Aberrant Mitochondria in a Bethlem Myopathy Patient with a Homozygous Amino Acid Substitution That Destabilizes the Collagen VI α2(VI) Chain

Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD) sit at opposite ends of a clinical spectrum caused by mutations in the extracellular matrix protein collagen VI. Bethlem myopathy is relatively mild, and patients remain ambulant in adulthood while many UCMD patients lose ambulation by their teenage years and require respiratory interventions. Dominant and recessive mutations are found across the entire clinical spectrum; however, recessive Bethlem myopathy is rare, and our understanding of the molecular pathology is limited. We studied a patient with Bethlem myopathy. Electron microscopy of his muscle biopsy revealed abnormal mitochondria. We identified a homozygous COL6A2 p.D871N amino acid substitution in the C-terminal C2 A-domain. Mutant α2(VI) chains are unable to associate with α1(VI) and α3(VI) and are degraded by the proteasomal pathway. Some collagen VI is assembled, albeit more slowly than normal, and is secreted. These molecules contain the minor α2(VI) C2a splice form that has an alternative C terminus that does include the mutation. Collagen VI tetramers containing the α2(VI) C2a chain do not assemble efficiently into microfibrils and there is a severe collagen VI deficiency in the extracellular matrix. We expressed wild-type and mutant α2(VI) C2 domains in mammalian cells and showed that while wild-type C2 domains are efficiently secreted, the mutant p.D871N domain is retained in the cell. These studies shed new light on the protein domains important for intracellular and extracellular collagen VI assembly and emphasize the importance of molecular investigations for families with collagen VI disorders to ensure accurate diagnosis and genetic counseling.     

Composition and distribution of zooplankton in the Laptev Sea and adjacent Nansen Basin during summer, 1993

Zooplankton composition and distribution were investigated on the Laptev Sea shelf, over the continental slope and in the adjacent deep Nansen Basin during the joint German-Russian expedition “Arctic 93” with RV Polarstern and Ivan Kireyev in August/September 1993. In the shelf area biomass decreased from west to east with the lowest values in the area influenced by the Lena river runoff. A gradual increase of biomass from the shallow to the deep area correlated with water depth. Total biomass ranged between 0.1 and 1.5 g m⁻² on the shelf and 4.7 and 7.9 g m⁻² in the adjacent Nansen Basin. On the shelf Calanus glacialis/finmarchicus dominated overall. The contribution of brackish-water taxa was low in the west, where high salinity and southward currents from the Arctic Basin supported a marine neritic community, but on the southern and eastern Laptev shelf, in the areas of freshwater influence, brackish-water taxa contributed up to 27% of the total biomass. On the slope and in deep areas a few large Arctic copepod species, Calanus glacialis, C. hyperboreus and Metridia longa, composed the bulk of biomass and determined the pattern of its vertical distribution. The export of Calanus species from the Nansen Basin onto the Laptev shelf appears to be of great importance for the shelf communities. In turn, the eastern outer shelf and slope area of the Laptev Sea are thought to have a pronounced effect on the deep basin, modifying the populations entering the central Arctic. Received: 25 March 1997 / Accepted: 18 July 1997     

Wood pellets,what else? Greenhouse gas parity times of European electricity from wood pellets produced in the south‐eastern United States using different softwood feedstocks

Several EU countries import wood pellets from the south‐eastern United States. The imported wood pellets are (co‐)fired in power plants with the aim of reducing overall greenhouse gas (GHG) emissions from electricity and meeting EU renewable energy targets. To assess whether GHG emissions are reduced and on what timescale, we construct the GHG balance of wood‐pellet electricity. This GHG balance consists of supply chain and combustion GHG emissions, carbon sequestration during biomass growth and avoided GHG emissions through replacing fossil electricity. We investigate wood pellets from four softwood feedstock types: small roundwood, commercial thinnings, harvest residues and mill residues. Per feedstock, the GHG balance of wood‐pellet electricity is compared against those of alternative scenarios. Alternative scenarios are combinations of alternative fates of the feedstock materials, such as in‐forest decomposition, or the production of paper or wood panels like oriented strand board (OSB). Alternative scenario composition depends on feedstock type and local demand for this feedstock. Results indicate that the GHG balance of wood‐pellet electricity equals that of alternative scenarios within 0–21 years (the GHG parity time), after which wood‐pellet electricity has sustained climate benefits. Parity times increase by a maximum of 12 years when varying key variables (emissions associated with paper and panels, soil carbon increase via feedstock decomposition, wood‐pellet electricity supply chain emissions) within maximum plausible ranges. Using commercial thinnings, harvest residues or mill residues as feedstock leads to the shortest GHG parity times (0–6 years) and fastest GHG benefits from wood‐pellet electricity. We find shorter GHG parity times than previous studies, for we use a novel approach that differentiates feedstocks and considers alternative scenarios based on (combinations of) alternative feedstock fates, rather than on alternative land uses. This novel approach is relevant for bioenergy derived from low‐value feedstocks.     

Application of LCA as a decision-making tool for waste management systems

Aim, Scope and Background  When materials are recycled they are made available for use for several future life cycles and can therefore replace virgin material more than just once. In order to analyse the optimal waste management system for a given material, the authors have analysed the material flows in a life cycle perspective. It is important to distinguish this approach for material flow analysis for a given material from life cycle analysis of products. A product life cycle analysis analyses the product system from cradle to grave, but uses some form of allocation in order to separate the life cycle of one product from another in cases where component materials are recycled. This paper does not address allocation of burdens between different product systems, but rather focuses on methodology for decision making for waste management systems where the optimal waste management system for a given material is analysed. The focus here is the flow of the given material from cradle (raw material extraction) to grave (the material, or its inherent energy, is no longer available for use). The limitation on the number of times materials can be recycled is set by either the recycling rate, or the technical properties of the recycled material. Main Features  This article describes a mathematical geometric progression approach that can be used to expand the system boundaries and allow for recycling a given number of times. Case studies for polyethylene and paperboard are used to illustrate the importance of including these aspects when part of the Goal and Scope for the LCA study is to identify which waste management treatment options are best for a given material. The results and discussion examine the different conclusions that can be reached about which waste management option is most environmentally beneficial when the higher burdens and benefits of recycling several times are taken into account. Results  In order to assess the complete picture of the burdens and benefits arising from recycling the system boundaries must be expanded to allow for recycling many times. A mathematical geometric progression approach manages to take into account the higher burdens and benefits arising from recycling several times. If one compares different waste management systems, e.g. energy recovery with recycling, without expanding the system to include the complete effects of material recycling one can reach a different conclusion about which waste management option is preferred. Conclusions  When the purpose of the study is to compare different waste management options, it is important that the system boundaries are expanded in order to include several recycling loops where this is a physical reality. The equations given in this article can be used to include these recycling loops. The error introduced by not expanding the system boundaries can be significant. This error can be large enough to change the conclusions of a comparative study, such that material recycling followed by incineration is a much better option than waste incineration directly. Recommendations and Outlook  When comparing waste management solutions, where material recycling is a feasible option, it is important to include the relevant number of recycling loops to ensure that the benefits of material recycling are not underestimated. The methodology presented in this article should be used in future comparative studies for strategic decision-making for waste management. The approach should not be used for LCAs for product systems without due care, as this could lead to double counting of the benefits of recycling (depending on the goal and scope of the analysis). For materials where the material cycle is more of a closed loop and one cannot truly say that recycled materials replace virgin materials, a more sophisticated approach will be required, taking into account the fact that recycled materials will only replace a certain proportion of virgin materials.     

Indeterminate laying and flexible clutch size in a capital breeder, the common eider

Clutch size control in capital breeders such as large waterfowl has been much debated. Some studies have concluded that clutch size in ducks is determined before the start of laying and does not change in response to egg additions or removals. The response, however, may depend on the timing of tests, and experiments may have been too late for females to alter the number of eggs. We here study clutch size responses to predation of first and second eggs in the common eider, using protein fingerprinting of egg albumen to verify that the same female continues laying in the nest after predation. Sixty of 79 females with early egg predation (one or both of the two first eggs) deserted the nest. Among the 19 females that stayed and continued laying, the mean number of eggs produced was 4.4, significantly higher than the 3.7 in non-predated nests. The staying females had similar egg size and clutch initiation date as females that deserted, and their body mass and clutch initiation date was similar to that of females whose clutches were not predated. Even capital-breeding common eiders may therefore be indeterminate layers, as many females in which early eggs are removed lay more eggs than others. A previous study has shown that they can reduce their laying if eggs are added. Our results add to increasing evidence that ducks have more flexible egg production than previously thought.     

Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. ¹²⁵I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism.