Präzision MRT-basierter Gelenkflächen- und Knorpeldickenanalysen im Kniegelenk bei Verwendung einer schnellen Wasseranregungs-Sequenz und eines semiautomatischen Segmentierungs-Algorithmus

The aim of this study was to analyse the precision of three-dimensional joint surface and cartilage thickness measurements in the knee, using a fast, high-resolution water-excitation sequence and a semiautomated segmentation algorithm. The knee joint of 8 healthy volunteers, aged 22 to 29 years, were examined at a resolution of 1.5 mm x 0.31 mm x 0.31 mm, with four sagittal data sets being acquired after repositioning the joint. After semiautomated segmentation with a B-spline Snake algorithm and 3D reconstruction of the patellar, femoral and tibial cartilages, the joint surface areas (triangulation), cartilage volume, and mean and maximum thickness (Euclidean distance transformation) were analysed, independently of the orientation of the sections. The precision (CV%) for the surface areas was 2.1 to 6.6%. The mean cartilage thickness and cartilage volume showed coefficients of 1.9 to 3.5% (except for the femoral condyles), the value for the medial femoral condyle being 9.1%, and for the lateral condyle 6.5%. For maximum thickness, coefficients of between 2.6 and 5.9% were found. In the present study we investigate for the first time the precision of MRI-based joint surface area measurements in the knee, and of cartilage thickness analyses in the femur. Using a selective water-excitation sequence, the acquisition time can be reduced by more than 50%. The poorer precision in the femoral condyles can be attributed to partial Volume effects that occur at the edges of the joint surfaces with a sagittal image protocol. Since MRI is non-invasive, it is highly suitable for examination of healthy subjects (generation of individual finite element models, analysis of functional adaptation to mechanical stimulation, measurement of cartilage deformation in vivo) and as a diagnostic tool for follow-up, indication for therapy, and objective evaluation of new therapeutic agents in osteoarthritis

Eine neue In-vivo-Technik zur dreidimensionalen Analyse der Translation der Femurkondylen und der Menisken unter dem Einfluß antagonistischer Muskelkräfte

The aim of our study was to develop a 3-D MR-based technique for the analysis of meniscal and femoral translations during flexion of the knee, and under the influence of antagonistic muscle forces in healthy subjects. In an open MR system, 5 knees were examined at 30 degrees and 90 degrees flexion using a T1-weighted 3-D gradient echo sequence. A force of 30 Newtons, first in the extending and then in the flexing direction, was applied to the distal lower leg. After three-dimensional reconstruction, the minimal distances between the centre of the tibial plateau and the posterior edge of the menisci and femoral condyles were determined. At 30 degrees flexion, the minimum distance for the meniscus was larger medially than laterally (23.2 +/- 1.8 mm vs. 16.2 +/- 3.3 mm), and this also applied to the condyles (25.1 +/- 1.5 vs. 19.0 +/- 3.0 mm). During flexion to 90 degrees, a posterior translation of 0.5 +/- 0.2 mm was observed for the lateral, and of 3.4 +/- 1.2 mm for the medial, meniscus. The condyles demonstrated a different posterior translation (lateral 2.2 +/- 0.56 mm; medial 1.8 +/- 1.9 mm). No obvious differences were found between extension and flexion muscle activity for the different positions of the knee. In the present study, a new 3-D technique is presented for the analysis of the femoral and meniscal translation at various positions of the knee, and under muscle activity. The results suggest different translation for the menisci and condyles

Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B

Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-α. We previously showed that human LITAF forms a complex with human STAT6B, which translocates into the nucleus to upregulate cytokine transcription. To dissect the molecular implications of this complex, a murine model was developed and interactions between mouse STAT6B (mSTAT6B) and mouse LITAF (mLITAF) were analyzed. Both mLITAF and mSTAT6B expression were MyD88- and TLR ligand-dependent. Furthermore, mLITAF was found to mediate LPS-induced CCL2 gene transcription with the cooperation of mSTAT6B leading to CCL2 protein expression. In LITAF-deficient mice, mLITAF-mediated CCL2 production in macrophages was significantly reduced compared to the wild-type control animals. Mice knockdown for mSTAT6B by 6BsiRNA1 tail vein injection resulted in a decrease in serum TNF-α and CCL2 production. mLITAF/mSTAT6B complex is proposed to play a role in LPS-induced CCL2 expression and possibly other cytokines

Insights into the Function of the CRM1 Cofactor RanBP3 from the Structure of Its Ran-Binding Domain

Proteins bearing a leucine-rich nuclear export signal (NES) are exported from the nucleus by the transport factor CRM1, which forms a cooperative ternary complex with the NES-bearing cargo and with the small GTPase Ran. CRM1-mediated export is regulated by RanBP3, a Ran-interacting nuclear protein. Unlike the related proteins RanBP1 and RanBP2, which promote disassembly of the export complex in the cytosol, RanBP3 acts as a CRM1 cofactor, enhancing NES export by stabilizing the export complex in the nucleus. RanBP3 also alters the cargo selectivity of CRM1, promoting recognition of the NES of HIV-1 Rev and of other cargos while deterring recognition of the import adaptor protein Snurportin1. Here we report the crystal structure of the Ran-binding domain (RBD) from RanBP3 and compare it to RBD structures from RanBP1 and RanBP2 in complex with Ran and CRM1. Differences among these structures suggest why RanBP3 binds Ran with unusually low affinity, how RanBP3 modulates the cargo selectivity of CRM1, and why RanBP3 promotes assembly rather than disassembly of the export complex. The comparison of RBD structures thus provides an insight into the functional diversity of Ran-binding proteins

Gas flows, star formation and galaxy evolution

In the first part of this article we show how observations of the chemical evolution of the Galaxy: G- and K-dwarf numbers as functions of metallicity, and abundances of the light elements, D, Li, Be and B, in both stars and the interstellar medium (ISM), lead to the conclusion that metal poor HI gas has been accreting to the Galactic disc during the whole of its lifetime, and is accreting today at a measurable rate, ~2 Msun per year across the full disc. Estimates of the local star formation rate (SFR) using methods based on stellar activity, support this picture. The best fits to all these data are for models where the accretion rate is constant, or slowly rising with epoch. We explain here how this conclusion, for a galaxy in a small bound group, is not in conflict with graphs such as the Madau plot, which show that the universal SFR has declined steadily from z=1 to the present day. We also show that a model in which disc galaxies in general evolve by accreting major clouds of low metallicity gas from their surroundings can explain many observations, notably that the SFR for whole galaxies tends to show obvious variability, and fractionally more for early than for late types, and yields lower dark to baryonic matter ratios for large disc galaxies than for dwarfs. In the second part of the article we use NGC 1530 as a template object, showing from Fabry-Perot observations of its Halpha emission how strong shear in this strongly barred galaxy acts to inhibit star formation, while compression acts to stimulate it.Comment: 20 pages, 10 figures, to be presented at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Africa, proceedings published by Kluwer, Eds. D.L. Block, K.C. Freeman, I. Puerari, & R. Groes

HIV infection of non-dividing cells: a divisive problem

Understanding how lentiviruses can infect terminally differentiated, non-dividing cells has proven a very complex and controversial problem. It is, however, a problem worth investigating, for it is central to HIV-1 transmission and AIDS pathogenesis. Here I shall attempt to summarise what is our current understanding for HIV-1 infection of non-dividing cells. In some cases I shall also attempt to make sense of controversies in the field and advance one or two modest proposals

Nucleo-cytoplasmic transport of proteins and RNA in plants

Merkle T. Nucleo-cytoplasmic transport of proteins and RNA in plants. Plant Cell Reports. 2011;30(2):153-176.Transport of macromolecules between the nucleus and the cytoplasm is an essential necessity in eukaryotic cells, since the nuclear envelope separates transcription from translation. In the past few years, an increasing number of components of the plant nuclear transport machinery have been characterised. This progress, although far from being completed, confirmed that the general characteristics of nuclear transport are conserved between plants and other organisms. However, plant-specific components were also identified. Interestingly, several mutants in genes encoding components of the plant nuclear transport machinery were investigated, revealing differential sensitivity of plant-specific pathways to impaired nuclear transport. These findings attracted attention towards plant-specific cargoes that are transported over the nuclear envelope, unravelling connections between nuclear transport and components of signalling and developmental pathways. The current state of research in plants is summarised in comparison to yeast and vertebrate systems, and special emphasis is given to plant nuclear transport mutants

Nucleo-cytoplasmic shuttling of Axin, a negative regulator of the Wnt-beta-catenin Pathway

Axin is a negative regulator of the Wnt pathway essential for down-regulation of beta-catenin. Axin has been considered so far as a cytoplasmic protein. Here we show that, although cytoplasmic at steady state, Axin shuttles in fact in and out of the nucleus; Axin accumulates in the nucleus of cells treated with leptomycin B, a specific inhibitor of the CRM1-mediated nuclear export pathway and is efficiently exported from Xenopus oocyte nuclei in a RanGTP- and CRM1-dependent manner. We have characterized the sequence requirement for export and identified two export domains, which do not contain classical nuclear export consensus sequences, and we show that Axin binds directly to the export factor CRM1 in the presence of RanGTP