Mitochondria to the rescue

A new study using a mouse model of lung diseases is the first demonstration in vivo that bone marrow–derived stromal cells can repair tissue injury through the transfer of mitochondria (pages 759-765). This suggests that rescue of injured cells through mitochondrial transfer may be an important process in many diseases.     

UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play different roles in the development of Drosophila melanogaster

In both humans and Drosophila melanogaster, UDP-galactose 4'-epimerase (GALE) catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP-glucose (UDP-glc) in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE) efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU) efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans.     

Unspecific labeling of pancreatic islets by antisera against fibroblast growth factors and their receptors.

Six distinct fibroblast growth factors (FGFs) have been detected in pancreatic islets by immunohistochemistry (IHC) using commercially available antisera. We show here that these antisera are useful for Western blotting but that only two are suited for IHC. By Western blotting, these antisera detect recombinant FGFs. Detection can be eliminated by preabsorption with immunizing peptide but not with irrelevant peptide. By IHC we find specific labeling of islets with anti-FGF1 and anti-FGF2 antisera. Labeling can be abolished by preabsorption with the immunizing peptides. In contrast, prominent staining of islets by anti-FGF4, -FGF5, -FGF7, and -FGF10 antisera is unspecific because the staining cannot be competed by preabsorption with the immunizing peptides.     

Mechanism of bovine liver glutamate dehydrogenase self-assembly: III. Characterization of the association-dissociation stoichiometry with quasi-elastic light scattering

The homodyne light-scattering autocorrelation function originating in translational diffusion has been simulated for a polymerization model proposed for a number of self-associating systems: the sequential addition of identical monomer units to a growing aggregate, with identical equilibrium constants for each step. Both spherical and rigid rod structures have been considered. When applied to quasi-elastic light scattering data on glutamate dehydrogenase self-assembly, the simulation results indicate the formation of elongated polymers having equivalent and identical association sites. The weak response of translational diffusion coefficients to solution non-ideality leads to a valuable test of the unique equilibrium constant assumption. On the other hand, it is shown that successful exploitation of quasi-elastic light scattering data on aggregating systems of this type relies heavily on independent information.     

A New PCR-Based Approach Indicates the Range of Clonorchis sinensis Now Extends to Central Thailand

Differentiation of the fish-borne trematodes belonging to the Opisthorchiidae, Heterophyidae and Lecithodendriidae is important from a clinical and epidemiological perspective, yet it is impossible to do using conventional coprological techniques, as the eggs are morphologically similar. Epidemiological investigation therefore currently relies on morphological examination of adult worms following expulsion chemotherapy. A PCR test capable of amplifying a segment of the internal transcribed spacer region of ribosomal DNA for the opisthorchiid and heterophyid flukes eggs taken directly from faeces was developed and evaluated in a rural community in central Thailand. The lowest quantity of DNA that could be amplified from individual adults of Opisthorchis viverrini, Clonorchis sinensis and Haplorchis taichui was estimated at 0.6 pg, 0.8 pg and 3 pg, respectively. The PCR was capable of detecting mixed infection with the aforementioned species of flukes under experimental conditions. A total of 11.6% of individuals in rural communities in Sanamchaikaet district, central Thailand, were positive for ‘Opisthorchis-like’ eggs in their faeces using conventional parasitological detection techniques. In comparison to microscopy, the PCR yielded a sensitivity and specificity of 71.0% and 76.7%, respectively. Analysis of the microscopy-positive PCR products revealed 64% and 23% of individuals to be infected with O. viverrini and C. sinensis, respectively. The remaining 13% (three individuals) were identified as eggs of Didymozoidae, presumably being passed mechanically in the faeces following the ingestion of infected fishes. An immediate finding of this study is the identification and first report of a C. sinensis–endemic community in central Thailand. This extends the known range of this liver fluke in Southeast Asia. The PCR developed herein provides an important tool for the specific identification of liver and intestinal fluke species for future epidemiological surveys.     

Selection of the conodont Idiognathodus simulator (Ellison) as the event marker for the base of the global Gzhelian Stage (Upper Pennsylvanian, Carboniferous)

Studies carried out for more than 10 years by the Task Group to establish GSSPs at the base of the Moscovian–Kasimovian and Kasimovian–Gzhelian boundaries have resulted in the proposal that the level at which the conodont species Idiognathodus simulator (Ellison, 1941) first appears be selected to mark the base of the Gzhelian Stage. This expands this eastern European chronostratigraphic unit to a global scale.I. simulator (sensu Barrick et al., 2008) has been identified so far in Midcontinent and eastern North America, the Moscow and Donets basins and southern Urals of eastern Europe, and in south-central China. Correlation of this level based on this species and other conodont species can be reinforced in some areas by ammonoid and fusulinid data.     

Postmortem diagnosis and toxicological validation of illicit substance use.

The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and nine opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine and 33% opioid cases. Next-of-kin interviews identified almost twice as many cocaine and cannabis cases as Medical Examiner (ME) case histories, and were crucial in establishing a detailed lifetime substance use history. Toxicology identified 91% cocaine, 68% cannabis, 80% phencyclidine and 100% opioid cases, with hair testing increasing detection for all drug classes. A cocaine or cannabis use history was corroborated by general toxicology with 50% and 32% sensitivity, respectively, and with 82% and 64% sensitivity by hair testing. Hair testing corroborated a positive general toxicology for cocaine and cannabis with 91% and 100% sensitivity, respectively. Case history corroborated hair toxicology with 38% sensitivity for cocaine and 79% sensitivity for cannabis, suggesting that both case history and general toxicology underestimated cocaine use. Identifying ante-mortem substance use in human postmortem cases are key considerations in case diagnosis and for characterization of disorder-specific changes in neurobiology. The sensitivity and specificity of substance use assessments increased when ME case history was supplemented with structured next-of-kin interviews to establish a detailed lifetime substance use history, while comprehensive toxicology, and hair testing in particular, increased detection of recent illicit substance use.