kelvin-Helmholtz instability induced shear layer rollers do not form closed circumferential vortex rings.

Interaction of trailing vortices in the wake of a wall-mounted rectangular cylinder.

Numerical simulations are performed to investigate three-dimensional unsteady vortex-vortex and vortex-surface interactions in the near field of a wall-mounted rectangular cylinder placed inside a channel. The generation mechanism of the upstream and the trailing vortices from the topologically important critical points and their near-wall evolution pattern have been examined in detail. In the upstream region, a laminar necklace vortex system formed around the junction between the rectangular block (cylinder) and the flat channel floor.

Spanwise bifurcation in plane-symmetric sudden-expansion flows.

Present computational investigation reports a steady bifurcation phenomenon for three-dimensional flows through a plane-symmetric sudden expansion. When the channel aspect ratio exceeds a critical value, the well-known step height (pitchfork) bifurcation evolves with different symmetry breaking orientations on the left and right sides of the channel and bifurcates in the spanwise direction. For the channel aspect ratio less than the critical value, the originally occurring spanwise bifurcation cannot be stably retained and evolves eventually to a step height bifurcation.