The Osmolytic Effect and Its Action on Topoisomerase-I

While the presence of water within biological systems is acknowledged to be of utmost importance, its specific role at the molecular level within these systems has only recently been studied carefully. Of particular interest are the effects of water on the interactions that occur between topoisomerase-I and DNA. Topoisomerase-I relaxes supercoiled DNA, a process critical for cellular processes such as transcription and replication. Relaxation occurs when the enzyme breaks one strand of the double-stranded DNA, rotates a broken end around the intact strand, and rejoins the two broken ends. consequently changing the linking number of the supercoiled DNA by an increment of one. While it is well known that water acts during the catalytic mechanism of the enzyme to hydrolyze the phosphate backbone, other effects of water have not been explored. Through the osmotic stress method, the role and amount of water involved in the interaction between topoisomearase-I and DNA with regard to enzymatic activity has been investigated. Four osmolytes (PEG 6000, PEG 600, betaine, and sucrose) were introduced into the reaction at varying concentrations (molality), which is related to the osmotic pressure (osmolality). Results of the osmolytes on the catalytic activity of the enzyme were visualized and analyzed through the quantification of topoisomer band 111 intensity, providing the percentage of DNA under these conditions that is converted to the relaxed form. Our preliminary data suggests that the presence of osmolytes attenuates the catalytic activity of topoisomerase-I. Thus, it appears that water may play an important role in stabilizing the enzyme-substrate complex, enabling normal catalytic activity of topoisomerase-I. I

Nickel Reduces Calcium Dependent Dimerization In Neural Cadherin

Cadherins are the primary transmembrane component in adherens junctions, structures that link the actin cytoskeleton in adjacent cells within solid tissues including neurological synapses, epithelium and endothelium. Cell-cell adhesion by cadherins requires the binding of calcium ions to specific sites in the extracellular region. Given the complexity of the cell adhesion microenvironment, we are investigating whether other divalent cations might affect calciumdependent dimerization of neural-(N-) cadherin. The first chapter focuses on studies to characterize the impact of binding physiological magnesium (II) or neurotoxic nickel (II) on calcium-dependent N-cadherin function. Physiological levels of magnesium have only a small effect on the calcium-binding affinity and calcium-induced dimerization of N-cadherin. However, a tenfold lower concentration of nickel decreases the apparent calcium-binding affinity and calcium-induced dimerization of N-cadherin. Competitive binding studies indicate that the apparent dissociation constants for nickel and magnesium are 0.2 mM and 2.5 mM, respectively. These Kd values are consistent with concentrations observed for a range of divalent cations in the extracellular space. Results from these studies indicate that calcium-induced dimerization by Ncadherin is attenuated by natural and non-physiological divalent cations in the extracellular microenvironment. The second chapter will detail my contributions to studies into the effect of pH on the structure and function of neural cadherin that utilize many of the same analytical techniques

Book Reviews

Non peer reviewedPublisher PD

The MDCK variety pack: choosing the right strain

The MDCK cell line provides a tractable model for studying protein trafficking, polarity and junctions (tight, adherens, desmosome and gap) in epithelial cells. However, there are many different strains of MDCK cells available, including the parental line, MDCK I, MDCK II, MDCK.1, MDCK.2, superdome and supertube, making it difficult for new researchers to decide which strain to use. Furthermore, there is often inadequate reporting of strain types and where cells were obtained from in the literature. This review aims to provide new researchers with a guide to the different MDCK strains and a directory of where they can be obtained. We also hope to encourage experienced researchers to report the stain and origin of their MDCK cells

HOUSEHOLDS' EXPERIENCES WITH THE RED IMPORTED FIRE ANT IN SOUTH CAROLINA

The red imported fire ant (Solenopsis invicta), abbreviated as RIFA, is believed to have been brought by accident to Mobile, Alabama in the 1930s via ship ballast from South America. The RIFA was first reported in Charleston and Orangeburg counties in South Carolina in 1952 and has since spread to all 46 counties in the state. The RIFA has had adverse impacts on the environments it has infested. In natural environments, the young of ground-nesting insects, reptiles, birds and mammals are subject to RIFA predation. In agriculture, the RIFA damages crops and livestock. The RIFA poses a health threat to humans, as it is aggressive and has a venomous sting. To learn more about the current impacts of the RIFA, a random sample of South Carolina households was conducted between November 1998 and January 1999. This report summarizes the survey results.Environmental Economics and Policy,

DetectiV: visualization, normalization and significance testing for pathogen-detection microarray data

DetectiV is a tool for analyzing pathogen-detection microarray datasets that allows simple visualisation, normalisation and significance testing

Tumour inflammatory infiltrate predicts survival following curative resection for node-negative colorectal cancer

<b>Background</b>: A pronounced tumour inflammatory infiltrate is known to confer a good outcome in colorectal cancer. Klintrup and colleagues reported a structured assessment of the inflammatory reaction at the invasive margin scoring low grade or high grade. The aim of the present study was to examine the prognostic value of tumour inflammatory infiltrate in node-negative colorectal cancer. <b>Methods</b>: Two hundred patients had undergone surgery for node-negative colorectal cancer between 1997 and 2004. Specimens were scored with Jass’ and Klintrup’s criteria for peritumoural infiltrate. Pathological data were taken from the reports at that time. <b>Results</b>: Low-grade inflammatory infiltrate assessed using Klintrup’s criteria was an independent prognostic factor in node-negative disease. In patients with a low-risk Petersen Index (n = 179), low-grade infiltrate carried a threefold increased risk of cancer death. Low-grade infiltrate was related to increasing T stage and an infiltrating margin. <b>Conclusion</b>: Assessment of inflammatory infiltrate using Klintrup’s criteria provides independent prognostic information on node-negative colorectal cancer. A high-grade local inflammatory response may represent effective host immune responses impeding tumour growth

Antibiotic prescribing in patients with self-reported sore throat.

Objectives: To investigate the predictors of general practitioner (GP) consultation and antibiotic use in those developing sore throat. Methods: We conducted a prospective population-based cohort study on 4461 participants in two rounds (2010-11) from 1897 households. Results: Participants reported 2193 sore throat illnesses, giving a community sore throat incidence of 1.57/ person-year. 13% of sore throat illnesses led to a GP consultation and 56% of these consultations led to antibiotic use. Participants most likely to have sore throats included women and children (e.g. school compared with retirement age); adjusted incidence rate ratio (aIRR) of 1.33 and 1.52, respectively. Participants with sore throat were more likely to consult their GP if they were preschool compared with retirement age [adjusted OR (aOR) 3.22], had more days of sore throat (aOR 1.11), reported more severe pain (aOR 4.24) or reported fever (aOR 3.82). Antibiotics were more often used by chronically ill individuals (aOR 1.78), those reporting severe pain (aOR 4.14), those reporting fever (aOR 2.58) or children with earache (aOR 1.85). Among those who consulted, males and adults who reported feeling anxious were more likely to use antibiotics; aOR 1.87 and 5.36, respectively. Conclusions: Only 1 in 10 people who have a sore throat see a doctor and more than half of those attending get antibiotics. Further efforts to curb antibiotic use should focus on reducing initial GP consultations through public information promoting safe self-management, targeted at groups identified above as most likely to attend with sore throats

Climate Change and Indiana’s Energy Sector: A Report from the Indiana Climate Change Impacts Assessment

Indiana’s climate and its manufacturing-heavy economy make it a prime user of energy. In fact, Indiana is the ninth-most energy intensive state per capita in the country. Nearly three-quarters of Indiana’s electricity comes from coal, and 5 percent is generated by renewable sources, though the wind energy sector is growing and coal use is declining. This energy mix makes the Hoosier State the eighth-largest emitter of climate-changing gases, at 183 million metric tons of carbon dioxide (CO2) emitted per year. As global and local climates continue to shift, it is important to know how Indiana’s future energy profile will be affected and what those changes mean for Hoosier families and businesses. This report from the Indiana Climate Change Impacts Assessment (IN CCIA) looks at projected changes to Indiana’s residential and commercial energy demands as the state warms, and to Indiana’s energy supply over the coming century