Spatial scale and distribution of neurovascular signals underlying decoding of orientation and eye of origin from fMRI data

Multivariate pattern analysis of functional magnetic resonance imaging (fMRI) data is widely used, yet the spatial scales and origin of neurovascular signals underlying such analyses remain unclear. We compared decoding performance for stimulus orientation and eye of origin from fMRI measurements in human visual cortex with predictions based on the columnar organization of each feature and estimated the spatial scales of patterns driving decoding. Both orientation and eye of origin could be decoded significantly above chance in early visual areas (V1–V3). Contrary to predictions based on a columnar origin of response biases, decoding performance for eye of origin in V2 and V3 was not significantly lower than that in V1, nor did decoding performance for orientation and eye of origin differ significantly. Instead, response biases for both features showed large-scale organization, evident as a radial bias for orientation, and a nasotemporal bias for eye preference. To determine whether these patterns could drive classification, we quantified the effect on classification performance of binning voxels according to visual field position. Consistent with large-scale biases driving classification, binning by polar angle yielded significantly better decoding performance for orientation than random binning in V1–V3. Similarly, binning by hemifield significantly improved decoding performance for eye of origin. Patterns of orientation and eye preference bias in V2 and V3 showed a substantial degree of spatial correlation with the corresponding patterns in V1, suggesting that response biases in these areas originate in V1. Together, these findings indicate that multivariate classification results need not reflect the underlying columnar organization of neuronal response selectivities in early visual areas. NEW & NOTEWORTHY Large-scale response biases can account for decoding of orientation and eye of origin in human early visual areas V1–V3. For eye of origin this pattern is a nasotemporal bias; for orientation it is a radial bias. Differences in decoding performance across areas and stimulus features are not well predicted by differences in columnar-scale organization of each feature. Large-scale biases in extrastriate areas are spatially correlated with those in V1, suggesting biases originate in primary visual cortex

Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10

Background: The peptide apelin is expressed in human healthy livers and is implicated in the development of hepatic fibrosis and cirrhosis. Mutations in the bone morphogenetic protein receptor type II (BMPR-II) result in reduced plasma levels of apelin in patients with heritable pulmonary arterial hypertension. Ligands for BMPR-II include bone morphogenetic protein 9 (BMP9), highly expressed in liver, and BMP10, expressed in heart and to a lesser extent liver. However, it is not known whether reductions in BMP9 and/or BMP10, with associated reduction in BMPR-II signalling, correlate with altered levels of apelin in patients with liver fibrosis and cirrhosis. Methods: Plasma from patients with liver fibrosis (n = 14), cirrhosis (n = 56), and healthy controls (n = 25) was solid-phase extracted using a method optimised for recovery of apelin, which was measured by ELISA. Results: Plasma apelin was significantly reduced in liver fibrosis (8.3 ± 1.2 pg/ml) and cirrhosis (6.5 ± 0.6 pg/ml) patients compared with controls (15.4 ± 2.0 pg/ml). There was no obvious relationship between apelin and BMP 9 or BMP10 previously measured in these patients. Within the cirrhotic group, there was no significant correlation between apelin levels and disease severity scores, age, sex, or treatment with β-blockers. Conclusions: Apelin was significantly reduced in plasma of patients with both early (fibrosis) and late-stage (cirrhosis) liver disease. Fibrosis is more easily reversible and may represent a potential target for new therapeutic interventions. However, it remains unclear whether apelin signalling is detrimental in liver disease or is beneficial and therefore, whether an apelin antagonist or agonist have clinical use

Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

<p>Abstract</p> <p>Background</p> <p>Myxoma virus is a member of the <it>Poxviridae </it>and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy.</p> <p>Results</p> <p>An unusually large number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed that a high proportion of these viral DNA preparations contained a frame-shift mutation within the M135R gene that has previously been identified as a virulence factor. This frame-shift mutation results in expression of a greatly truncated product. The same frame-shift mutation has also been found recently within an avirulent strain of myxoma virus (6918). However, three other frame-shift mutations found in this strain (in the genes M009L, M036L and M148R) were not shared with the Danish viruses but a single nucleotide deletion in the M138R/M139R intergenic region was a common feature.</p> <p>Conclusions</p> <p>It appears that expression of the full-length myxoma virus M135R protein is not required for virulence in rabbits. Hence, the frame-shift mutation in the M135R gene in the nonpathogenic 6918 virus strain is not sufficient to explain the attenuation of this myxoma virus but one/some of the other frame-shift mutations alone or in conjunction with one/some of the thirty two amino acid substitutions must also contribute. The real time PCR assay for myxoma virus is a useful diagnostic tool for laboratory confirmation of suspected cases of myxomatosis.</p

Evolving DNA motifs to predict GeneChip probe performance

Background: Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. Results: Regular expressions can be automatically created from a Backus-Naur form (BNF) context-free grammar using strongly typed genetic programming. Conclusion: The automatically produced motif is better at predicting poor DNA sequences than an existing human generated RE, suggesting runs of Cytosine and Guanine and mixtures should all be avoided. © 2009 Langdon and Harrison; licensee BioMed Central Ltd

Comparison and evaluation of experimental mediastinitis models: precolonized foreign body implants and bacterial suspension inoculation seems promising

BACKGROUND: Post-sternotomy mediastinitis (PSM) is a devastating surgical complication affecting 1–3% of patients that undergo cardiac surgery. Staphylococcus aureus is one of the most commonly encountered bacterial pathogen cultured from mediastinal samples obtained from patients with PSM. A component of the membrane of the gram positive bacteria, lipoteichoic acid, stimulates the blood monocytes and macrophages to secrete cytokines, radicals and nitrogen species leading to oxido-inflammatory damage. This seems to be responsible for the high mortality rate in PSM. For the evaluation of the pathogenesis of infection or for the investigation of alternative treatment models in infection, no standard model of mediastinitis seems to be available. In this study, we evaluated four mediastinitis models in rats. METHODS: The rats were divided into four groups to form different infection models. Group A: A suspension of 1 × 10(7 )colony-forming units Staphylococcus aureus in 0,5 mL was inoculated from the right second intercostal space into the mediastinum. Group B: A hole was created in the right second intercostal space and a piece of stainless-steel implant with a length of 0.5 cm was inserted into the mediastinum and a suspension of 1 × 10(7 )cfu bacteria in 0,5 mL was administered via the tail vein. Group C: Precolonized stainless-steel implant was inserted into the mediastinum. Group D: Precolonized stainless-steel implant was inserted into the mediastinum and the bacteria suspension was also injected into the mediastinum. On the 10(th )day, rats were sacrificed and the extension of infection in the mediastenae was evaluated by quantitative cultures. Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were determined in the sera to evaluate the neutrophil activation and assess the inflammatory oxidation. RESULTS: The degree of infection in group C and D were 83.3% and 100% respectively (P < 0.001). MDA levels were significantly higher in these two groups than the others (P < 0.001). CONCLUSION: Infected implants and high bacterial concentration administration were the two important components that played a significant role in the outcome of a successful infection in mediastinum in a rat model

A cluster-randomised feasibility trial of a children's weight management programme:the Child weigHt mANaGement for Ethnically diverse communities (CHANGE) study

Background: Community-based programmes for children with excess weight are widely available, but few have been developed to meet the needs of culturally diverse populations. We adapted an existing children's weight management programme, focusing on Pakistani and Bangladeshi communities. We report the evaluation of this programme to assess feasibility of programme delivery, acceptability of the programme to participants from diverse communities, and feasibility of methods to inform a future trial. Methods: A cluster-randomised feasibility trial was undertaken in a large UK city. Children's weight management programmes (n = 24) were randomised to be delivered as the adapted or the standard programme (2:1 ratio). Routine data on participant attendance (n = 243) at the sessions were used to estimate the proportion of families completing the adapted and standard programmes (to indicate programme acceptability). Families planning to attend the programmes were recruited to participate in the feasibility study (n = 92). Outcome data were collected from children and parents at baseline, end of programme, and 6 months post-programme. A subsample (n = 24) of those attending the adapted programme participated in interviews to gain their views of the content and delivery and assess programme acceptability. Feasibility of programme delivery was assessed through observation and consultation with facilitators, and data on costs were collected. Results: The proportion of Pakistani and Bangladeshi families and families of all ethnicities completing the adapted programme was similar: 78.8% (95% CI 64.8-88.2%) and 76.3% (95% CI 67.0-83.6%) respectively. OR for completion of adapted vs. standard programme was 2.40 (95% CI 1.32-4.34, p = 0.004). The programme was feasible to deliver with some refinements, and participant interview data showed that the programme was well received. Study participant recruitment was successful, but attrition was high (35% at 6 months). Data collection was mostly feasible, but participant burden was high. Data collection on cost of programme delivery was feasible, but costs to families were more challenging to capture. Conclusions: This culturally adapted programme was feasible to deliver and highly acceptable to participants, with increased completion rates compared with the standard programme. Consideration should be given to a future trial to evaluate its clinical and cost-effectiveness. Trial registration: ISRCTN81798055, registered: 13/05/2014

Population weighted raster maps can communicate findings of social audits: examples from three continents

<p>Abstract</p> <p>Background</p> <p>Maps can portray trends, patterns, and spatial differences that might be overlooked in tabular data and are now widely used in health research. Little has been reported about the process of using maps to communicate epidemiological findings.</p> <p>Method</p> <p>Population weighted raster maps show colour changes over the study area. Similar to the rasters of barometric pressure in a weather map, data are the health occurrence – a peak on the map represents a higher value of the indicator in question. The population relevance of each sentinel site, as determined in the stratified last stage random sample, combines with geography (inverse-distance weighting) to provide a population-weighted extension of each colour. This transforms the map to show population space rather than simply geographic space.</p> <p>Results</p> <p>Maps allowed discussion of strategies to reduce violence against women in a context of political <it>sensitivity</it> about quoting summary indicator figures. <it>Time-series maps</it> showed planners how experiences of health services had deteriorated despite a reform programme; where in a country HIV risk behaviours were improving; and how knowledge of an economic development programme quickly fell off across a region. <it>Change maps</it> highlighted where indicators were improving and where they were deteriorating. Maps of <it>potential impact of interventions</it>, based on multivariate modelling, displayed how partial and full implementation of programmes could improve outcomes across a country. <it>Scale</it> depends on context. To support local planning, district maps or local government authority maps of health indicators were more useful than national maps; but multinational maps of outcomes were more useful for regional institutions. Mapping was useful to illustrate in which districts enrolment in religious schools – a <it>rare occurrence</it> - was more prevalent.</p> <p>Conclusions</p> <p>Population weighted raster maps can present social audit findings in an accessible and compelling way, increasing the use of evidence by planners with limited numeracy skills or little time to look at evidence. Maps complement epidemiological analysis, but they are not a substitute. Much less do they substitute for rigorous epidemiological designs, like randomised controlled trials.</p

Drosophila S2 Cells Are Non-Permissive for Vaccinia Virus DNA Replication Following Entry via Low pH-Dependent Endocytosis and Early Transcription

Vaccinia virus (VACV), a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis

Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation

The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors.We thank Javier Salguero for help with animal experimentation and immunohistochemistry, Rocío Martín and Carolina Sánchez for technical assistance and Daniel Rubio for discussions on the project. This work was funded by Grants from the Spanish Ministry of Economy and Competitiviness and European Union (European Regional Development’s Funds, FEDER) (grant SAF2015-67485-R), and the Wellcome Trust (grant 051087/Z97/Z). M.B.R.-A. and A. Alejo were recipients of a Ramón y Cajal Contract from the Spanish Ministry of Science and Innovation