A gene signature for post-infectious chronic fatigue syndrome

Background: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment

Cross-cultural color-odor associations

Colors and odors are associated; for instance, people typically match the smell of strawberries to the color pink or red. These associations are forms of crossmodal correspondences. Recently, there has been discussion about the extent to which these correspondences arise for structural reasons (i.e., an inherent mapping between color and odor), statistical reasons (i.e., covariance in experience), and/or semantically-mediated reasons (i.e., stemming from language). The present study probed this question by testing color-odor correspondences in 6 different cultural groups (Dutch, Netherlands-residing-Chinese, German, Malay, Malaysian-Chinese, and US residents), using the same set of 14 odors and asking participants to make congruent and incongruent color choices for each odor. We found consistent patterns in color choices for each odor within each culture, showing that participants were making non-random color-odor matches. We used representational dissimilarity analysis to probe for variations in the patterns of color-odor associations across cultures; we found that US and German participants had the most similar patterns of associations, followed by German and Malay participants. The largest group differences were between Malay and Netherlands-resident Chinese participants and between Dutch and Malaysian-Chinese participants. We conclude that culture plays a role in color-odor crossmodal associations, which likely arise, at least in part, through experience

Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. MATERIALS AND METHODS: During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. RESULTS: An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT. The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. CONCLUSION: IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs

A Low-Cost GPS GSM/GPRS Telemetry System: Performance in Stationary Field Tests and Preliminary Data on Wild Otters (Lutra lutra)

Background: Despite the increasing worldwide use of global positioning system (GPS) telemetry in wildlife research, it has never been tested on any freshwater diving animal or in the peculiar conditions of the riparian habitat, despite this latter being one of the most important habitat types for many animal taxa. Moreover, in most cases, the GPS devices used have been commercial and expensive, limiting their use in low-budget projects. Methodology/Principal Findings: We have developed a low-cost, easily constructed GPS GSM/GPRS (Global System for Mobile Communications/General Packet Radio Service) and examined its performance in stationary tests, by assessing the influence of different habitat types, including the riparian, as well as water submersion and certain climatic and environmental variables on GPS fix-success rate and accuracy. We then tested the GPS on wild diving animals, applying it, for the first time, to an otter species (Lutra lutra). The rate of locations acquired during the stationary tests reached 63.2%, with an average location error of 8.94 m (SD = 8.55). GPS performance in riparian habitats was principally affected by water submersion and secondarily by GPS inclination and position within the riverbed. Temporal and spatial correlations of location estimates accounted for some variation in the data sets. GPS-tagged otters also provided accurate locations and an even higher GPS fix-success rate (68.2%). Conclusions/Significance: Our results suggest that GPS telemetry is reliably applicable to riparian and even divin

Relationship between Anaemia, Haemolysis, Inflammation and Haem Oxygenase-1 at Admission with Sepsis: a pilot study

Upregulation of haem oxygenase-1 (HO-1), due to haemolysis and/or inflammation, can lead to impaired immune function. Anaemia is common among sepsis patients, but the consequences of sepsis-associated anaemia are poorly understood. Here, our objective was to determine the prevalence and extent of anaemia, haemolysis, inflammation, and HO-1 induction after early hospital admission. We hypothesised that inflammation- or infection-induced haemolysis contributes to sepsis-associated anaemia and that this will lead to expression of HO-1. In this study, plasma obtained from seventy adult patients within 12 hours of admission to intensive care due to sepsis were analysed for anaemia, haemolysis and inflammatory markers by ELISA and microbead array. The majority (82.6%) of patients were anaemic with evidence of haemolysis (raised haem, haptoglobin, haemopexin, and HO-1 concentrations). Interestingly, concentrations of both haemoglobin and IL-10 were moderately positively correlated with HO-1 concentration (Hb: r = 0.32, p = 0.007; IL-10 r = 0.39, p = 0.0008) whereas HO-1 concentration was weakly negatively correlated with haemopexin (r = -0.23, p = 0.055). Anaemia, while common, was not associated with HO-1 concentration. After adjusting for confounding, HO-1 induction appears to be associated primarily with IL-10 concentration rather than haemolysis. Disease severity at diagnosis was correlated with early plasma IL-10 (r = 0.35, p = 0.003) and HO-1 (r = 0.24, p = 0.048) concentrations. Notably, admission levels of haem, HO-1, and IL-10 were indicators of survival

Addressing Cancer Disparities via Community Network Mobilization and Intersectoral Partnerships: A Social Network Analysis

Community mobilization and collaboration among diverse partners are vital components of the effort to reduce and eliminate cancer disparities in the United States. We studied the development and impact of intersectoral connections among the members of the Massachusetts Community Network for Cancer Education, Research, and Training (MassCONECT). As one of the Community Network Program sites funded by the National Cancer Institute, this infrastructure-building initiative utilized principles of Community-based Participatory Research (CBPR) to unite community coalitions, researchers, policymakers, and other important stakeholders to address cancer disparities in three Massachusetts communities: Boston, Lawrence, and Worcester. We conducted a cross-sectional, sociometric network analysis four years after the network was formed. A total of 38 of 55 members participated in the study (69% response rate). Over four years of collaboration, the number of intersectoral connections reported by members (intersectoral out-degree) increased, as did the extent to which such connections were reported reciprocally (intersectoral reciprocity). We assessed relationships between these markers of intersectoral collaboration and three intermediate outcomes in the effort to reduce and eliminate cancer disparities: delivery of community activities, policy engagement, and grants/publications. We found a positive and statistically significant relationship between intersectoral out-degree and community activities and policy engagement (the relationship was borderline significant for grants/publications). We found a positive and statistically significant relationship between intersectoral reciprocity and community activities and grants/publications (the relationship was borderline significant for policy engagement). The study suggests that intersectoral connections may be important drivers of diverse intermediate outcomes in the effort to reduce and eliminate cancer disparities. The findings support investment in infrastructure-building and intersectoral mobilization in addressing disparities and highlight the benefits of using CBPR approaches for such work

Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

BACKGROUND: Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDINGS: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001). CONCLUSIONS: This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs

Yeast Screens Identify the RNA Polymerase II CTD and SPT5 as Relevant Targets of BRCA1 Interaction

BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1. These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1) to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, NUP188, POM34) and cytoplasmic mRNA decay at P-bodies (CCR4, DHH1). Strikingly, BRCA1 interacted with the phosphorylated RNA polymerase II (RNAPII) carboxy terminal domain (P-CTD), phosphorylated in the pattern specified by the CTDK-I kinase, to induce DEF1-dependent cleavage and accumulation of a RNAPII fragment containing the P-CTD. Significantly, breast cancer associated BRCT domain defects in BRCA1 that suppressed P-CTD cleavage and lethality in yeast also suppressed the physical interaction of BRCA1 with human SPT5 in breast epithelial cells, thus confirming SPT5 as a relevant target of BRCA1 interaction. Furthermore, enhanced P-CTD cleavage was observed in both yeast and human breast cells following UV-irradiation indicating a conserved eukaryotic damage response. Moreover, P-CTD cleavage in breast epithelial cells was BRCA1-dependent since damage-induced P-CTD cleavage was only observed in the mutant BRCA1 cell line HCC1937 following ectopic expression of wild type BRCA1. Finally, BRCA1, SPT5 and hyperphosphorylated RPB1 form a complex that was rapidly degraded following MMS treatment in wild type but not BRCA1 mutant breast cells. These results extend the mechanistic links between BRCA1 and transcriptional consequences in response to DNA damage and suggest an important role for RNAPII P-CTD cleavage in BRCA1-mediated cancer suppression

Evaluation of an Antimicrobial L-Amino Acid Oxidase and Peptide Derivatives from Bothropoides mattogrosensis Pitviper Venom

Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms