TonB Not Directly Related to Efflux of Antibiotics in E. coli

Studies in Pseudomonas aeruginosa have suggested that the TonB energy transduction system directly contributes to efflux-mediated antibiotic resistance, ostensibly by energizing one or more efflux systems. We have found ∆tonB strains of Escherichia coli to similarly be more sensitive to certain antibiotics relative to wild-type strains. To test the hypothesis that this enhanced sensitivity involved the energization of efflux systems, sensitivity patterns for a variety of antibiotics were evaluated using a set of strains differentially lacking genes encoding the Acr efflux system, the universal outer membrane efflux portal TolC, and TonB. No correlation was evident between the resistance phenotypes of TonB system mutants and efflux mutants. Addition comparisons using Tol system components excluded the possibility that the increased sensitivity of TonB strains involved disruption of the barrier function of the outer membrane. Further comparisons, using strains in which iron transport was altered and cells were grown under iron limiting conditions, suggest that enhanced sensitivity to select antibiotics is simply another aspect of the pleomorphic tonB phenotype attributable to iron starvation. Understanding the TonB system is important for public health

Analysis of FY Promoter and Hepatocystis Load in South African Vervet Monkeys (Chlorocebus Aethiops)

There are species of Hepatocystis and Plasmodium, related blood parasites, that enter the cell through a chemokine receptor, coded for by the Duffy antigen/receptor for chemokines in humans, and the FY*0 (FY Null) allele in the promoter of this gene results in the absence of this receptor on the exterior of the cell (Miller et al., 1977; Miller et al., 1975; Miller et al., 1976; Barnwell et al., 1989; Perkins and Schall, 2002; Martinsen et al., 2008; Tung et al., 2009). Humans without the receptor show resistance to multiple strains of Plasmodium (Tournamelle, et al., 1995; Zimmerman, et al. 1999; Michon et al., 2001). Allelic variation at the FY gene, a homologous area in nonhuman primates, impacts resistance to Hepatocystis and Plasmodium infection in some nonhuman primates (Schmidt et al., 1977; Tung et al., 2009; Butcher et al. 2010). The current study looks at the FY promoter region in vervet monkeys (Chlorocebus aethiops) to see if there are interactions between allelic variation of this gene and Hepatocystis infection. Hepatocystis infection was detected in South African vervet monkeys for the first time, and variation was found in the FY promoter region of vervet monkeys. There were eight nucleotide positions that showed variance, and there were nine different alleles of the FY gene promoter that were found

Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation.

It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice. Given the known contribution of D1 and D2 dopamine receptors to the neurotoxic effects of amphetamine, we also performed quantitative receptor autoradiography of both receptors in the brains of PTN-Tg and WT mice. D1 and D2 receptors binding in the striatum and other regions of interest was not altered by genotype or treatment. Finally, we found that amphetamine CPP was significantly reduced in PTN-Tg mice. The data demonstrate that PTN overexpression in the brain blocks the conditioning effects of amphetamine and enhances the characteristic striatal dopaminergic denervation caused by this drug. These results indicate for the first time deleterious effects of PTN in vivo by mechanisms that are probably independent of changes in the expression of D1 and D2 dopamine receptors. The data also suggest that PTN-induced neuroinflammation could be involved in the enhanced neurotoxic effects of amphetamine in the striatum of PTN-Tg mice

Two cases of spinal muscular atrophy type II with eosinophilic oesophagitis.

Although primarily characterised by loss of motor neurons from the anterior horn of spinal cord and muscle atrophy, spinal muscular atrophy (SMA) is now recognised as a multi-systemic disorder. Here, we report two SMA Type II patients with eosinophilic oesophagitis (EoE), a rare, chronic immune/antigen-mediated condition. One patient presented with dysphagia and poor weight gain, and the second patient had symptoms of gastro-oesophageal reflux (GOR) and poor weight gain. In both patients, macroscopic observations during gastroscopy indicated typical signs of EoE, which were verified during histological examination of oesophageal biopsies. Given that there is a specific treatment strategy for EoE, these cases highlight the importance of considering this condition in clinical investigations - especially for patients with SMA - who have GOR, discomfort, and oral aversion

Workshop 9: Grant Funding: Where to Find It and How to Get It

Across the country, state funding for institutions of higher education is being cut. One result of these budget cuts is that faculty at state institutions are facing increasing pressure to secure grant funding. This three-hour workshop will guide the participant through the grant development process, starting with how to find grant funding opportunities and ending with how to ensure the proposal includes key components reviewers are expecting