Cardiac Manifestations During a Coxsackie B5 Epidemic

During a widespread Coxsackie B5 epidemic which occurred in Finland in the autumn of 1965 18 patients with acute myopericarditis were admitted to Kuopio Central Hospital (530 beds, representing a hospital district with 270,000 inhabitants) within a period of three months.The mean age of these patients was 28 years. Twelve were males and six were females.In 12 cases Coxsackie B5 virus and in one case Coxsackie A9 virus were isolated from the faeces. A significant increase in neutralizing antibodies or high antibody titres (≥1:128) were noted in 16 cases against Coxsackie B5 and in one case against Coxsackie A9. In two cases the cause of the myopericarditis remained obscure.All the patients had fever. Six showed all classical criteria of pericarditis: chest pain, pericardial rub, E.C.G. changes, and radiologically observable enlargement of the heart. As regards the various criteria, E.C.G. changes were found in all cases. Signs of cardiac tamponade were observed in one patient. Five, in addition, showed aseptic meningitis.All the patients recovered. Twelve were re-examined at an average of seven months after discharge from hospital. All were symptom-free except one, who still showed E.C.G. changes.     

Wnt signaling in kidney development and disease

The Wnt gene family, which encodes secreted growth and differentiation factors, has been implicated in kidney organogenesis. The Wnts control both ureteric bud development and signaling, but they also serve as inductive factors to regulate nephrogenesis in the mesenchcymal cells. Several of the Wnt genes are expressed in the developing kidney, and gene knock-out studies have revealed specific developmental functions for these. Consistent with this, changes in Wnt ligands and pathway components are associated with many kidney diseases, including kidney cancers, renal fibrosis, cystic kidney diseases, acute renal failure, diabetic nephropathy and ischaemic injury. It is these associations of the Wnt signaling system with kidney development and kidney diseases that form to topic of this review.Key words: Wnt signaling, tubule induction, ureter development, kidney diseases, kidney cancer     

Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes

Membrane type 1 matrix metalloproteinase (MT1-MMP, MMP14) is an efficient extracellular matrix (ECM) degrading enzyme that plays important roles in tissue homeostasis and cell invasion. Like a number of type I membrane proteins, MT1-MMP can be internalized from the cell surface through early and recycling endosomes to late endosomes, and recycled to the plasma membrane. Late endosomes participate in the biogenesis of small (30-100 nm) vesicles, exosomes, which redirect plasma membrane proteins for extracellular secretion. We hypothesized that some of the endosomal MT1-MMP could be directed to exosomes for extracellular release. Using cultured human fibrosarcoma (HT-1080) and melanoma (G361) cells we provide evidence that both the full-length 60 kDa and the proteolytically processed 43 kDa forms of MT1-MMP are secreted in exosomes. The isolated exosomes were identified by their vesicular structure in electron microscopy and by exosomal marker proteins CD9 and tumor susceptibility gene (TSG101). Furthermore, exosomes contained beta1-integrin (CD29). The exosomes were able to activate pro-MMP-2 and degrade type 1 collagen and gelatin, suggesting that the exosomal MT1-MMP was functionally active. The targeting of MT1-MMP in exosomes represents a novel mechanism for cancer cells to secrete membrane type metalloproteolytic activity into the extracellular space.     

Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor

Background  

Nuclear localization of proteolytically formed intracellular fragment of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and nuclear localization of ErbB4 receptor has been described in human breast cancer. Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic cascade leading to ErbB4 intracellular domain formation. Interactions between matrix metalloproteases and heparan sulfate have been described, but the effect of cell surface heparan sulfate on TACE activity has not been previously described.     

Phenotypic rescue of a Drosophila model of mitochondrial ANT1 disease

A point mutation in the Drosophila gene that codes for the major adult isoform of adenine nuclear translocase (ANT) represents a model for human diseases that are associated with ANT insufficiency [stress-sensitive B¹ (sesB¹)]. We characterized the organismal, bioenergetic and molecular phenotype of sesB¹ flies then tested strategies to compensate the mutant phenotype. In addition to developmental delay and mechanical-stress-induced seizures, sesB¹ flies have an impaired response to sound, defective male courtship, female sterility and curtailed lifespan. These phenotypes, excluding the latter two, are shared with the mitoribosomal protein S12 mutant, tko^25t. Mitochondria from sesB¹ adults showed a decreased respiratory control ratio and downregulation of cytochrome oxidase. sesB¹ adults exhibited ATP depletion, lactate accumulation and changes in gene expression that were consistent with a metabolic shift towards glycolysis, characterized by activation of lactate dehydrogenase and anaplerotic pathways. Females also showed downregulation of many genes that are required for oogenesis, and their eggs, although fertilized, failed to develop to the larval stages. The sesB¹ phenotypes of developmental delay and mechanical-stress-induced seizures were alleviated by an altered mitochondrial DNA background. Female sterility was substantially rescued by somatic expression of alternative oxidase (AOX) from the sea squirt Ciona intestinalis, whereas AOX did not alleviate developmental delay. Our findings illustrate the potential of different therapeutic strategies for ANT-linked diseases, based on alleviating metabolic stress.KEY WORDS: Adenine nucleotide translocase, Mitochondrial disease, Mitochondrial biogenesis, Alternative oxidase     

Human Brain Reacts to Transcranial Extraocular Light

Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain.     

Adenylyl Cyclases: mRNA and Characteristics of Enzyme Activity in Three Areas of Brain

Abstract: Arachidonic acid and oleoylacetylglycerol enhance depolarization-evoked glutamate release from hippocampal mossy fiber nerve endings. It was proposed this is a Ca²⁺-dependent effect and that protein kinase C is involved. Here we report that arachidonic acid and oleoylacetylglycerol synergistically potentiate the glutamate release induced by the Ca²⁺ ionophore ionomycin. The Ca²⁺ dependence of this effect was established, as removal of Ca²⁺ eliminated evoked release and the lipid-dependent potentiation. Also, Ca²⁺ channel blockers attenuated ionomycin- and KCI-evoked exocytosis, as well as the facilitating effects of the lipid mediators. Although facilitation required Ca²⁺, it may not involve an enhancement of evoked Ca²⁺ accumulation, because ionomycin-dependent glutamate release was potentiated under conditions that did not increase ionomycin-induced Ca²⁺ accumulation. Also, the facilitation may not depend on inhibition of K⁺ efflux, because enhanced release was observed in the presence of increasing concentrations of 4-aminopyridine and diazoxide did not reduce the lipid-dependent potentiation of exocytosis. In contrast, disruption of cytoskeleton organization with cytochalasin D occluded the lipid-dependent facilitations of both KCI- and ionomycin-evoked glutamate release. In addition, arachidonic acid plus glutamatergic or cholinergic agonists enhanced glutamate release, whereas a role for protein kinase C in the potentiation of exocytosis was substantiated using kinase inhibitors. It appears that the lipid-dependent facilitation of glutamate release from mossy fiber nerve endings requires Ca²⁺ and involves multiple presynaptic effects, some of which depend on protein kinase C.     

Population structure,life cycle,and trophic niche of the glacial relict amphipod,Gammaracanthus lacustris,in a large boreal lake

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Brain development and predation: plastic responses depend on evolutionary history

Although the brain is known to be a very plastic organ, the effects of common ecological interactions like predation or competition on brain development have remained largely unexplored. We reared nine-spined sticklebacks (Pungitius pungitius) from two coastal marine (predation-adapted) and two isolated pond (competition-adapted) populations in a factorial experiment, manipulating perceived predatory risk and food supply to see (i) if the treatments affected brain development and (ii) if there was population differentiation in the response to treatments. We detected differences in plasticity of the bulbus olfactorius (chemosensory centre) between habitats: marine fish were not plastic, whereas pond fish had larger bulbi olfactorii in the presence of perceived predation. Marine fish had larger bulbus olfactorius overall. Irrespective of population origin, the hypothalamus was smaller in the presence of perceived predatory risk. Our results demonstrate that perceived predation risk can influence brain development, and that the effect of an environmental factor on brain development may depend on the evolutionary history of a given population in respect to this environmental factor.