Molecular imaging: novel tools in visualizing rheumatoid arthritis

Molecular imaging is a rapidly emerging field in biomedical research, aiming at the visualization, characterization and quantification of molecular and cellular processes non-invasively within intact living organisms. To sense biological processes such as gene expression, angiogenesis, apoptosis or cell trafficking in vivo, imaging reporter agents that interact specifically with molecular targets and appropriate imaging systems are currently under development. In rheumatoid arthritis, these novel tools will be used to evaluate physiological and pathophysiological processes, to facilitate diagnosis and monitor therapeutic regimens, to enable reliable prognosis and to support the development of new therapies. In this review, we summarize the basic principles of molecular imaging, such as the development of molecular imaging agents, the actual capabilities of different imaging modalities and the most recent advances in molecular imaging, demonstrating the potential of this technology. With regard to their applicability in rheumatic diseases, we discuss potential molecular targets, current experimental approaches and the future prospects for molecular imaging in rheumatoid arthriti

Gene expression in cultured endometrium from women with different outcomes following IVF

Estradiol and progesterone are crucial for the acquisition of receptivity and the change in transcriptional activity of target genes in the implantation window. The aim of this study was to differentiate the regulation of genes in the endometrium of patients with recurrent implantation failure (IF) versus those who became pregnant after in vitro fertilization (IVF) treatment. Moreover, the effect of embryo-derived factors on endometrial transcriptional activity was studied. Nine women with known IVF outcome (IF, M, miscarriage, OP, ongoing pregnancy) and undergoing hysteroscopy with endometrial biopsy were enrolled. Biopsies were taken during the midluteal phase. After culture in the presence of embryo-conditioned IVF media, total RNA was extracted and submitted to reverse transcription, target cDNA synthesis, biotin labelling, fragmentation and hybridization using the Affymetrix Human Genome U133A 2.0 Chip. Differential expression of selected genes was re-analysed by quantitative PCR, in which the results were calculated as threshold cycle differences between the groups and normalized to Glyceraldehyde phosphate dehydrogenase and β-actin. Differences were seen for several genes from endometrial tissue between the IF and the pregnancy groups, and when comparing OP with M, 1875 up- and 1807 down-regulated genes were returned. Real-time PCR analysis confirmed up-regulation for somatostatin, PLAP-2, mucin 4 and CD163, and down-regulation of glycodelin, IL-24, CD69, leukaemia inhibitory factor and prolactin receptor between Op and M. When the different embryo-conditioned media were compared, no significant differential regulation could be demonstrated. Although microarray profiling may currently not be sensitive enough for studying the effects of embryo-derived factors on the endometrium, the observed differences in gene expression between M and OP suggest that it will become an interesting tool for the identification of fertility-relevant markers produced by the endometriu

Growth of Turtles During Continual Centrifugation

Juvenile Red Eared turtles (Pseudemys scripta elegans) were continuously centrifuged for as long as 9 weeks at 5 and 6 times the Earth\u27s gravity. On a carapace-length basis growth was 159±75% more at 5 G than under control conditions (1 G). These results were contrary to those with young mice at comparable fields in which the mice displayed a slower growth rate than their controls. The nature of the response appears to be dependent upon the feeding pattern

Extending land footprints towards characterizing sustainability of land use

The global trade of biomass-based products leads to an increasing regional decoupling of the area of production and consumption. Area-based land footprint calculations attribute the extents of land use required to prevailing national consumption patterns. Another report (Fischer et al., 2016) of the present study describes the methodology for the calculation of area-based footprints and presents results for Germany and the EU. Beyond area extents, additional information is needed to assess the sustainability of land use, requiring further analyses regarding environmental impacts and preservation of land quality and ecosystem services. This report discusses extensions of area-based land footprints with meaningful impact-oriented indicators for the assessment of the effects of different consumption patterns on the ecosystems and sustainability of land use. First, existing indicators for representing the environmental impacts of land use are introduced in the context of their linkages and complementarity to area-based land footprints. The report discusses the following key indicators, which were identified as particularly relevant during an export workshop: System indicators, which qualify the area-based footprints across globally very different potential land productivities,deforestation footprint, energy use in agriculture, and irrigation water use in agriculture classified by degree of water scarcity. We introduce the methods developed for the quantification of system indicators for cropland and grassland footprints and for the deforestation footprint, and present results for Germany and the EU

p53 missense but not truncation mutations are associated with low levels of p21CIP1/WAF1 mRNA expression in primary human sarcomas

Many growth-suppressing signals converge to control the levels of the CDK inhibitor p21CIP1/WAF1. Some human cancers exhibit low levels of expression of p21CIP1/WAF1and mutations in p53 have been implicated in this down-regulation. To evaluate whether the presence of p53 mutations was related to the in vivo expression of p21CIP1/WAF1 mRNA in sarcomas we measured the p21CIP1/WAF1 mRNA levels for a group of 71 primary bone and soft tissue tumours with known p53 status. As expected, most tumours with p53 mutations expressed low levels of p21CIP1/WAF1 mRNA. However, we identified a group of tumours with p53 gene mutations that exhibited normal or higher levels of p21CIP1/WAF1 mRNA. The p53 mutations in the latter group were not the common missense mutations in exons 4–9, but were predominantly nonsense mutations predicted to result in truncation of the p53 protein. The results of this study suggest that different types of p53 mutations can have different effects on the expression of downstream genes such as p21CIP1/WAF1 in human sarcomas. © 2001 Cancer Research Campaign http://www.bjcancer.co

Passive room conditioning using phase change materials—Demonstration of a long-term real size experiment

The thermal properties of lightweight buildings can be efficiently improved by using phase change materials (PCMs). The heat storage capacity of the building can be extended exactly at the desired temperature level, which leads to an enormous increase in residential comfort. This is shown in the present paper using the example of a prefabricated wooden house. The house was divided into two identical rooms. One of them was equipped with almost one ton of phase change material based on salt hydrates with a melting temperature of approx. 21°C. The material was encapsulated in 1-l Polyethylene containers and installed in two back-ventilated layers inside of the walls. The house was monitored for a period of 87 days in terms of temperatures, solar radiation and air velocity inside the PCM wall system. A considerable temperature buffering could be observed in the PCM room compared to the reference room. An overall reduction of the temperature fluctuations of 57% and a reduction of the day/night fluctuations of 62% compared to the reference room could be obtained. In addition, a prediction regarding the energy demand of such buildings is discussed on the basis of a simulation program. Thus, the annual cooling capacity can be reduced by 36.5% compared to the regular timber construction technique by introducing PCM. Furthermore, the good correlation of the simulation results with the experimental ones allows using the simulation as a tool to design a house with additional thermal storages

FcpB Is a Surface Filament Protein of the Endoflagellum Required for the Motility of the Spirochete Leptospira

International audienceThe spirochete endoflagellum is a unique motility apparatus among bacteria. Despite its critical importance for pathogenesis, the full composition of the flagellum remains to be determined. We have recently reported that FcpA is a novel flagellar protein and a major component of the sheath of the filament of the spirochete Leptospira. By screening a library of random transposon mutants in the spirochete Leptospira biflexa, we found a motility-deficient mutant harboring a disruption in a hypothetical gene of unknown function. Here, we show that this gene encodes a surface component of the endoflagellar filament and is required for typical hook- and spiral-shaped ends of the cell body, coiled structure of the endoflagella, and high velocity phenotype. We therefore named the gene fcpB for flagellar-coiling protein B. fcpB is conserved in all members of the Leptospira genus, but not present in other organisms including other spirochetes. Complementation of the fcpB− mutant restored the wild-type morphology and motility phenotypes. Immunoblotting with anti-FcpA and anti-FcpB antisera and cryo-electron microscopy of the filament indicated that FcpB assembled onto the surface of the sheath of the filament and mostly located on the outer (convex) side of the coiled filament. We provide evidence that FcpB, together with FcpA, are Leptospira-specific novel components of the sheath of the filament, key determinants of the coiled and asymmetric structure of the endoflagella and are essential for high velocity. Defining the components of the endoflagella and their functions in these atypical bacteria should greatly enhance our understanding of the mechanisms by which these bacteria produce motility