S-Adenosyl-L-Methionine protects the probiotic yest, \u3cem\u3eSaccharomyces boulardii\u3c/em\u3e, from acid-induced cell death

Background Saccharomyces boulardii is a probiotic yeast routinely used to prevent and to treat gastrointestinal disorders, including the antibiotic-associated diarrhea caused by Clostridium difficile infections. However, only 1-3% of the yeast administered orally is recovered alive in the feces suggesting that this yeast is unable to survive the acidic environment of the gastrointestinal tract. Results We provide evidence that suggests that S. boulardii undergoes programmed cell death (PCD) in acidic environments, which is accompanied by the generation of reactive oxygen species and the appearance of caspase-like activity. To better understand the mechanism of cell death at the molecular level, we generated microarray gene expression profiles of S. boulardii cells cultured in an acidic environment. Significantly, functional annotation revealed that the up-regulated genes were significantly over-represented in cell death pathways Finally, we show that S-adenosyl-L-methionine (AdoMet), a commercially available, FDA-approved dietary supplement, enhances the viability of S. boulardii in acidic environments, most likely by preventing programmed cell death. Conclusions In toto, given the observation that many of the proven health benefits of S. boulardii are dependent on cell viability, our data suggests that taking S. boulardii and AdoMet together may be a more effective treatment for gastrointestinal disorders than taking the probiotic yeast alone

Neutron imaging and tomography with MCPs

A neutron imaging detector based on neutron-sensitive microchannel plates (MCPs) was constructed and tested at beamlines of thermal and cold neutrons. The MCPs are made of a glass mixture containing B-10 and natural Gd, which makes the bulk of the MCP an efficient neutron converter. Contrary to the neutron sensitive scintillator screens normally used in neutron imaging, spatial resolution is not traded off with detection efficiency. While the best neutron imaging scintillators have a detection efficiency around a percent, a detection efficiency of around 50% for thermal neutrons and 70% for cold neutrons has been demonstrated with these MCPs earlier. Our tests show a performance similar to conventional neutron imaging detectors, apart from the orders of magnitude better sensitivity. We demonstrate a spatial resolution better than 150 um. The sensitivity of this detector allows fast tomography and neutron video recording, and will make smaller reactor sites and even portable sources suitable for neutron imaging.Comment: Submitted to the proceedings of the 19th International Workshop on Radiation Imaging Detectors (iWoRiD) 2-6 July 2017, Krakow, Polan

William Pitt and the origins of the loyalist association movement of 1792

© 1996 Cambridge University Press.This article presents new and conclusive evidence to resolve the long-running controversy over whether the loyalist association movement of 1792 was spontaneous or was crafted by government. It shows that Pitt and his colleagues did not know in advance of John Reeves's proposals for the Crown and Anchor association before they were published on 23 November and it suggests who Reeves's original collaborators probably were. It then goes on to show how Pitt and his cousin, Lord Grenville, confronted with many demands and proposals for associations at this time, quickly seized upon the Reeves project as the most adaptable to their own ends and produced a new draft, redefining his proposals in the directions they were prepared to see such a movement take. This they induced Reeves to publish as a second declaration on 26 November and they went on to promote as the example and inspiration for a wider association movement

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Disaster Decision Making: Hurricanes Katrina and Gustav in New Orleans

The goal of this project was to set standard criteria for evaluating the execution of a disaster response at the local, State, and Federal Government levels. This evaluation, which was based on the disaster responses to Hurricanes Katrina and Gustav, focused on improvements in decision making. This project's procedure consisted of developing a model of decisions made and analyzing them. It was determined that there is a need for competent leadership, conducting rehearsals, and more initiative at all government levels

Characterization of New Spt3 and TATA-Binding Protein Mutants of Saccharomyces cerevisiae: Spt3–TBP Allele-Specific Interactions and Bypass of Spt8

The Spt-Ada-Gcn5-acetyltransferase (SAGA) complex of Saccharomyces cerevisiae is a multifunctional coactivator complex that has been shown to regulate transcription by distinct mechanisms. Previous results have shown that the Spt3 and Spt8 components of SAGA regulate initiation of transcription of particular genes by controlling the level of TATA-binding protein (TBP/Spt15) associated with the TATA box. While biochemical evidence exists for direct Spt8–TBP interactions, similar evidence for Spt3–TBP interactions has been lacking. To learn more about Spt3–TBP interactions in vivo, we have isolated a new class of spt3 mutations that cause a dominant-negative phenotype when overexpressed. These mutations all cluster within a conserved region of Spt3. The isolation of extragenic suppressors of one of these spt3 mutations has identified two new spt15 mutations that show allele-specific interactions with spt3 mutations with respect to transcription and the recruitment of TBP to particular promoters. In addition, these new spt15 mutations partially bypass an spt8 null mutation. Finally, we have examined the level of SAGA–TBP physical interaction in these mutants. While most spt3, spt8, and spt15 mutations do not alter SAGA–TBP interactions, one spt3 mutation, spt3-401, causes a greatly increased level of SAGA–TBP physical association. These results, taken together, suggest that a direct Spt3–TBP interaction is required for normal TBP levels at Spt3-dependent promoters in vivo

Qualitative and quantitative measurement of the anterior and posterior meniscal root attachments of the New Zealand white rabbit

Background: The purpose of this study was to quantify the meniscal root anatomy of the New Zealand white rabbit to better understand this animal model for future in vitro and in vivo joint degeneration studies. Methods: Ten non-paired fresh frozen New Zealand white rabbit knee stifle joints were carefully disarticulated for this study. Measurements were made for all bony landmarks and ligamentous structure attachment sites on the tibial plateau. The following soft tissue structures were consistently identified in the rabbit stifle joint: the anterior root attachment of the lateral meniscus, the anterior root attachment of the medial meniscus, the anterior cruciate ligament, the posterior root attachment of the medial meniscus, the ligament of Wrisberg, the posterior cruciate ligament, and the posterior meniscotibial ligament. The following bony landmarks were consistently identified: the extensor digitorum longus groove, the medial tibial eminence, the center of the tibial tuberosity, and the lateral tibial eminence. Results: The center of the anterior cruciate ligament and the medial tibial eminence apex were found to be 3.4 ± 0.3 mm (2.9–3.6) and 6.1 ± 0.6 mm (5.1–7.0) respectively from the center of the medical anterior root attachment. The center of the anterior cruciate ligament and the lateral tibial eminence apex were found to be 2.1 ± 0.5 mm (1.2–2.7) and 7.0 ± 0.6 mm (6.4–8.2) respectively from the center of the lateral anterior root attachment. The center of the posterior cruciate ligament and the medial tibial eminence apex were found to be 2.0 ± 0.7 mm (0.5–2.6) and 1.8 ± 0.4 mm (1.2–2.4) respectively from the center of the medial posterior root attachment. Conclusions: This study augments our understanding of the comparative anatomy of the rabbit stifle joint. This information will be useful for future biomechanical, surgical, and in vitro studies utilizing the rabbit stifle as a model for human knee joint degenerative diseases