Mitochondrial intermembrane inclusion bodies: The common denominator between human mitochondrial myopathies and creatine depletion due to impairment of cellular energetics

Mitochondrial inclusion bodies are often described in skeletal muscle of patients suffering diseases termed mitochondrial myopathies. A major component of these structures was discovered as being creatine kinase. Similar creatine kinase enriched inclusion bodies in the mitochondria of creatine depleted adult rat cardiomyocytes have been demonstrated. Structurally similar inclusion bodies are observed in mitochondria of ischemic and creatine depleted rat skeletal muscle. This paper describes the various methods for inducing mitochondrial inclusion bodies in rodent skeletal muscle, and compares their effects on muscle metabolism to the metabolic defects of mitochondrial myopathy muscle. We fed rats with a creatine analogue guanidino propionic acid and checked their soled for mitochondrial inclusion bodies, with the electron microscope. The activity of creatine kinase was analysed by measuring creatine stimulated oxidative phosphorylation in soleus skinned fibres using an oxygen electrode . The guanidino propionic acid-rat soleus mitochondria displayed no creatine stimulation, whereas control soleus did, even though the GPA soled had a five fold increase in creatine kinase protein per mitochondrial protein. The significance of these results in light of their relevance to human mitochondrial myopathies and the importance of altered muscle metabolism in the formation of these crystalline structures are discussed. (Mol Cell Biochem 174: 283–289, 1997)     

Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion

The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p < 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p < 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.     

An increase in the abundance of anchovies and sardines in the north-western North Sea since 1995

Trawl data from Scottish research vessels dating from January 1925 show that catches of the warm water pelagic species, anchovy ( Engraulis encrasicholus ) and sardine ( Sardina pilchardus ), increased suddenly after 1995. Most were observed in the first quarter of each year, with 1998 and 2003 having the largest numbers, although few data are available for the last quarter. The authors believe that these long-term changes are related to rising sea temperatures although the exact causal mechanism is not clear.     

Cryo-EM Elucidation of the Structure of Bacteriophage P22 Virions after Genome Release

Genome ejection proteins are required to facilitate transport of bacteriophage P22 double-stranded DNA safely through membranes of Salmonella. The structures and locations of all proteins in the context of the mature virion are known, with the exception of three ejection proteins. Furthermore, the changes that occur to the proteins residing in the mature virion upon DNA release are not fully understood. We used cryogenic electron microscopy to obtain what is, to our knowledge, the first asymmetric reconstruction of mature bacteriophage P22 after double-stranded DNA has been extruded from the capsid—a state representative of one step during viral infection. Results of icosahedral and asymmetric reconstructions at estimated resolutions of 7.8 and 12.5 Å resolutions, respectively, are presented. The reconstruction shows tube-like protein density extending from the center of the tail assembly. The portal protein does not revert to the more contracted, procapsid state, but instead maintains an extended and splayed barrel structure. These structural details contribute to our understanding of the molecular mechanism of P22 phage infection and also set the foundation for future exploitation serving engineering purposes.     

Butterflies of European islands: the implications of the geography and ecology of rarity and endemicity for conservation

Depending on their faunal content islands can function as important ‘vehicles’ for conservation. In this study, we examine data on 440 butterfly species over 564 European islands in 10 island groups. To determine the status of the butterfly fauna, we have adopted two approaches, island-focused and species-focused, examined using principal components analysis and regression modelling. In the former, we relate species richness, rarity and endemicity to island geography (area, elevation, isolation and location in latitude and longitude); in the latter, species occurrence on islands is examined in relation to distribution, range, range boundaries, and altitudinal limits on the continent as well as species’ ecology (number of host plants) and morphology (wing expanse). Species on islands are also assessed for their status on the continental mainland, their distributional dynamics (extinctions, distribution changes) and conservation status (Red Data Book, European Habitat Directive, Species of European Conservation Concern and Bern Convention listing. Unexpectedly, we find that a large fraction of the European butterfly species is found on the islands (63.4%; 59% on small islands) comprising some 6.2% of the land area of Europe. Although species occurring on the islands tend, on the whole, to have lower conservation status and are not declining over Europe, 45 species are endemics restricted to the islands. Species richness shows only a weak locational pattern and is related as expected to isolation from the continental source and island area; but, both rarity and endemicity have distinctive geographical bias to southern Europe, on islands now under increasing pressure from climate change and increasingly intensive human exploitation. The vulnerability of species on islands is emphasised in the relationship of island occurrence (% occurrence and presence/absence of species on any island) with continental distributions. A large proportion of the variation (84%) is accounted by continental distribution, the southern range limit and lower altitudinal limit. Most species (69%) occur on very few islands (<5%). In view of ongoing species dynamics on islands, migrations and extinctions of species, island repositories of species depend in large part on conservation of butterflies at continental sources. The unique faunas and rare species on islands also depend on appropriate concern being given to the island faunas. Conservation of European islands is thus a two-way process, sustaining sources and conserving island refuges. Residuals from the regressions (islands with more or fewer species, rare and endemic species; species occurring more or less frequently than expected on islands) provide warning signals of regions and islands deserving immediate attention.     

Sedimentation in Boreal Lakes—The Role of Flocculation of Allochthonous Dissolved Organic Matter in the Water Column

We quantified sedimentation of organic carbon in 12 Swedish small boreal lakes (<0.48 km²), which ranged in dissolved organic carbon (DOC) from 4.4 to 21.4 mg C l⁻¹. Stable isotope analysis suggests that most of the settling organic matter is of allochthonous origin. Annual sedimentation of allochthonous matter per m² lake area was correlated to DOC concentration in the water (R ² = 0.41), and the relationship was improved when sedimentation data were normalized to water depth (R ² = 0.58). The net efflux of C as CO₂ from the water to the atmosphere was likewise correlated to DOC concentration (R ² = 0.52). The losses of organic carbon from the water column via mineralization to CO₂ and via sedimentation were approximately of equal importance throughout the year. Our results imply that DOC is a precursor of the settling matter, resulting in an important pathway in the carbon cycle of boreal lakes. Thus, flocculation of DOC of terrestrial origin and subsequent sedimentation could lead to carbon sequestration by burial in lake sediments.     

Infantile hypertrophic pyloric stenosis: evaluation of three positional candidate genes, <Emphasis Type="Italic">TRPC1</Emphasis>, <Emphasis Type="Italic">TRPC5</Emphasis> and <Emphasis Type="Italic">TRPC6</Emphasis>, by association analysis and re-sequencing

Infantile hypertrophic pyloric stenosis (IHPS) is the most common inherited form of gastrointestinal obstruction in infancy with a striking male preponderance. Infants present with vomiting due to gastric outlet obstruction caused by hypertrophy of the smooth muscle of the pylorus. Two loci specific to extended pedigrees displaying autosomal dominant inheritance have been identified. A genome scan identified loci on chromosomes 11q14–q22 and Xq23–q24 which are predicted to be responsible for a subset of smaller families with IHPS demonstrating non-Mendelian inheritance. The two linked chromosomal regions both harbour functional candidate genes which are members of the canonical transient receptor potential (TRPC) family of ion channels. Both TRPC5 (Xq23–q24) and TRPC6 (11q14–q22) have a potential role in smooth muscle control and hypertrophy. Here, we report suggestive evidence for a third locus on chromosome 3q12–q25 (Z _max = 2.7, p < 0.004), a region which harbours a third TRPC gene, TRPC1. Fine mapping of all three genes using a tagSNP approach and re-sequencing identified a SNP in the promoter region of TRPC6 and a missense variant in exon 4 of TRPC6 which may be putative causal variants.