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.     

Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes.

Type 2 diabetes is characterized by decreased rates of insulin-stimulated glucose uptake and utilization, reduced hexokinase II mRNA and enzyme production, and low basal levels of glucose 6-phosphate in insulin-sensitive skeletal muscle and adipose tissues. Hexokinase II is primarily expressed in muscle and adipose tissues where it catalyzes the phosphorylation of glucose to glucose 6-phosphate, a possible rate-limiting step for glucose disposal. To investigate the role of hexokinase II in insulin action and in glucose homeostasis as well as in mouse development, we generated a hexokinase II knock-out mouse. Mice homozygous for hexokinase II deficiency (HKII(-/-)) died at approximately 7.5 days post-fertilization, indicating that hexokinase II is vital for mouse embryogenesis after implantation and before organogenesis. HKII(+/-) mice were viable, fertile, and grew normally. Surprisingly, even though HKII(+/-) mice had significantly reduced (by 50%) hexokinase II mRNA and activity levels in skeletal muscle, heart, and adipose tissue, they did not exhibit impaired insulin action or glucose tolerance even when challenged with a high-fat diet.     

Material properties of films from enzymatically tailored arabinoxylans

Rye arabinoxylan, with an initial arabinose to xylose (Ara/Xyl) ratio of 0.50, was enzymatically modified with alpha-L-arabinofuranosidase. Different enzyme dosages were used to prepare arabinoxylan samples with a gradient of arabinose content varying from Ara/Xyl ratio 0.50 to 0.20. The degree of polymerization of the arabinoxylans was not affected by the enzymatic treatment, as detected with SEC-MALLS. Arabinoxylan samples with an Ara/Xyl ratio of 0.30 and below agglomerated in a water solution as seen by changes in light scattering. All samples, however, formed cohesive films upon drying, without addition of external plasticizers. The film from untreated arabinoxylan was completely amorphous; whereas films of the enzyme-treated arabinoxylans were semicrystalline with an increasing degree of crystallinity with decreasing arabinose content as determined by WAXS. Oxygen permeability measurements of the films showed that decreased arabinose content also resulted in lower oxygen permeability of the films. All films were strong and relatively stiff, but showed variations in strain at break. The moderately debranched film with an Ara/Xyl ratio of 0.37 had highest strain at break among all the films tested, yet was stiff and strong. This material also exhibited yielding and had stress/strain behavior similar to synthetic semicrystalline polymers, with a tendency to strain-induced crystallization. Such a combination of mechanical properties combined with oxygen barrier properties is very attractive for packaging applications.     

High cell density media for <Emphasis Type="Italic">Escherichia coli</Emphasis> are generally designed for aerobic cultivations – consequences for large-scale bioprocesses and shake flask cultures

Background  

For the cultivation of Escherichia coli in bioreactors trace element solutions are generally designed for optimal growth under aerobic conditions. They do normally not contain selenium and nickel. Molybdenum is only contained in few of them. These elements are part of the formate hydrogen lyase (FHL) complex which is induced under anaerobic conditions. As it is generally known that oxygen limitation appears in shake flask cultures and locally in large-scale bioreactors, function of the FHL complex may influence the process behaviour. Formate has been described to accumulate in large-scale cultures and may have toxic effects on E. coli.     

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.     

Genetic structure of the northwestern Russian wolf populations and gene flow between Russia and Finland

We examined the genetic diversity and structure of wolf populations in northwestern Russia. Populations in Republic of Karelia and Arkhangelsk Oblast were sampled during 1995–2000, and 43 individuals were genotyped with 10 microsatellite markers. Moreover, 118 previously genotyped wolves from the neighbouring Finnish population were used as a reference population. A relatively large amount of genetic variation was found in the Russian populations, and the Karelian wolf population tended to be slightly more polymorphic than the Arkhangelsk population. We found significant inbreeding (F = 0.094) in the Karelian, but not in the Arkhangelsk population. The effective size estimates of the Karelian wolf population based on the approximate Bayesian computation and linkage disequilibrium methods were 39.9 and 46.7 individuals, respectively. AMOVA-analysis and exact test of population differentiation suggested clear differentiation between the Karelian, Arkhangelsk and Finnish wolf populations. Indirect estimates of gene flow based on the level of population differentiation (ϕ _ST  = 0.152) and frequency of private alleles (0.029) both suggested a low level of gene flow between the populations (Nm = 1.4 and Nm = 3.7, respectively). Assignment analysis of Karelian and Finnish populations suggested an even lower number of recent migrants (less than 0.03) between populations, with a larger amount of migration from Finland to Karelia than vice versa. Our findings emphasise the role of physical obstacles and territorial behaviour in creating barriers to gene flow between populations in relatively limited geographical areas, even in large-bodied mammalian species with long-distance dispersal capabilities and an apparently continuous population structure.