Robust and Fast Whole Brain Mapping of the RF Transmit Field B1 at 7T

In-vivo whole brain mapping of the radio frequency transmit field B1+ is a key aspect of recent method developments in ultra high field MRI. We present an optimized method for fast and robust in-vivo whole-brain B1+ mapping at 7T. The method is based on the acquisition of stimulated and spin echo 3D EPI images and was originally developed at 3T. We further optimized the method for use at 7T. Our optimization significantly improved the robustness of the method against large B1+ deviations and off-resonance effects present at 7T. The mean accuracy and precision of the optimized method across the brain was high with a bias less than 2.6 percent unit (p.u.) and random error less than 0.7 p.u. respectively

A pilot Internet "Value of Health" Panel: recruitment, participation and compliance

Objectives To pilot using a panel of members of the public to provide preference data via the Internet Methods A stratified random sample of members of the general public was recruited and familiarised with the standard gamble procedure using an Internet based tool. Health states were perdiodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. Results A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. Conclusion It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field

Inactivation of the dnaK gene in Clostridium difficile 630 Δerm yields a temperature-sensitive phenotype and increases biofilm-forming ability

Abstract Clostridium difficile infection is a growing problem in healthcare settings worldwide and results in a considerable socioeconomic impact. New hypervirulent strains and acquisition of antibiotic resistance exacerbates pathogenesis; however, the survival strategy of C. difficile in the challenging gut environment still remains incompletely understood. We previously reported that clinically relevant heat-stress (37–41 °C) resulted in a classical heat-stress response with up-regulation of cellular chaperones. We used ClosTron to construct an insertional mutation in the dnaK gene of C. difficile 630 Δerm. The dnaK mutant exhibited temperature sensitivity, grew more slowly than C. difficile 630 Δerm and was less thermotolerant. Furthermore, the mutant was non-motile, had 4-fold lower expression of the fliC gene and lacked flagella on the cell surface. Mutant cells were some 50% longer than parental strain cells, and at optimal growth temperatures, they exhibited a 4-fold increase in the expression of class I chaperone genes including GroEL and GroES. Increased chaperone expression, in addition to the non-flagellated phenotype of the mutant, may account for the increased biofilm formation observed. Overall, the phenotype resulting from dnaK disruption is more akin to that observed in Escherichia coli dnaK mutants, rather than those in the Gram-positive model organism Bacillus subtilis

Hand sanitisers for reducing illness absences in primary school children in New Zealand: a cluster randomised controlled trial study protocol

<p>Abstract</p> <p>Background</p> <p>New Zealand has relatively high rates of morbidity and mortality from infectious disease compared with other OECD countries, with infectious disease being more prevalent in children compared with others in the population. Consequences of infectious disease in children may have significant economic and social impact beyond the direct effects of the disease on the health of the child; including absence from school, transmission of infectious disease to other pupils, staff, and family members, and time off work for parents/guardians. Reduction of the transmission of infectious disease between children at schools could be an effective way of reducing the community incidence of infectious disease. Alcohol based no-rinse hand sanitisers provide an alternative hand cleaning technology, for which there is some evidence that they may be effective in achieving this. However, very few studies have investigated the effectiveness of hand sanitisers, and importantly, the potential wider economic implications of this intervention have not been established.</p> <p>Aims</p> <p>The primary objective of this trial is to establish if the provision of hand sanitisers in primary schools in the South Island of New Zealand, in addition to an education session on hand hygiene, reduces the incidence rate of absence episodes due to illness in children. In addition, the trial will establish the cost-effectiveness and conduct a cost-benefit analysis of the intervention in this setting.</p> <p>Methods/Design</p> <p>A cluster randomised controlled trial will be undertaken to establish the effectiveness and cost-effectiveness of hand sanitisers. Sixty-eight primary schools will be recruited from three regions in the South Island of New Zealand. The schools will be randomised, within region, to receive hand sanitisers and an education session on hand hygiene, or an education session on hand hygiene alone. Fifty pupils from each school in years 1 to 6 (generally aged from 5 to 11 years) will be randomly selected for detailed follow-up about their illness absences, providing a total of 3400 pupils. In addition, absence information will be collected on all children from the school rolls. Investigators not involved in the running of the trial, outcome assessors, and the statistician will be blinded to the group allocation until the analysis is completed.</p> <p>Trial registration</p> <p>ACTRN12609000478213</p

L,L-Diaminopimelate Aminotransferase from Chlamydomonas reinhardtii: A Target for Algaecide Development

In some bacterial species and photosynthetic cohorts, including algae, the enzyme l,l-diaminopimelate aminotransferase (DapL) (E.C. 2.6.1.83) is involved in the anabolism of the essential amino acid L-lysine. DapL catalyzes the conversion of tetrahydrodipicolinate (THDPA) to l,l-diaminopimelate (l,l-DAP), in one step bypassing the DapD, DapC and DapE enzymatic reactions present in the acyl DAP pathways. Here we present an in vivo and in vitro characterization of the DapL ortholog from the alga Chlamydomonas reinhardtii (Cr-DapL). The in vivo analysis illustrated that the enzyme is able to functionally complement the E. coli dap auxotrophs and was essential for plant development in Arabidopsis. In vitro, the enzyme was able to inter-convert THDPA and l,l-DAP, showing strong substrate specificity. Cr-DapL was dimeric in both solution and when crystallized. The structure of Cr-DapL was solved in its apo form, showing an overall architecture of a α/β protein with each monomer in the dimer adopting a pyridoxal phosphate-dependent transferase-like fold in a V-shaped conformation. The active site comprises residues from both monomers in the dimer and shows some rearrangement when compared to the apo-DapL structure from Arabidopsis. Since animals do not possess the enzymatic machinery necessary for the de novo synthesis of the amino acid l-lysine, enzymes involved in this pathway are attractive targets for the development of antibiotics, herbicides and algaecides

Modelling the Protective Efficacy of Alternative Delivery Schedules for Intermittent Preventive Treatment of Malaria in Infants and Children

BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy. METHODS AND FINDINGS: A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone. CONCLUSION: Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria

Working Memory Training Using Mental Calculation Impacts Regional Gray Matter of the Frontal and Parietal Regions

Training working memory (WM) improves performance on untrained cognitive tasks and alters functional activity. However, WM training's effects on gray matter morphology and a wide range of cognitive tasks are still unknown. We investigated this issue using voxel-based morphometry (VBM), various psychological measures, such as non-trained WM tasks and a creativity task, and intensive adaptive training of WM using mental calculations (IATWMMC), all of which are typical WM tasks. IATWMMC was associated with reduced regional gray matter volume in the bilateral fronto-parietal regions and the left superior temporal gyrus. It improved verbal letter span and complex arithmetic ability, but deteriorated creativity. These results confirm the training-induced plasticity in psychological mechanisms and the plasticity of gray matter structures in regions that have been assumed to be under strong genetic control

Assessing the genetic variation of Ty-1 and Ty-3 alleles conferring resistance to Tomato Yellow Leaf Curl Virus in a broad tomato germplasm

The online version of this article (doi:10.1007/s11032-015-0329-y) contains supplementary material, which is available to authorized users.[EN] Tomato yellow leaf curl virus (TYLCV) hampers tomato production worldwide. Our previous studies have focussed on mapping and ultimately cloning of the TYLCV resistance genes Ty-1 and Ty-3. Both genes are derived from Solanum chilense and were shown to be allelic. They code for an RNA-dependent RNA polymerase (RDR) belonging to the RDR gamma type defined by a DFDGD catalytic domain. In this study, we first fine-mapped the TYLCV resistance in S. chilense LA1932, LA1960 and LA1971. Results showed that chromosomal intervals of the causal genes in these TYLCV-resistant accessions overlap and cover the region where Ty-1/Ty-3 is located. Further, virus-induced gene silencing was used to silence Ty-1/Ty-3 in tomato lines carrying TYLCV resistance introgressed from S. chilense LA1932, LA1938 and LA1971. Results showed that silencing Ty-1/Ty-3 compromised the resistance in lines derived from S. chilense LA1932 and LA1938. The LA1971-derived material remained resistant upon silencing Ty-1/Ty-3. Further, we studied the allelic variation of the Ty-1/Ty-3 gene by examining cDNA sequences from nine S. chilense-derived lines/accessions and more than 80 tomato cultivars, landraces and accessions of related wild species. The DFDGD catalytic domain of the Ty-1/Ty-3 gene is conserved among all tomato lines and species analysed. In addition, the 12 base pair insertion at the 5-prime part of the Ty-1/Ty-3 gene was found not to be specific for the TYLCV resistance allele. However, compared with the susceptible ty-1 allele, the Ty-1/Ty-3 allele is characterized by three specific amino acids shared by seven TYLCV-resistant S. chilense accessions or derived lines. Thus, Ty-1/Ty-3-specific markers can be developed based on these polymorphisms. Elevated transcript levels were observed for all tested S. chilense RDR alleles (both Ty-1 and ty-1 alleles), demonstrating that elevated expression level is not a good selection criterion for a functional Ty-1/Ty-3 allele.The infectious TYLCV clone was kindly provided by Professor Eduardo Rodriguez Bejarano (Universidad de Malaga). We thank Dick Lohuis for his help with agro-infiltrations, Marc Hendriks and Marjon Arens for RNA isolation and sequencing. This project was financed by the Centre for BioSystems Genomics (CBSG), which is part of the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (http://www.cbsg.nl). Olga Julian was granted a scholarship by Generalitat Valenciana. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Caro, M.; Verlaan, MG.; Julián Rodríguez, O.; Finkers, R.; Wolters, AA.; Hutton, S.; Scott, JW.... (2015). Assessing the genetic variation of Ty-1 and Ty-3 alleles conferring resistance to Tomato Yellow Leaf Curl Virus in a broad tomato germplasm. Molecular Breeding. 35. doi:10.1007/s11032-015-0329-yS13235Agrama H, Scott J (2006) Quantitative trait loci for tomato yellow leaf curl virus and tomato mottle virus resistance in tomato. J Am Soc Hortic Sci 131:267–272Anbinder I, Reuveni M, Azari R, Paran I, Nahon S, Shlomo H, Chen L, Lapidot M, Levin I (2009) Molecular dissection of tomato leaf curl virus resistance in tomato line TY172 derived from Solanum peruvianum. Theor Appl Genet 119:519–530Bai Y, Van der Hulst R, Huang C, Wei L, Stam P, Lindhout P (2004) Mapping Ol-4, a gene conferring resistance to Oidium neolycopersici and originating from Lycopersicon peruvianum LA2172, requires multi-allelic, single-locus markers. Theor Appl Genet 109:1215–1223Butterbach P, Verlaan MG, Dullemans A, Lohuis D, Visser RGF, Bai Y, Kormelink R (2014) The TYLCV Resistance Gene Ty-1 confers resistance in tomato through enhanced transcriptional gene silencing. PNAS 111:12942–12947Cohen S, Lapidot M (2007) Appearance and expansion of TYLCV: a historical point of view. In: Czosnek H (ed) Tomato yellow leaf curl virus disease. Springer, The Netherlands, pp 3–12Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, Handsaker RE, Lunter G, Marth GT, Sherry ST, McVean G, Durbin R, Group GPA (2011) The variant call format and VCFtools. Bioinformatics 27:2156–2158Fauquet CM, Briddon RW, Brown JK, Moriones E, Stanley J, Zerbini M, Zhou X (2008) Geminivirus strain demarcation and nomenclature. Arch Virol 153:783–821Friedmann M, Lapidot M, Cohen S, Pilowsky M (1998) A novel source of resistance to Tomato yellow leaf curl virus exhibiting a symptomless reaction to viral infection. J Am Soc Hortic Sci 123:1004–1007Hanson PM, Green SK, Kuo G (2006) Ty-2, a gene on chromosome 11 conditioning geminivirus resistance in tomato. Tomato Genet Coop Rep 56:17–18Hutton SF, Scott JW (2013) Fine-mapping and cloning of Ty-1 and Ty-3; and mapping of a new TYLCV resistance locus, “Ty-6”. In: Tomato breeders round table proceedings 2013, Chiang Mai, ThailandHutton SF, Scott JW, Schuster DJ (2012) Recessive resistance to tomato yellow leaf curl virus from the tomato cultivar tyking is located in the same region as Ty-5 on chromosome 4. HortScience 47:324–327Ji Y, Schuster DJ, Scott JW (2007) Ty-3, a begomovirus resistance locus near the Tomato yellow leaf curl virus resistance locus Ty-1 on chromosome 6 of tomato. Mol Breeding 20:271–284Ji Y, Scott JW, Schuster DJ, Maxwell DP (2009) Molecular mapping of Ty-4, a new tomato yellow leaf curl virus resistance locus on chromosome 3 of tomato. J Am Soc Hortic Sci 134:281–288Levin I, Karniel U, Fogel D, Reuveni M, Gelbart D, Evenor D, Chen L, Nahon S, Shlomo H, Machbosh Z, Lapidot M (2013) Cloning and analysis of the tomato yellow leaf curl virus resistance gene Ty-5. In: Tomato breeders round table proceedings 2013, Chiang Mai, ThailandLi H, Durbin R (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25:1754–1760Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R (2009) The sequence alignment/map format and SAMtools. The sequence alignment/map format and SAMtools. Bioinformatics 25:2078–2079Mejía L, Teni RE, Vidavski F, Czosnek H, Lapidot M, Nakhla MK, Maxwell DP (2005) Evaluation of tomato germplasm and selection of breeding lines for resistance to begomoviruses in Guatemala. In: Momol MT, Ji P, Jones JB (eds) Proceedings 1st international symposium on tomato diseases. Acta Horticult 695:251–256Menda N, Strickler SR, Edwards JD, Bombarely A, Dunham DM, Martin GB, Mejia L, Hutton SF, Havey MJ, Maxwell DP, Mueller LA (2014) Analysis of wild-species introgressions in tomato inbreds uncovers ancestral origins. BMC Plant Biol 14(1):287Pérez de Castro A, Díez MJ, Nuez F (2007) Inheritance of Tomato yellow leaf curl virus resistance derived from Solanum pimpinellifolium UPV16991. Plant Dis 91:879–885Pérez de Castro A, Julián O, Díez M (2013) Genetic control and mapping of Solanum chilense LA1932, LA1960 and LA1971-derived resistance to tomato yellow leaf curl disease. Euphytica 190:203–214Pico B, Ferriol M, Diez MJ, Nuez F (1999) Developing tomato breeding lines resistant to tomato yellow leaf curl virus. Plant Breeding 118:537–542Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP (2011) Integrative genomics viewer. Nature. Biotech 29:24–26Sahu PP, Puranik S, Khan M, Prasad M (2012) Recent advances in tomato functional genomics: utilization of VIGS. Protoplasma 249(4):1017–1027Scott JW, Stevens MR, Barten JHM, Thome CR, Polston JE, Schuster DJ, Serra CA (1996) Introgression of resistance to whitefly-transmitted geminiviruses from Lycopersicon chilense to tomato. In: Gerling D, Mayer RT (eds) Bemisia 1995; taxonomy, biology, damage control, and management. Intercept Press, Andover, pp 357–367Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739The 100 Tomato Genome Sequencing Consortium (2014) Exploring genetic variation in the tomato (Solanum section Lycopersicon) clade by whole-genome sequencing. Plant J 80:136–148The Tomato Genome Consortium (2012) The tomato genome sequence provides insights into fleshy fruit evolution. Nature 485:635–641Vanitharani R, Chellappan P, Pita JS, Fauquet CM (2004) Differential roles of AC2 and AC4 of cassava geminiviruses in mediating synergism and suppression of posttranscriptional gene silencing. J Virol 78:9487–9498Verlaan MG, Szinay D, Hutton SF, de Jong H, Kormelink R, Visser RGF, Scott JW, Bai Y (2011) Chromosomal rearrangements between tomato and Solanum chilense hamper mapping and breeding of the TYLCV resistance gene Ty-1. Plant J 68:1093–1103Verlaan MG, Hutton SF, Ibrahem RM, Kormelink R, Visser RGF, Scott JW, Edwards JD, Bai Y (2013) The tomato yellow leaf curl virus resistance genes Ty-1 and Ty-3 are allelic and code for DFDGD-class RNA-dependent RNA polymerases. PLoS Genet 9(3):e1003399. doi: 10.1371/journal.pgen.1003399Vidavski F (2007) Exploitation of resistance genes found in wild tomato species to produce resistant cultivars; Pile up of Resistant Genes. In: Czosnek H (ed) Tomato yellow leaf curl virus disease. Springer, Netherlands, pp 363–372Willmann MR, Endres MW, Cook RT, Gregory BD (2011) The functions of RNA-dependent RNA polymerases in arabidopsis. In: The Arabidopsis Book, e0146Yang X, Caro M, Hutton SF, Scott JW, Guo Y, Wang X, Rashid MH, Szinay D, de Jong H, Visser RGF, Bai Y, Du Y (2014) Fine mapping of the tomato yellow leaf curl virus resistance gene Ty-2 on chromosome 11 of tomato. Mol Breeding 34:749–760Zamir D, Ekstein Michelson I, Zakay Y, Navot N, Zeidan M, Sarfatti M, Eshed Y, Harel E, Pleban T, van Oss H (1994) Mapping and introgression of a tomato yellow leaf curl virus tolerance gene, Ty-1. Theor Appl Genet 88:141–14