389 research outputs found

    Note on Moufang-Noether currents

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    The derivative Noether currents generated by continuous Moufang tranformations are constructed and their equal-time commutators are found. The corresponding charge algebra turns out to be a birepresentation of the tangent Mal'ltsev algebra of an analytic Moufang loop.Comment: LaTeX2e, 6 pages, no figures, presented on "The XVth International Colloquium on Integrable Systems and Quantum Symmetries, Prague, 15-17 June, 2006

    Phosphatidylethanolamine N-methyltransferase (PEMT) Knockout Mice Exhibit Worse Alcohol-Induced Liver Injury than Wildtype Mice

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    Phosphatidylethanolamine N-methyltransferase (PEMT) is an enzyme that catalyzes the successive transfer of 3 methyl groups from S-adenosylmethionine (SAM) to phosphatidylethanolamine (PE) to generate phosphatidylcholine (PC). PC is vital for exporting fat out of the liver, ultimately preventing hepatic steatosis. Alcohol also induces steatosis partly through damaging this pathway, so the purpose of this study was to investigate the relationship between alcohol and PEMT in the liver. PEMT -/- (KO) and wild-type (WT) mice were subjected to a chronic + binge alcohol treatment, and both serum and liver samples were analyzed. Triglyceride quantification, SAM and S-adenosylhomocysteine (SAH) levels, and histological analyses were performed on liver samples, while ALT levels were determined from serum samples. Our study showed that ethanol-fed PEMT KO mice exhibited worse liver injury compared to other treatment groups. Our results show increased triglyceride levels, increased ALT levels, decreased SAM:SAH ratio, and increased liver to body weight ratio. From these findings, we conclude that additional liver damage is observed with the combination of alcohol feeding and absence of the PEMT enzyme. The mechanism by which these two factors affect one another is a key area of future study.https://digitalcommons.unmc.edu/surp2021/1016/thumbnail.jp

    The Efficacy of Renal Replacement Therapy for Rewarming of Patients in Severe Accidental Hypothermia-Systematic Review of the Literature.

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    Renal replacement therapy (RRT) can be used to rewarm patients in deep hypothermia. However, there is still no clear evidence for the effectiveness of RRT in this group of patients. This systematic review aims to summarize the rewarming rates during RRT in patients in severe hypothermia, below or equal to 32 °C. This systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (identifier CRD42021232821). We searched Embase, Medline, and Cochrane databases using the keywords hypothermia, renal replacement therapy, hemodialysis, hemofiltration, hemodiafiltration, and their abbreviations. The search included only articles in English with no time limit, up until 30 June 2021. From the 795 revised articles, 18 studies including 21 patients, were selected for the final assessment and data extraction. The mean rate of rewarming calculated for all studies combined was 1.9 °C/h (95% CI 1.5-2.3) and did not differ between continuous (2.0 °C/h; 95% CI 0.9-3.0) and intermittent (1.9 °C/h; 95% CI 1.5-2.3) methods (p > 0.9). Based on the reviewed literature, it is currently not possible to provide high-quality recommendations for RRT use in specific groups of patients in accidental hypothermia. While RRT appears to be a viable rewarming strategy, the choice of rewarming method should always be determined by the specific clinical circumstances, the available resources, and the current resuscitation guidelines

    Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System

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    Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable of causing severe infections. S. aureus virulence is controlled by the agr quorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase. agr loci are found also in other staphylococcal species and for Staphylococcus epidermidis, the encoded AIP represses expression of agr regulated virulence genes in S. aureus. In this study we aimed to better understand the interaction between staphylococci and S. aureus, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target S. aureus infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit S. aureus agr. The dog pathogen, Staphylococcus schleiferi, expressed the most potent inhibitory activity and was active against all four agr classes found in S. aureus. By employing a S. aureus strain encoding a constitutively active AIP receptor we show that the activity is mediated via agr. Subsequent cloning and heterologous expression of the S. schleiferi AIP in S. aureus demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic S. schleiferi AIP was able to completely abolish agr induction of an S. aureus reporter strain. To assess impact on S. aureus virulence, we co-inoculated S. aureus and S. schleiferi in vivo in the Galleria mellonella wax moth larva, and found that expression of key S. aureus virulence factors was abrogated. Our data show that the S. aureus agr locus is highly responsive to other staphylococcal species suggesting that agr is an inter-species communication system. Based on these results we speculate that interactions between S. aureus and other colonizing staphylococci will significantly influence the ability of S. aureus to cause infection, and we propose that other staphylococci are potential sources of compounds that can be applied as anti-virulence therapy for combating S. aureus infections

    Elevated S-Adenosylhomocysteine Induces Adipocyte Dysfunction to Promote Alcohol-Associated Liver Steatosis

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    It has been previously shown that chronic ethanol administration-induced increase in adipose tissue lipolysis and reduction in the secretion of protective adipokines collectively contribute to alcohol-associated liver disease (ALD) pathogenesis. Further studies have revealed that increased adipose S-adenosylhomocysteine (SAH) levels generate methylation defects that promote lipolysis. Here, we hypothesized that increased intracellular SAH alone causes additional related pathological changes in adipose tissue as seen with alcohol administration. To test this, we used 3-deazaadenosine (DZA), which selectively elevates intracellular SAH levels by blocking its hydrolysis. Fully differentiated 3T3-L1 adipocytes were treated in vitro for 48 h with DZA and analysed for lipolysis, adipokine release and differentiation status. DZA treatment enhanced adipocyte lipolysis, as judged by lower levels of intracellular triglycerides, reduced lipid droplet sizes and higher levels of glycerol and free fatty acids released into the culture medium. These findings coincided with activation of both adipose triglyceride lipase and hormone sensitive lipase. DZA treatment also significantly reduced adipocyte differentiation factors, impaired adiponectin and leptin secretion but increased release of pro-inflammatory cytokines, IL-6, TNF and MCP-1. Together, our results demonstrate that elevation of intracellular SAH alone by DZA treatment of 3T3-L1 adipocytes induces lipolysis and dysregulates adipokine secretion. Selective elevation of intracellular SAH by DZA treatment mimics ethanol\u27s effects and induces adipose dysfunction. We conclude that alcohol-induced elevations in adipose SAH levels contribute to the pathogenesis and progression of ALD

    Acute Ethanol-Induced Liver Injury is Prevented by Betaine Administration

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    Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (n = 5/group) were gavaged with 4 g betaine/kg BW, either 2 h before or simultaneously with the ethanol or saline gavages. All mice were sacrificed 8 h after the last gavage and serum and liver parameters were quantified. Ethanol binges caused a 50% decrease in hepatic SAM:SAH ratio and a \u3e3-fold rise in liver triglycerides (p ≤ 0.05). These latter changes were accompanied by elevated serum AST and ALT activities and blood alcohol concentrations (BAC) that were ∼three-times higher than the legal limit of intoxication in humans. Mice that were treated with betaine 2 h before or simultaneously with the ethanol binges exhibited similar BAC as in mice given ethanol-alone. Both betaine treatments significantly elevated hepatic SAM levels thereby normalizing the SAM:SAH ratio and attenuating hepatic steatosis and other injury parameters, compared with mice given ethanol alone. Simultaneous betaine co-administration with ethanol was more effective in preventing or attenuating liver injury than betaine given before ethanol gavage. Our findings confirm the potential therapeutic value of betaine administration in preventing liver injury after binge drinking in an animal model

    Data and methods to calculate cut-off values for serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest.

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    The data and estimation methods presented in this article are associated with the research article, "Cut-off values of serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest: a retrospective multi-centre study" [1]. In this article we estimate recommended cut-off values for in-hospital triage with respect to extracorporeal rewarming. With only 6 survivors of 103 patients collected over a period of 20 years the ability to estimate reliable threshold values is limited. In addition, because the number of avalanche victims is also limited, a significantly larger dataset is unlikely to be obtained. We have therefore adapted two non-parametric estimation methods (bootstrapping and exact binomial distribution) to our specific needs and performed a simulations to confirm validity and reliability

    The exponential law: Monopole detectors, Bogoliubov transformations, and the thermal nature of the Euclidean vacuum in RP^3 de Sitter spacetime

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    We consider scalar field theory on the RP^3 de Sitter spacetime (RP3dS), which is locally isometric to de Sitter space (dS) but has spatial topology RP^3. We compare the Euclidean vacua on RP3dS and dS in terms of three quantities that are relevant for an inertial observer: (i) the stress-energy tensor; (ii) the response of an inertial monopole particle detector; (iii) the expansion of the Euclidean vacuum in terms of many-particle states associated with static coordinates centered at an inertial world line. In all these quantities, the differences between RP3dS and dS turn out to fall off exponentially at early and late proper times along the inertial trajectory. In particular, (ii) and (iii) yield at early and late proper times in RP3dS the usual thermal result in the de Sitter Hawking temperature. This conforms to what one might call an exponential law: in expanding locally de Sitter spacetimes, differences due to global topology should fall off exponentially in the proper time.Comment: 22 pages, REVTex v3.1 with amsfonts and epsf, includes 2 eps figures. (v2: Minor typos corrected, references updated.
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