Progressive neurodegeneration in aspartylglycosaminuria mice

Aspartylglycosaminuria (AGU) is one of the most common lysosomal storage disorders in humans. A mouse model for AGU has been recently generated through targeted disruption of the glycosylasparaginase gene, and at a young age the glycosyl asparaginase-deficient mice demonstrated many pathological changes found in human AGU patients (Kaartinen V, Mononen I, Voncken J-W, Gonzalez-Gomez I, Heisterkamp N, Groffen J: A mouse model for aspartylglycosaminuria. Nat Med 1996, 2:1375-1378). Our current findings demonstrate that after the age of 10 months, the general condition of null mutant mice gradually deteriorated. They suffered from a progressive motoric impairment and impaired bladder function and died prematurely. A widespread lysosomal hypertrophy in the central nervous system was detected. This neuronal vacuolation was particularly severe in the lateral thalamic nuclei, medullary reticular nuclei, vestibular nuclei, inferior olivary complex, and deep cerebellar nuclei. The oldest animals (20 months old) displayed a clear neuronal loss and gliosis, particularly in those regions, where the most severe vacuolation was found. The severe ataxic gait of the older mice was likely due to the dramatic loss of Purkinje cells, intensive astrogliosis and vacuolation of neurons in the deep cerebellar nuclei, and the severe vacuolation of the cells in vestibular and cochlear nuclei. The impaired bladder function and subsequent hydronephrosis were secondary to involvement of the central nervous system. These findings demonstrate that the glycosylasparaginase-deficient mice share many neuropathological features with human AGU patients, providing a suitable animal model to test therapeutic strategies in the treatment of the central nervous system effects in AGU.     

Synthesis and rheological properties of an associative star polymer in aqueous solutions

Rheological properties of aqueous solutions and hydrogels formed by an amphiphilic star block copolymer, poly(acrylic acid)-block-polystyrene (PAA₅₄-b-PS₆)₄, were investigated as a function of the polymer concentration (C_p), temperature, and added salt concentration. The water-soluble polymer synthesised by atom transfer radical polymerization (ATRP) was found to form hydrogels at room temperature at polymer concentrations, C_p, over 22 g/L due to the interpolymer hydrophobic association of the PS blocks. Increasing C_p leads to stronger elastic networks at room temperature that show a gel-to-solution transition with increasing temperature. Increase of ionic strength decreases the moduli compared with the pure hydrogel but did not affect the gel-sol transition temperature significantly. Small-angle X-ray experiments showed two distinct scattering correlation peaks for samples above the gelling C_p, which indicates the aggregates formed due to hydrophobic association. Upon heating the intensity of the scattering correlation peaks was found to decrease indicating the loss of the network structure due to thermal motion.     

Analysis of hexosaminitol-containing disaccharide alditols from rat brain glycoproteins and gangliosides as O-trimethylsilyl derivatives by gas chromatography mass spectrometry

The O-trimethylsilyl derivatives of five reference disaccharide alditols composed of a N-acetylhexosaminitol substituted at C-3, C-4 or C-6 with a hexose moiety were studied by gas chromatography mass spectrometry. The data were used in the determination of the linkage in disaccharide alditols derived from rat brain glycoproteins and gangliosides. The O-glycosidically linked carbohydrate units of brain glycoproteins contained two oligosaccharides, alpha-galactosyl-(1 leads to 3)-N-acetylgalactosaminitol and beta-galactosyl-(1 leads to 3)-N-acetylgalactosaminitol, whereas only the latter was obtained from brain gangliosides after partial acid hydrolysis and reduction.     

The impact of computer-mediated immediate feedback on developing oral presentation skills: An exploratory study in virtual reality

Feedback plays a central role in learning. Crucial to this is the nature and timing of the feedback. This experimental study explores the efficacy of immediate computer-mediated feedback within a virtual reality environment designed to facilitate the development of pre-university students' presentation skills. Two conditions were established to assess the efficacy: immediate computer-mediated feedback; a control condition of delayed expert-mediated feedback. Results showed improvement but no statistically relevant difference in performance gains between the two conditions, suggesting both can facilitate learning. Furthermore, students perceived the environment to be an effective and motivating platform in which to practise presentation skills. For educators seeking viable alternatives to face-to-face presentation practice and feedback, the finding that immediate computer-mediated feedback is potentially as effective in aiding presentation performance is crucial for two reasons: first, it expands practice opportunities for students; second, it could result in less pressure on resources, including time and staffing.     

Formation of thick dielectrophoretic carbon nanotube fibers

The aim of this work was to study the formation process of dielectrophoretic (DEP) carbon nanotube fibers (CNT-fibers) and characterize the fiber properties relevant to their technological applications. The fiber diameter was shown to increase when applied voltage was increased (up to 350 V(pp)) and when retraction speed was decreased (down from 400 μm s(-1)) in accordance with theoretical expectations. This paper represents the first demonstration of the formation of thick DEP CNT-fibers (up to ～ ?0.4 mm). This is an intriguing result, as it expands the diversity of possible applications of the fibers and facilitates their characterization by analytical methods that require large quantities of the material. The performance of these thick fibers was as follows: a density of ～ 0.35 g cm(-3), a tensile strength of ～ 15 MPa, a Young's modulus of ～ 1 GPa, and an electrical resistivity of ～ 70 mΩ cm.     

Recombinant human glycosylasparaginase catalyzes hydrolysis of L-asparagine

Cryptosporidium parvum causes persistent diarrhea in young children in developing countries. To determine the interaction between nutritional status and cryptosporidiosis, an open cohort of 1064 children younger than 3 y of age was followed for 1441 child-years by weekly diarrhea recall visits. A total of 5072 weight and 4264 height measurements was made. There were no tendencies of low weight (P = 0.38) or height (P = 0.16) in children who acquired cryptosporidiosis. Cryptosporidiosis in infancy was accompanied by an estimated weight loss of 392 g (95% CI: 247, 538 g) in boys and 294 g (95% CI: 109, 479 g) in girls, corresponding to 3.7% and 2.9% of mean weight, respectively, at 2 y of age. No significant catch-up growth covered for this loss in weight. A similar effect in linear growth was shown (P = 0.02). Although it has been suggested that the effect of infections on nutrition is usually transient because of catch-up growth, the present study suggests that cryptosporidiosis in infancy has a permanent effect on growth.     

Techno-economic evaluation of narrowband and broadband accessnetwork alternatives and evolution scenario assessment

The paper presents the main results obtained within the Research in Advanced Communications in Europe (RACE) project: 2087 TITAN regarding minimum-risk introductory routes for new narrowband and broadband services in the residential and small business market. The project developed a methodology and a tool for techno-economic evaluation of advanced narrowband and broadband telecommunications networks and services. Results from four extensive access network studies are presented. For the narrowband services, optical access and radio in the local loop have been assessed and compared to conventional copper layout in a greenfield environment. Access network upgrade strategies for emerging new broadband services have been evaluated in three studies, with technological options ranging from enhanced copper to hybrid-fiber-coax (HFC) and broadband passive optical networks. An extensive study on different broadband access network upgrade alternatives for public network operators (PNOs) were carried out, taking into account the diversity of conditions met today by European countries. In another study, the effect of competition In the access network was modeled assuming two main operators sharing the market. Broadband upgrade alternatives were evaluated for a new cable operator, competing with the dominant public network operator. In addition, video-on-demand (VoD) and Internet access upgrades have been analyzed. The paper demonstrates the viability of techno-economic studies for the access network, including in-depth analysis of the time-dependence of component cost, tariffs, service penetrations and market shares