Gait analysis in a <i>Mecp2</i> knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the &lt;i&gt;Mecp2&lt;/i&gt; gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male &lt;i&gt;Mecp2&lt;/i&gt; knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of &lt;i&gt;Mecp2&lt;/i&gt;-dysfunction in future preclinical therapeutic studies

Quantifying the contribution of riparian total evaporation to streamflow transmission losses: Preliminary investigations along the Groot Letaba river

The Groot Letaba River, situated in the semi-arid north-eastern region of South Africa is an example of a river system in which the uncertainty associated with transmission losses (TL) has limited the effective management of environmental water requirement (EWR) flows. TL along the river significantly impacts EWR flows, as it is often the case that specified EWR releases are not adequately received further downstream. Due to the limited understanding of the magnitude of TL, as well as the dominant contributing processes to TL within the region, it remains a challenge to operate the river using downstream targets far from the source of operations. In an attempt to address this knowledge gap, detailed characterizations of hydrological processes were performed along the lower reaches of the river, which centred around the estimation of riparian total evaporation and quantifying the rapport between surface and subsurface water flow processes. Riparian total evaporation was estimated using the satellite-based surface energy balance system model, soil water evaporation measurements and open water evaporation estimates. Losses from the river to the adjacent aquifer were determined from the continuous monitoring of the groundwater phreatic surface and characterization of aquifer hydraulic properties. The results of these investigations indicated that present flows within the system are likely to be insufficient to satisfy gazetted median and extreme low flow targets. Overall, the study details key hydrological processes influencing TL along the river. It should, however, be noted that these observations only provide an understanding of the system over a limited observation period

The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease

The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD). Eighteen adults were randomised to receive 20g/day of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an inulin-control for 42-days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between groups (P=0.082), however IHCL significantly increased within the inulin-control group (20.9±2.9 to 26.8±3.9%; P=0.012; n=9), which was not observed within the IPE group (22.6±6.9 to 23.5±6.8%; P=0.635; n=9). The predominant SCFA from colonic fermentation of inulin is acetate, which in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate- mediated increase in IHC

Cyclotron resonance heating of a plasma in a magnetic "mirror" /

TID-4500, UC-20.Mode of access: Internet