“
“Yet unreported in this lysosomal storage disease, we aimed to quantify our observation that patients with fucosidosis may show abnormally increased cerebellar volumes during early childhood.

Five normocephalic fucosidosis patients (age range 2-25 months, three males) were included in this retrospective case control study. The CH5424802 mouse control cohort consisted of 25 children (age range 0-36 months, 15 males). Image postprocessing was performed independently by two radiologists. Using validated software, manual tracing of

contours on contiguous sagittal magnetic resonance images was allowed for cerebellar volumetry. We tested the null hypothesis that mean cerebellar volumes of four fucosidosis patients (age 16, 20, 21, and 25 months) and of an age-matched control ACY-738 ic50 cohort (n = 8, age range 13-26 months) were equal based on a two-tailed unpaired t-test.

Interobserver agreement was excellent (R = 1, p < 0.01). A rough trajectory of normal cerebellar development appeared to flatten around the age of 1 year. With mean volumes of 121.36 and 102.30 ml, respectively, cerebellar volumes of fucosidosis patients with a mean age of 21 months were significantly increased compared to age-matched controls (p < 0.05). In a single patient, longer-term follow-up with MRI at the age of 47 months was available and showed cerebellar atrophy.

Increased

cerebellar volume was shown to be an additional feature in the early stage of fucosidosis. EPZ004777 datasheet The combination

with a confirmed tendency toward atrophy of the cerebellum during later course of the disease is probably unique in the context of metabolic disorders of the brain.”
“Axl, a plasma membrane-associated Tyro3/Axl/Mer (TAM) family member, is necessary for optimal Zaire ebolavirus (ZEBOV) glycoprotein (GP)-dependent entry into some permissive cells but not others. To date, the role of Axl in virion entry is unknown. The focus of this study was to characterize entry pathways that are used for ZEBOV uptake in cells that require Axl for optimal transduction and to define the role of Axl in this process. Through the use of biochemical inhibitors, interfering RNA (RNAi), and dominant negative constructs, we demonstrate that ZEBOV-GP-dependent entry into these cells occurs through multiple uptake pathways, including both clathrin-dependent and caveola/lipid raft-mediated endocytosis. Other dynamin-dependent and -independent pathways such as macropinocytosis that mediate high-molecular-weight dextran uptake also stimulated ZEBOV-GP entry into these cells, and inhibitors that are known to block macropinocytosis inhibited both dextran uptake and ZEBOV infection. These findings provided strong evidence for the importance of this pathway in filovirus entry. Reduction of Axl expression by RNAi treatment resulted in decreased ZEBOV entry via macropinocytosis but had no effect on the clathrin-dependent or caveola/lipid raft-mediated endocytic mechanisms.