Creation of an Age-Adjusted, Dual-Energy X-ray Absorptiometry-Derived Trabecular Bone Score Curve for the Lumbar Spine in Non-Hispanic US White Women.

The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone microarchitecture texture extracted from anteroposterior dual-energy X-ray absorptiometry images of the spine. Previous studies have documented the ability of TBS of the spine to differentiate between women with and without fractures among age- and areal bone mineral density (aBMD)-matched controls, as well as to predict future fractures. In this cross-sectional analysis of data collected from 3 geographically dispersed facilities in the United States, we investigated age-related changes in the microarchitecture of lumbar vertebrae as assessed by TBS in a cohort of non-Hispanic US white American women. All subjects were 30 yr of age and older and had an L1-L4aBMDZ-score within ±2 SD of the population mean. Individuals were excluded if they had fractures, were on any osteoporosis treatment, or had any illness that would be expected to impact bone metabolism. All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE-Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1-L4 but also for all other possible vertebral combinations. To validate the cohort, a comparison between the aBMD normative data of our cohort and US non-Hispanic white Lunar data provided by the manufacturer was performed. A database of 619 non-Hispanic US white women, ages 30-90 yr, was created. aBMD normative data obtained from this cohort were not statistically different from the non-Hispanic US white Lunar normative data provided by the manufacturer (p = 0.30). This outcome thereby indirectly validates our cohort. TBS values at L1-L4 were weakly inversely correlated with body mass index (r = -0.17) and weight (r = -0.16) and not correlated with height. TBS values for all lumbar vertebral combinations decreased significantly with age. There was a linear decrease of 16.0% (-2.47 T-score) in TBS at L1-L4 between 45 and 90 yr of age (vs. -2.34 for aBMD). Microarchitectural loss rate increased after age 65 by 50% (-0.004 to -0.006). Similar results were obtained for other combinations of lumbar vertebra. TBS, an index of bone microarchitectural texture, decreases with advancing age in non-Hispanic US white women. Little change in TBS is observed between ages 30 and 45. Thereafter, a progressive decrease is observed with advancing age. The changes we observed in these American women are similar to that previously reported for a French population of white women (r(2) > 0.99). This reference database will facilitate the use of TBS to assess bone microarchitectural deterioration in clinical practice.

Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes.

The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigations, the major target genes of CIITA remain those implicated in the presentation of antigenic peptides by MHCII molecules. Although other putative target genes have been reported, the contribution of CIITA to their expression remains indirect, controversial or comparatively minor relative to its decisive role as a regulator of MHCII and related genes. Second, the most important parameter dictating MHCII expression is by far the expression pattern of the gene encoding CIITA (MHC2TA). The vast majority of signals that activate or repress MHCII expression under physiological and pathological situations converge on one or more of the three alternative promoters that drive transcription of the MHC2TA gene. In short, with respect to its specificity and its exquisitely controlled pattern of expression, CIITA is by a long stretch the single most important transcription factor for the regulation of genes required for MHCII-restricted antigen-presentation.

Reducing the learning curve for the treatment of morphoeic (sclerosing) basal cell carcinoma of the face.

The treatment of morphoeic (or sclerosing) basal cell carcinoma (mBCC) of the face is associated with high rates of incomplete excision and recurrence. A principal risk factor for incomplete resection is the grade of surgeon. We did a prospective, randomised study of 40 consecutive patients with mBCC of the face. The extent of the tumour was assessed under standard conditions by consultant surgeons and compared with assessments by resident surgeons with the help of the Varioscope, a combination of microscope and loupe glasses with strong illumination and a maximal magnification of 7x. The data from a former retrospective study of all excisions of mBCC of the face during a five-year period at the hospital served as control. Residents with the support of the Varioscope achieved a rate of incomplete excisions similar to that of consultants under standard conditions. There was a significant reduction of the rate of incomplete resections by resident surgeons thanks to high magnification and good lighting (p=0.02). High magnification and good lighting were useful in learning how to recognise skin changes associated with mBCC of the face and achieving a low rate of incomplete excisions.

Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization.

Efficient priming of adaptive immunity depends on danger signals provided by innate immune pathways. As an example, inflammasome-mediated activation of caspase-1 and IL-1beta is crucial for the development of reactive T cells targeting sensitizers like dinitrofluorobenzene (DNFB). Surprisingly, DNFB and dinitrothiocyanobenzene provide cross-reactive Ags yet drive opposing, sensitizing vs tolerizing, T cell responses. In this study, we show that, in mice, inflammasome-signaling levels can be modulated to turn dinitrothiocyanobenzene into a sensitizer and DNFB into a tolerizer, and that it correlates with the IL-6 and IL-12 secretion levels, affecting Th1, Th17, and regulatory T cell development. Hence, our data provide the first evidence that the inflammasome can define the type of adaptive immune response elicited by an Ag, and hint at new strategies to modulate T cell responses in vivo.

Constraints on the upper Permian to upper Triassic marine carbon isotope curve : case studies from the Tethys

Secular variations of the seawater carbon isotopic composition provide evidence for paleoceanographic and paleoclimatic changes and may serve for chemiostratigraphic correlations. The present study aimed to improve the current knowledge on the Upper Permian and Triassic segment of the Phanerozoic marine carbon isotope curve, whose Triassic part was poorly constrained by previous studies. Profiles of inorganic carbon isotopes are provided for sections from Himalaya (Salt Range, Kashmir, Spiti and Nepal), Oman and North Dobrogea (Romania) on the basis of whole-rock carbonate analysis. The data acquired, together with a literature compilation confirmed that most of the Upper Permian is characterized by high δ13C values (averaging +40/00) but failed to detect a positive excursion as suggested by recent compilations. In the light of these observations, the large drop in δ13C values associated with the end-Permian mass extinction appears to be driven by a sudden transfer of previously stocked 13C depleted carbon, rather than by the overturn of a Late Permian stratified ocean. The Triassic data-set outlines significant secular variations. The best documented is a carbon isotope positive excursion just across the Lower-Middle Triassic boundary, globally developed since it was detected in various paleogeographic settings. It is interpreted to reflect variations in surface ocean chemistry, possibly related to increased primary productivity, at times when the biotic recovery after the end-Permian mass-extinction began to accelerate significantly and when a sharp rise in seawater δ34S values occurred globally. Strontium isotope data obtained from well preserved biogenic phosphates allow a refinement of the Middle Triassic segment of the seawater strontium isotope curve and show a major inflexion point of the seawater strontium isotope curve also near the Lower Triassic - Middle Triassic boundary. These facts suggest that the transition from the Early to the Middle Triassic was a time of revolutionary global change which represented an important step in the evolution of Mesozoic marine environments. A tentative carbon isotope curve for the Upper Permian to Upper Triassic time interval is proposed. Its major features are: ? high but constant δ13C values during the Late Permian ? a sharp drop in δ13C values in the latest Permian ? subsequent recovery of δ13C values ? a short-lived positive excursion across the Early-Middle Triassic boundary ? a gradual rise in δ13C values starting in the Late Ladinian or in the Early Carnian It is foreseen that these fluctuations of the carbon isotope curve may serve as chronostratigraphic markers and further assist in the correlation of Permian and Triassic carbonate deposits.

Membrane and walls: who is master, who is servant?

Specialised plant cell types often locally modify their cell walls as part of a developmental program, as do cells that are challenged by particular environmental conditions. Modifications can include deposition of secondary cellulose, callose, cutin, suberin or lignin. Although the biosyntheses of cell wall components are more and more understood, little is known about the mechanisms that control localised deposition of wall materials. During metaxylem vessel differentiation, site-specific cell wall deposition is locally prevented by the microtubule depolymerising protein MIDD1, which disassembles the cytoskeleton and precludes the cellulose synthase complex from depositing cellulose. As a result, metaxylem vessel secondary cell wall appears pitted. How MIDD1 is tethered at the plasma membrane and how other cell wall polymers are locally deposited remain elusive. Casparian strips in the root endodermis represent a further example of local cell wall deposition. The recent discovery of the Casparian Strip membrane domain Proteins (CASPs), which are located at the plasma membrane and are important for the site-specific deposition of lignin during Casparian strip development, establishes the root endodermis as an attractive model system to study the mechanisms of localised cell wall modifications. How secondary modifications are modulated and monitored during development or in response to environmental changes is another question that still misses a complete picture.

Duplication and concerted evolution in a master sex determiner under balancing selection.

The transformer (tra) gene is a key regulator in the signalling hierarchy controlling all aspects of somatic sexual differentiation in Drosophila and other insects. Here, we show that six of the seven sequenced ants have two copies of tra. Surprisingly, the two paralogues are always more similar within species than among species. Comparative sequence analyses indicate that this pattern is owing to the ongoing concerted evolution after an ancestral duplication rather than independent duplications in each of the six species. In particular, there was strong support for inter-locus recombination between the paralogues of the ant Atta cephalotes. In the five species where the location of paralogues is known, they are adjacent to each other in four cases and separated by only few genes in the fifth case. Because there have been extensive genomic rearrangements in these lineages, this suggests selection acting to conserve their synteny. In three species, we also find a signature of positive selection in one of the paralogues. In three bee species where information is available, the tra gene is also duplicated, the copies are adjacent and in at least one species there was recombination between paralogues. These results suggest that concerted evolution plays an adaptive role in the evolution of this gene family.

Illustrating Yoga: from the master to the book

In dieser Auseinandersetzung mit Visualität stellen die Autorinnen und Autoren des Bandes die faszinierende Welt des Bildes an der Schnittstelle zwischen Religion und Kultur vor. Zunächst werden hermeneutische Zugänge zu Visualität erkundet, dann folgen Studien zum Blick und dessen Regulierung innerhalb religiöser Traditionen, schliesslich werden die Vielfalt visueller Medien und deren spezifische Wechselwirkungen mit Religion untersucht. Das Buch gibt mit seiner breiten Palette internationaler und interdisziplinärer Beiträge Einblick in die visuelle Welt religiöser Traditionen und leistet einen Beitrag zu einer spezifisch religionswissenschaftlichen Visualitätsforschung.

Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women.

Age-related changes in lumbar vertebral microarchitecture are evaluated, as assessed by trabecular bone score (TBS), in a cohort of 5,942 French women. The magnitude of TBS decline between 45 and 85 years of age is piecewise linear in the spine and averaged 14.5 %. TBS decline rate increases after 65 years by 50 %. INTRODUCTION: This study aimed to evaluate age-related changes in lumbar vertebral microarchitecture, as assessed by TBS, in a cohort of French women aged 45-85 years. METHODS: An all-comers cohort of French Caucasian women was selected from two clinical centers. Data obtained from these centers were cross-calibrated for TBS and bone mineral density (BMD). BMD and TBS were evaluated at L1-L4 and for all lumbar vertebrae combined using GE-Lunar Prodigy densitometer images. Weight, height, and body mass index (BMI) also were determined. To validate our all-comers cohort, the BMD normative data of our cohort and French Prodigy data were compared. RESULTS: A cohort of 5,942 French women aged 45 to 85 years was created. Dual-energy X-ray absorptiometry normative data obtained for BMD from this cohort were not significantly different from French prodigy normative data (p = 0.15). TBS values at L1-L4 were poorly correlated with BMI (r = -0.17) and weight (r = -0.14) and not correlated with height. TBS values obtained for all lumbar vertebra combined (L1, L2, L3, L4) decreased with age. The magnitude of TBS decline at L1-L4 between 45 and 85 years of age was piecewise linear in the spine and averaged 14.5 %, but this rate increased after 65 years by 50 %. Similar results were obtained for other region of interest in the lumbar spine. As opposed to BMD, TBS was not affected by spinal osteoarthrosis. CONCLUSION: The age-specific reference curve for TBS generated here could therefore be used to help clinicians to improve osteoporosis patient management and to monitor microarchitectural changes related to treatment or other diseases in routine clinical practice.