DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

Covering behavior of deep-water echinoids in Antarctica: possible response to predatory king crabs

This is the final version of the article. Available from Inter Research via the DOI in this record.Covering behavior refers to the propensity of echinoids (Echinoidea) to lift materials from the surrounding environment onto their aboral surfaces using their tube feet and spines. This behavior has been widely documented in regular echinoids from a variety of well-lit, shallow-marine habitats. Covering behavior in the deep sea, however, is rarely observed, and the functional significance of covering when it does occur remains speculative. During a photographic survey of the seafloor off Anvers Island and Marguerite Bay along the western Antarctic Peninsula, we imaged 11 benthic transects at depths ranging from 390 to 2100 m. We recorded the number of echinoid species, incidence of covering behavior, types of materials used for covering, potential predators of echinoids, and potential prey items for predators. The echinoid Sterechinus spp. was found at all depths, and the percentage of individuals exhibiting covering behavior increased with depth between 390 and 1500 m. There was a significant positive correlation between the incidence of covering behavior in Sterechinus spp. and the density of king crabs (Anomura: Lithodidae), crushing predators that may be expanding their bathymetric range up the Antarctic continental slope as a consequence of ongoing climatic warming. In contrast, covering behavior was not positively correlated with the densities of non-crab predators, the total densities of predators, or the availability of prey. Our results document rarely observed covering behavior in echinoids living in the deep sea and suggest that covering could be a behavioral response to predation pressure by king crabs.We thank the crew of the RV ‘Nathaniel B. Palmer’ during the NBP13-10 cruise for logistical help, as well as J. S. Anderson, A. Brown, C. Easson, D. Ellis, S. Thatje, and S. C. Vos. Thanks also to Paul Dayton as well as 2 anonymous reviewers who offered constructive comments and suggestions. Funding was provided by grants from the US National Science Foundation to R.B.A. (ANT- 1141877) and J.B.M. (ANT-1141896). This paper is contribution no. 160 from the Institute for Research on Global Climate Change at the Florida Institute of Technology

Formulation of complementary food using amaranth, chickpea and maize improves iron, calcium and zinc content

Malnutrition is the cause of the majority of deaths in children under five years old in Ethiopia. Micronutrient deficiencies such as iron, zinc and calcium, often seen in malnourished children, are major public health problems throughout Ethiopia. These deficiencies have negative consequences on the cognitive and physical development of children, and on work productivity of adults. There is, therefore, a need for sustainable methods to address iron inadequacy in complementary feeding. Animal products are a good source of iron, zinc and calcium, but due to their high costs, their consumption by most children in Ethiopia has declined. The grain amaranth grows wild in areas of Ethiopia but is considered a weed. This study, conducted in rural Ethiopia, was initiated to prepare nutrient-rich complementary food using recipes that substituted the usual maize gruel with porridge made from amaranth and chickpea flours. Using a laboratory based experimental study design, four porridges suitable for complementary feeding, with different proportions of amaranth grains, maize and chickpeas were formulated in triplicate and analyzed in triplicate for minerals including iron, and phytate levels. Mother-child pairs were recruited for acceptability testing, at the community level. Results showed adding amaranth improved the content of iron and other nutrients as compared to control porridge (100% maize) and decreased phytate levels. The lowest phytate to iron ratio (0.24) was observed in the 70% amaranth and 30% chickpea blend, and the lowest viscosity measure was also observed in this same formulation. Soaking amaranth seeds in warm (50oC) water then germinating in lemon juice-containing water at 32oC for 72 hours resulted in the lowest phytate levels. In sensory testing, all of the formulated porridges with different proportions of amaranth flour were acceptable to mothers and their children, although the red color was disliked by mothers and their children. Flavor preference was not altered; however, overall acceptability was reduced with increasing amounts of amaranth. The study indicated that a processed 70% amaranth and 30% chickpea product can be used to produce low-cost, nutrient-rich complementary food with moderate acceptability. Increased nutritional awareness, production and consumption of grain amaranth products may be the way to address mineral deficiencies including iron, in the study area.Keywords: Micronutrients, Phytates, Complementary feeding, Amaranth grain, Chickpea, Ethiopia, Iron, Zinc

Application of Bayesian analysis to the doubly labelled water method for total energy expenditure in humans.

RATIONALE: The doubly labelled water (DLW) method is the reference method for the estimation of free-living total energy expenditure (TEE). In this method, where both 2 H and 18 O are employed, different approaches have been adopted to deal with the non-conformity observed regarding the distribution space for the labels being non-coincident with total body water. However, the method adopted can have a significant effect on the estimated TEE. METHODS: We proposed a Bayesian reasoning approach to modify an assumed prior distribution for the space ratio using experimental data to derive the TEE. A Bayesian hierarchical approach was also investigated. The dataset was obtained from 59 adults (37 women) who underwent a DLW experiment during which the 2 H and 18 O enrichments were measured using isotope ratio mass spectrometry (IRMS). RESULTS: TEE was estimated at 9925 (9106-11236) [median and interquartile range], 9646 (9167-10540), and 9,638 (9220-10340) kJ·day-1 for women and at 13961 (12851-15347), 13353 (12651-15088) and 13211 (12653-14238) kJ·day-1 for men, using normalized non-Bayesian, independent Bayesian and hierarchical Bayesian approaches, respectively. A comparison of hierarchical Bayesian with normalized non-Bayesian methods indicated a marked difference in behaviour between genders. The median difference was -287 kJ·day-1 for women, and -750 kJ·day-1 for men. In men there is an appreciable compression of the TEE distribution obtained from the hierarchical model compared with the normalized non-Bayesian methods (range of TEE 11234-15431 kJ·day-1 vs 10786-18221 kJ·day-1 ). An analogous, yet smaller, compression is seen in women (7081-12287 kJ·day-1 vs 6989-13775 kJ·day-1 ). CONCLUSIONS: The Bayesian analysis is an appealing method to estimate TEE during DLW experiments. The principal advantages over those obtained using the classical least-squares method is the generation of potentially more useful estimates of TEE, and improved handling of outliers and missing data scenarios, particularly if a hierarchical model is used

Intraoperative positioning related injury of superficial radial nerve after shoulder arthroscopy – a rare iatrogenic injury: a case report

Arthroscopy of the shoulder is a well-established and routine procedure. The role is expected to increase further with an ever-increasing list of indications reflecting the gratifying results. Intraoperative injuries of nerves related to positioning are known but, fortunately, rare with shoulder arthroscopy. Appropriate assessment of patient and careful positioning is paramount in prevention of these injuries. Despite robust preventive measures, these injuries continue to occur from time to time. Although there are few reports of position-related intraoperative nerve injuries associated with shoulder arthroscopy, the involvement of superficial radial nerve (SRN) has never been described before. We report a rare case of positioning related injury of SRN in a 35-year-old female after arthroscopic rotator cuff repair and discuss the preventive and legal aspects. To authors' knowledge this is the first reported case of intraoperative positioning related injury of SRN

Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months

BackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures

Adaptation of in vitro cytoadherence assay to Plasmodium knowlesi field isolates

P. knowlesi was the first Plasmodium species in which antigenic variation was observed. Variation was due to schizont infected cell agglutination (SICAvar) antigens expressed by the parasite and transported to the exposed surface of the host erythrocyte [1]. PfEMP1 is P. falciparum’s orthologue of P. knowlesi’s SICA proteins [2]. In P. falciparum PfEMP1 is associated with infected erythrocytes binding to receptors such as ICAM-1 expressed on the endothelial cells of the host microvasculature. Here, we use a static protein assay [3] to determine if naturally occurring human P. knowlesi infections can cause erythrocytes to bind to ICAM-1, VCAM-1 and CD36