Is the eye a window to the brain in Sanfilippo syndrome?

Published online: 17 November 2020Sanfilippo syndrome is an untreatable form of childhood-onset dementia. Whilst several therapeutic strategies are being evaluated in human clinical trials including i.v. delivery of AAV9-based gene therapy, an urgent unmet need is the availability of non-invasive, quantitative measures of neurodegeneration. We hypothesise that as part of the central nervous system, the retina may provide a window through which to 'visualise' degenerative lesions in brain and amelioration of them following treatment. This is reliant on the age of onset and the rate of disease progression being equivalent in retina and brain. For the first time we have assessed in parallel, the nature, age of onset and rate of retinal and brain degeneration in a mouse model of Sanfilippo syndrome. Significant accumulation of heparan sulphate and expansion of the endo/lysosomal system was observed in both retina and brain pre-symptomatically (by 3 weeks of age). Robust and early activation of micro- and macroglia was also observed in both tissues. There was substantial thinning of retina and loss of rod and cone photoreceptors by ~ 12 weeks of age, a time at which cognitive symptoms are noted. Intravenous delivery of a clinically relevant AAV9-human sulphamidase vector to neonatal mice prevented disease lesion appearance in retina and most areas of brain when assessed 6 weeks later. Collectively, the findings highlight the previously unrecognised early and significant involvement of retina in the Sanfilippo disease process, lesions that are preventable by neonatal treatment with AAV9-sulphamidase. Critically, our data demonstrate for the first time that the advancement of retinal disease parallels that occurring in brain in Sanfilippo syndrome, thus retina may provide an easily accessible neural tissue via which brain disease development and its amelioration with treatment can be monitored.Helen Beard, Glyn Chidlow, Daniel Neumann, Nazzmer Nazri, Meghan Douglass, Paul J. Trim, Marten F. Snel, Robert J. Casson and Kim M. Hemsle

Impacts of Imazapyr and Triclopyr Soil Residues on the Growth of Several Restoration Species

Herbicides are frequently used in natural systems to control invasive plants, but nontarget impacts from persistent soil residues can result in unintended ecosystem effects. Imazapyr and triclopyr are herbicides that are widely used in noncrop areas such as rangelands to manage perennial weeds, especially woody species such as tamarisk (saltcedar). Due to widespread environmental and anthropogenic changes in the American southwest, tamarisk, which is commonly thought to co-occur only with riparian plants, is increasingly being found in communities of upland rangeland species. Using an in vitro study combined with high-performance liquid chromatography (HPLC) analyses, imazapyr and triclopyr degradation rates were determined in six Colorado soils. In addition, the relative sensitivity of desirable species to the two herbicides was determined in a field dose response study. Exponential decay models estimated that triclopyr degradation (half-lives of 5-16 days) was 20 times more rapid than imazapyr degradation (half-lives of 82-268 days). All species tested were sensitive to imazapyr residues, but the degree of sensitivity was strongly dependent on soil properties. Sensitive species (alkali sacaton and western wheatgrass) were tolerant of imazapyr residues in some soils 20-23 months after applications. Relatively insensitive species (slender wheatgrass) were tolerant of imazapyr residues in the same soils 10 months after applications. American licorice was sensitive to triclopyr residues up to 89 days after applications, and several grasses (including sideoats grama) showed minor sensitivity. Our study indicates that there is an interaction between the spatial variability in herbicide degradation driven by edaphic properties and the sensitivity of plants to a herbicide, which could be exploited by management practitioners to aid in site rehabilitation. Specifically, managers could stagger planting of species temporally on the basis of their sensitivity to herbicide residues or could target areas of treated sites for planting that are known to have soil types facilitating relatively rapid herbicide degradation. © 2016 The Society for Range Management. Published by Elsevier Inc. All rights reserved.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information

New Large Leptictid Insectivore from the Late Paleogene of South Dakota, USA

From a skull and mandible, we describe a new genus and species of a primitive insectivore (Mammalia: Insectivora: Leptictida: Leptictidae). Its large body size and higher−crowned teeth indicate a different feeding ecology from other leptictid insectivores. With evidence of some heavy, flat wear on the molariform teeth, its shift in diet was likely to greater herbivory. Unlike the narrow snout of Blacktops, this new leptictid retains a broad snout, suggesting that small vertebrates were still important dietary components. The specimen was collected from the floodplain deposits of the lower or middle White River Group of South Dakota, which represent the latest Eocene to earliest Oligocene (Chadronian and Orellan North American Land Mammal “Ages”)