Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy

Purpose: Recessive mutations in CLN7/MFSD8 usually cause variant late-infantile onset neuronal ceroid lipofuscinosis (vLINCL), a poorly understood neurodegenerative condition, though mutations may also cause nonsyndromic maculopathy. A series of 12 patients with nonsyndromic retinopathy due to novel CLN7/MFSD8 mutation combinations were investigated in this study. Methods: Affected patients and their family members were recruited in ophthalmic clinics at each center where they were examined by retinal imaging and detailed electrophysiology. Whole exome or genome next generation sequencing was performed on genomic DNA from at least one affected family member. Immunofluorescence confocal microscopy of murine retina cross-sections were used to localize the protein. Results: Compound heterozygous alleles were identified in six cases, one of which was always p.Glu336Gln. Such combinations resulted in isolated macular disease. Six further cases were homozygous for the variant p.Met454Thr, identified as a founder mutation of South Asian origin. Those patients had widespread generalized retinal disease, characterized by electroretinography as a rod-cone dystrophy with severe macular involvement. In addition, the photopic single flash electroretinograms demonstrated a reduced b- to a-wave amplitude ratio, suggesting dysfunction occurring after phototransduction. Immunohistology identified MFSD8 in the outer plexiform layer of the retina, a site rich in photoreceptor synapses. Conclusions: This study highlights a hierarchy of MFSD8 variant severity, predicting three consequences of mutation: (1) nonsyndromic localized maculopathy, (2) nonsyndromic widespread retinopathy, or (3) syndromic neurological disease. The data also shed light on the underlying pathogenesis by implicating the photoreceptor synaptic terminals as the major site of retinal disease

Testate amoeba response to acid deposition in a Scottish peatland

Peatlands around the world are exposed to anthropogenic or volcanogenic sulphur pollution. Impacts on peatland microbial communities have been inferred from changes in gas flux but have rarely been directly studied. In this study, the impacts of sulphuric acid deposition on peatland testate amoebae were investigated by analysis of experimental plots on a Scottish peatland almost 7 years after acid treatment. Results showed reduced concentration of live amoebae and changes in community structure which remained significant even when differences in pH were accounted for. Several possible explanations for the impacts can be proposed including taphonomic processes and changes in plant communities. Previous studies have inferred a shift from methanogenic archaea to sulphate-reducing bacteria in sulphate-treated peats; it is possible that the impacts detected here might relate to this change, perhaps through testate amoeba predation on methanotrophs

Where did all the nitrogen go? Fate of nitrogen inputs to large watersheds in the northeastern U.S.A.

To assess the fate of the large amounts of nitrogen (N) brought into the environment by human activities, we constructed N budgets for sixteen large watersheds (475 to 70,189 km 2) in the northeastern U.S.A. These watersheds are mainly forested (48-87%), but vary widely with respect to land use and population density. We combined published data and empirical and process models to set up a complete N budget for these sixteen watersheds. Atmospheric deposition, fertilizer application, net feed and food inputs, biological fixation, river discharge, wood accumulation and export, changes in soil N, and denitrification losses in the landscape and in rivers were considered for the period 1988 to 1992. For the whole area, on average 3420 kg of N is imported annually per km 2 of land. Atmospheric N deposition, N 2 fixation by plants, and N imported in commercial products (fertilizers, food and feed) contributed to the input in roughly equal contributions. We quantified the fate of these inputs by independent estimates of storage and loss terms, except for denitrification from land, which was estimated from the difference between all inputs and all other storage and loss terms. Of the total storage and losses in the watersheds, about half of the N is lost in gaseous form (51%, largely by denitrification). Additional N is lost in riverine export (20%), in food exports (6%), and in wood exports (5%). Change in storage of N in the watersheds in soil organic matter (9%) and wood (9%) accounts for the remainder of the sinks. The presence of appreciable changes in total N storage on land, which we probably under-rather than overestimated, shows that the N budget is not in steady state, so that drainage and denitrification exports of N may well increase further in the future.SCOPUS: ar.jinfo:eu-repo/semantics/publishe