Effect of Ascorbate on Coagulation and Fibrinolytic Factors in the Septic Microvasculature

Sepsis, a systemic inflammatory response to an infection, is a significant cause of morbidity and mortality worldwide. The microcirculation during sepsis fails, in part, due to microthrombosis and the resulting plugging of capillaries, precipitating organ failure. Intravenous injection of ascorbate has been shown to reduce capillary plugging, however the mechanism of this protective effect is unclear. We hypothesized that ascorbate-mediated destabilization of the microthrombi through promoting fibrinolysis could contribute to this protection. We showed that streptokinase, a pro-fibrinolytic agent, reduced the capillary plugging to a similar degree as ascorbate. This similarity provided the impetus for studying the effect of ascorbate on fibrinolysis. Sepsis increased the urokinase plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) mRNA expression in the skeletal muscle and liver in mice. No effect of ascorbate was observed on u-PA or t-PA expression levels. Sepsis also increased the plasminogen activator inhibitor 1 (PAI-1) mRNA and protein expression and activity in these tissues, but ascorbate did not affect these increases. The local PAI-1 release by both platelets and endothelial cells may play a critical role in microthrombus formation in capillaries. We observed that PAI-1 released by isolated endothelial cells was not affected by ascorbate. However, thrombin-induced PAI-1 release from platelets was inhibited by ascorbate pH-dependently. We have also discovered that the PAI-1 release from platelets was nitric oxide independent. It has been shown that PAI-1 has a protective role in sepsis, namely that PAI-1 knockout leads to increased bacterial content, increased neutrophil apoptosis and increased mortality. Therefore, the lack of effect of ascorbate on PAI-1 in the tissue may maintain PAI-1’s beneficial role in sepsis. Consistently, we observed that sepsis-induced increases in bacterial count, PAI-1 expression and myeloperoxidase content in various organs were not affected by ascorbate. Overall, the lack of effect of ascorbate indicates that the protection by ascorbate through reduced capillary plugging is not through a fibrinolytic mechanism. Other mechanisms such as platelet-endothelial cell adhesion and changes in red blood cell deformability in the capillaries should be explored as possible mechanisms of protection by ascorbate

Notes on the meteorology and mortality of the month of June, 1870.

Meteorological records recorded at the Observatory, Hobart Town. Also includes leafing, flowering, and fruiting times of a few standard plants in the Royal Societies gardens for the month of June, 1870.- The general character of the month was not propitious to life, and the deaths of adults, and particularly old people above 60 years old, were unusually large, while in children under 10 years of age, the deaths were remarkably few. Nevertheless, there was no prevailing sickness of an epidemic character

The mucin-degradation strategy of Ruminococcus gnavus:The importance of intramolecular trans-sialidases

We previously identified and characterized an intramolecular trans-sialidase (IT-sialidase) in the gut symbiont Ruminococcus gnavus ATCC 29149, which is associated to the ability of the strain to grow on mucins. In this work we have obtained and analyzed the draft genome sequence of another R. gnavus mucin-degrader, ATCC 35913, isolated from a healthy individual. Transcriptomics analyses of both ATCC 29149 and ATCC 35913 strains confirmed that the strategy utilized by R. gnavus for mucin-degradation is focused on the utilization of terminal mucin glycans. R. gnavus ATCC 35913 also encodes a predicted IT-sialidase and harbors a Nan cluster dedicated to sialic acid utilization. We showed that the Nan cluster was upregulated when the strains were grown in presence of mucin. In addition we demonstrated that both R. gnavus strains were able to grow on 2,7-anyhydro-Neu5Ac, the IT-sialidase transglycosylation product, as a sole carbon source. Taken together these data further support the hypothesis that IT-sialidase expressing gut microbes, provide commensal bacteria such as R. gnavus with a nutritional competitive advantage, by accessing and transforming a source of nutrient to their own benefit

The pan-genome of Lactobacillus reuteri strains originating from the pig gastrointestinal tract

Background Lactobacillus reuteri is a gut symbiont of a wide variety of vertebrate species that has diversified into distinct phylogenetic clades which are to a large degree host-specific. Previous work demonstrated host specificity in mice and begun to determine the mechanisms by which gut colonisation and host restriction is achieved. However, how L. reuteri strains colonise the gastrointestinal (GI) tract of pigs is unknown. Results To gain insight into the ecology of L. reuteri in the pig gut, the genome sequence of the porcine small intestinal isolate L. reuteri ATCC 53608 was completed and consisted of a chromosome of 1.94 Mbp and two plasmids of 138.5 kbp and 9.09 kbp, respectively. Furthermore, we generated draft genomes of four additional L. reuteri strains isolated from pig faeces or lower GI tract, lp167-67, pg-3b, 20-2 and 3c6, and subjected all five genomes to a comparative genomic analysis together with the previously completed genome of strain I5007. A phylogenetic analysis based on whole genomes showed that porcine L. reuteri strains fall into two distinct clades, as previously suggested by multi-locus sequence analysis. These six pig L. reuteri genomes contained a core set of 1364 orthologous gene clusters, as determined by OrthoMCL analysis, that contributed to a pan-genome totalling 3373 gene clusters. Genome comparisons of the six pig L. reuteri strains with 14 L. reuteri strains from other host origins gave a total pan-genome of 5225 gene clusters that included a core genome of 851 gene clusters but revealed that there were no pig-specific genes per se. However, genes specific for and conserved among strains of the two pig phylogenetic lineages were detected, some of which encoded cell surface proteins that could contribute to the diversification of the two lineages and their observed host specificity. Conclusions This study extends the phylogenetic analysis of L. reuteri strains at a genome-wide level, pointing to distinct evolutionary trajectories of porcine L. reuteri lineages, and providing new insights into the genomic events in L. reuteri that occurred during specialisation to their hosts. The occurrence of two distinct pig-derived clades may reflect differences in host genotype, environmental factors such as dietary components or to evolution from ancestral strains of human and rodent origin following contact with pig populations

Cyanobacteria and Biosequestration: The Effects of High CO2 Levels on Calcifying Strains of Synechococcus

Increased carbon dioxide levels in the atmosphere and its influence on climate change is a growing concern in the scientific, political, and social communities. Methods of mitigation are being tested to explore carbon capture and storage through the biosynthesis of stable carbon-containing compounds using different strains of calcifying cyanobacteria. By utilizing marine genera, the cyanobacteria could potentially be grown in brine waste waters, conserving valuable fresh water resources. In this experiment, two strains of Synechococcus were cultured in flasks with varying levels of CO2: air, 5% CO2, and 15% CO2. Growth of each culture was monitored by measuring optical density and pH level, as calcification requires an alkaline environment. Morphological characteristics of each culture were analyzed through light microscopy and scanning electron microscopy to compare differences in cell surface and association. Preliminary results have shown inconsistent morphology and growth. Cultures started from previous experiments lacked duplication of observed filamentous morphology, but exhibited better growth in high CO2 levels. The incubation of cultures in media with varying levels of calcium chloride will be used to analyze and compare the sequestration of carbon through calcium carbonate production. Analysis of the chemical composition of precipitates in the media and the S-layer of cells will verify the presence of calcium carbonate. Methods include the use of SEM-EDX (energy-dispersive X-ray spectroscopy) and polarized light microscopy. If experimental outcomes verify efficient production of calcium carbonate from sources of high CO2, these cyanobacteria may be viable systems for capturing carbon

E.S. Hall Medical & Vital Statistics 1856 Index: Royal Society Collection

Edward Swarbreck Hall (1805-1881) was a medical practitioner who arrived in Hobart in 1832 and held various government appointments as district surgeon in Brighton, Bothwell, Westbury and Midland towns. In 1853 he was appointed house surgeon to the Hobart Hospital from which he resigned in 1855 but held several other official appointments. He campaigned for various health reforms. He was also a member of the Royal Society of Tasmania to which he gave addresses and presented copies of statistics he had prepared. Held in the Library - Medical and vital statistics 1856 Report and tables, with returns, prepared for the Royal Society of Tasmania. (49 pp, plus 6 pp. tables) RS.5

Calcium-Mediated Abiotic Stress Signaling in Roots.

Roots are subjected to a range of abiotic stresses as they forage for water and nutrients. Cytosolic free calcium is a common second messenger in the signaling of abiotic stress. In addition, roots take up calcium both as a nutrient and to stimulate exocytosis in growth. For calcium to fulfill its multiple roles must require strict spatio-temporal regulation of its uptake and efflux across the plasma membrane, its buffering in the cytosol and its sequestration or release from internal stores. This prompts the question of how specificity of signaling output can be achieved against the background of calcium's other uses. Threats to agriculture such as salinity, water availability and hypoxia are signaled through calcium. Nutrient deficiency is also emerging as a stress that is signaled through cytosolic free calcium, with progress in potassium, nitrate and boron deficiency signaling now being made. Heavy metals have the capacity to trigger or modulate root calcium signaling depending on their dose and their capacity to catalyze production of hydroxyl radicals. Mechanical stress and cold stress can both trigger an increase in root cytosolic free calcium, with the possibility of membrane deformation playing a part in initiating the calcium signal. This review addresses progress in identifying the calcium transporting proteins (particularly channels such as annexins and cyclic nucleotide-gated channels) that effect stress-induced calcium increases in roots and explores links to reactive oxygen species, lipid signaling, and the unfolded protein response.Funding for this work was from the BBSRC (BB/K009869/1 and Doctoral Training Programme) and the University of Cambridge Broodbank Trust.This is the final version of the article. It first appeared from Frontiers at http://dx.doi.org/10.3389/fpls.2016.01296

Summary of weather and health in 1865

The weather generally in 1865 was of the most favorable character. Atmospheric mean pressure for the year was 29-848, which is only + 040 above the 20 years' mean of the adopted standard. February, May, Septennber, December, had means below the average, but all the other months were above it. The greatest pressure noted was 30 566 on the 8th August,and the lowest was 28 885 on the 14th May, the extreme range for the year, therefore, being 1 681 inches

Letter from Edward Swarbreck Hall, Medical practitioner, Bothwell to John Clark of Cluny regarding Mrs Clark's accouchement (1839).

Letter from Edward Swarbreck Hall, Medical practitioner, Bothwell to John Clark of Cluny regarding Mrs Clark's accouchement (dated 30th October 1839). Edward Swarbreck Hall (1805-1881) was a medical practitioner who arrived in Hobart in 1832 and held various government appointments as district surgeon in Brighton, Bothwell, Westbury and Midland towns. In 1853 he was appointed house surgeon to the Hobart Hospital from which he resigned in 1855 but held several other official appointments. He campaigned for various health reforms. He was also a member of the Royal Society of Tasmania. RS8/B Correspondence - 23 - Edward Swarbreck Hall 1839-184

On a probably new species of Lamprey found in Tasmania

The singular fish I have the honor to lay before this monthly meeting of the Society, was transmitted to me by the Rev. E. C. Marum, of Jerusalem, with the request that I would present it to the Museum, if worthy of acceptance. It was caught by Mr. John Ibbott, near Stockdale, six miles south of Jerusalem, whilst netting for rock-roach, in the Coal River. This part of the river is entirely fresh water, and far above tidal influence. When removed from the net it was living, and firmly adhering by its sucker-like mouth to a rock-roach fish. "When placed in a dish of water," says the Rev. Mr. Marum, "he at once adjusted his pouch charmingly, reminding me of the days when I used a set of bladders in learning to swim; he seemed to sink and rise then as a boat or ship does when at anchor as the waves or ripples move them.