Radically different maxicircle classes within the same kinetoplast: an artefact or a novel feature of the kinetoplast genome?

We discuss here some results which suggest that radically different maxicircle classes coexist within the same kinetoplast. These data, although tentative and incomplete, may provide a new outlook on the kinetoplast genome structure and expression

Incidence and severity of postoperative complications following oral, periodontal, and implant surgeries: A retrospective study

Background: Incidence and severity of postoperative complications are key elements in determining the riskâ benefit relationship of any surgical procedure. The aim of this retrospective study was to assess and categorize the postoperative complications that occur following, and are associated with, oral, periodontal, and implant surgeries.Methods: A total of 3,900 patients who underwent surgical procedures including, but not limited to, sinus floor elevation, guided tissue regeneration, crown lengthening, implant placement, soft tissue graft, open flap debridement or surgical removal of impacted teeth were included. Postoperative complications were recorded and graded based on impedance to routine daily activity and favorable surgical outcomes. Regression models were generated to evaluate correlations between complication types, as well as between patient/surgical characteristics and the incidence of complications.Results: Surgical removal of impacted teeth and lateral sinus floor elevation had the highest incidence and severity of complications. Postoperative dentinal hypersensitivity (5.7%) was the most frequent complication, followed by excessive pain (4.1%), and moderate postoperative bleeding (3.5%). Based on the devised grading system described in this paper, the complications were 11.1% of Grade I, 3.3% of Grade II, 8.3% of Grade III, 0.1% of Grade IV, and no complications recorded under Grades V or VI.Conclusions: Surgical removal of impacted teeth and lateral sinus floor elevation are more prone to more severe complications compared with other procedures. Additionally, complications that do not impede favorable surgical outcomes and/or routine daily activity are the most likely to occur. Smoking and diabetes are generally associated with postoperative complications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153087/1/jper10367.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153087/2/jper10367_am.pd

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Measuring every particle's size from three-dimensional imaging experiments

Often experimentalists study colloidal suspensions that are nominally monodisperse. In reality these samples have a polydispersity of 4-10%. At the level of an individual particle, the consequences of this polydispersity are unknown as it is difficult to measure an individual particle size from microscopy. We propose a general method to estimate individual particle radii within a moderately concentrated colloidal suspension observed with confocal microscopy. We confirm the validity of our method by numerical simulations of four major systems: random close packing, colloidal gels, nominally monodisperse dense samples, and nominally binary dense samples. We then apply our method to experimental data, and demonstrate the utility of this method with results from four case studies. In the first, we demonstrate that we can recover the full particle size distribution {\it in situ}. In the second, we show that accounting for particle size leads to more accurate structural information in a random close packed sample. In the third, we show that crystal nucleation occurs in locally monodisperse regions. In the fourth, we show that particle mobility in a dense sample is correlated to the local volume fraction.Comment: 7 pages, 5 figure

Methamphetamine and Viagra Use: Relationship to Sexual Risk Behaviors

Recent studies show that Viagra and methamphetamine use are associated with unprotected anal intercourse among men who have sex with men (MSM). In Long Beach, California, we have reported on an association between Viagra use and the use of amphetamines during sex. The current research investigated the use of both Viagra and amphetamine in men in Long Beach, California. Data on 1,839 men recruited into HIV prevention and testing programs were collected using the Risk Behavior Assessment. A generalized logit model was constructed comparing ever having used both amphetamine and Viagra together and separately, as compared to never having used either (referent). Men who used both methamphetamine and Viagra showed a significantly higher prevalence of hepatitis B, syphilis, and HIV compared to those who used only one or neither drug. Of the 1,794 complete cases, 11.1% (199/1794) had used both amphetamine and Viagra. Of 20 potential risk and protective factors for use of amphetamine and Viagra, 12 were significant predictors: ever used gamma-hydroxybutyrate (GHB), ever used cocaine, ever used ecstasy, being infected with HIV, race = White compared to other, ever having hepatitis B, ever using crack, ever given money to have sex, living in a hotel, ever been in drug treatment, and ever using heroin. The protective factor was being heterosexual. Viagra use was associated with insertive, and methamphetamine was associated with receptive, anal intercourse. GHB use appears to play a more important role than previously thought

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

Quantum fluctuations can promote or inhibit glass formation

The very nature of glass is somewhat mysterious: while relaxation times in glasses are of sufficient magnitude that large-scale motion on the atomic level is essentially as slow as it is in the crystalline state, the structure of glass appears barely different than that of the liquid that produced it. Quantum mechanical systems ranging from electron liquids to superfluid helium appear to form glasses, but as yet no unifying framework exists connecting classical and quantum regimes of vitrification. Here we develop new insights from theory and simulation into the quantum glass transition that surprisingly reveal distinct regions where quantum fluctuations can either promote or inhibit glass formation.Comment: Accepted for publication in Nature Physics. 22 pages, 3 figures, 1 Tabl

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection