Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women

Background: Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.Methods: 308 postmenopausal women aged 48-76 were followed for 8.3 ± 0.3 years, with deaths related to cardiovascular disease, cancer, or other causes being recorded. From lumbar X-rays at baseline the number (NCD), size, morphology and distribution of aortic calcification lesions were scored and combined into one Morphological Atherosclerotic Calcification Distribution (MACD) index. The hazard ratio for mortality was calculated for the MACD and for three other commonly used predictors: the EU SCORE card, the Framingham Coronary Heart Disease Risk Score (Framingham score), and the gold standard Aortic Calcification Severity score (AC24) developed from the Framingham Heart Study cohorts.Results: All four scoring systems showed increasing age, smoking, and raised triglyceride levels were the main predictors of mortality after adjustment for all other metabolic and physical parameters. The SCORE card and the Framingham score resulted in a mortality hazard ratio increase per standard deviation (HR/SD) of 1.8 (1.51-2.13) and 2.6 (1.87-3.71), respectively. Of the morphological x-ray based measures, NCD revealed a HR/SD >2 adjusted for SCORE/Framingham. The MACD index scoring the distribution, size, morphology and number of lesions revealed the best predictive power for identification of patients at risk of mortality, with a hazard ratio of 15.6 (p < 0.001) for the 10% at greatest risk of death.Conclusions: This study shows that it is not just the extent of aortic calcification that predicts risk of mortality, but also the distribution, shape and size of calcified lesions. The MACD index may provide a more sensitive predictor of mortality from aortic calcification than the commonly used AC24 and SCORE/Framingham point card systems

The Glial Regenerative Response to Central Nervous System Injury Is Enabled by Pros-Notch and Pros-NFκB Feedback

Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces proliferation of enwrapping glia, leading to axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, and may reflect a common underlying genetic mechanism. Here, we show that injury to the Drosophila larval CNS induces glial proliferation, and we uncover a gene network controlling this response. It consists of the mutual maintenance between the cell cycle inhibitor Prospero (Pros) and the cell cycle activators Notch and NFκB. Together they maintain glia in the brink of dividing, they enable glial proliferation following injury, and subsequently they exert negative feedback on cell division restoring cell cycle arrest. Pros also promotes glial differentiation, resolving vacuolization, enabling debris clearance and axonal enwrapment. Disruption of this gene network prevents repair and induces tumourigenesis. Using wound area measurements across genotypes and time-lapse recordings we show that when glial proliferation and glial differentiation are abolished, both the size of the glial wound and neuropile vacuolization increase. When glial proliferation and differentiation are enabled, glial wound size decreases and injury-induced apoptosis and vacuolization are prevented. The uncovered gene network promotes regeneration of the glial lesion and neuropile repair. In the unharmed animal, it is most likely a homeostatic mechanism for structural robustness. This gene network may be of relevance to mammalian glia to promote repair upon CNS injury or disease

Tissue-specific study across the stem reveals the chemistry and transcriptome dynamics of birch bark.

Tree bark is a highly specialized array of tissues that plays important roles in plant protection and development. Bark tissues develop from two lateral meristems; the phellogen (cork cambium) produces the outermost stem-environment barrier called the periderm, while the vascular cambium contributes with phloem tissues. Although bark is diverse in terms of tissues, functions and species, it remains understudied at higher resolution. We dissected the stem of silver birch (Betula pendula) into eight major tissue types, and characterized these by a combined transcriptomics and metabolomics approach. We further analyzed the varying bark types within the Betulaceae family. The two meristems had a distinct contribution to the stem transcriptomic landscape. Furthermore, inter- and intraspecies analyses illustrated the unique molecular profile of the phellem. We identified multiple tissue-specific metabolic pathways, such as the mevalonate/betulin biosynthesis pathway, that displayed differential evolution within the Betulaceae. A detailed analysis of suberin and betulin biosynthesis pathways identified a set of underlying regulators and highlighted the important role of local, small-scale gene duplication events in the evolution of metabolic pathways. This work reveals the transcriptome and metabolic diversity among bark tissues and provides insights to its development and evolution, as well as its biotechnological applications.peerReviewe

The conservation and uniqueness of the caspase family in the basal chordate, amphioxus

<p>Abstract</p> <p>Background</p> <p>The caspase family, which plays a central role in apoptosis in metazoans, has undergone an expansion in amphioxus, increasing to 45 members through domain recombination and shuffling.</p> <p>Results</p> <p>In order to shed light on the conservation and uniqueness of this family in amphioxus, we cloned three representative caspase genes, designated as <it>bbtCaspase-8, bbtCaspase-1/2 </it>and <it>bbtCaspase3</it>-like, from the amphioxus <it>Branchiostoma belcheri tsingtauense</it>. We found that <it>bbtCaspase-8 </it>with conserved protein architecture is involved in the Fas-associated death domain-Caspase-8 mediated pro-apoptotic extrinsic pathway, while <it>bbtCaspase3</it>-like may mediate a nuclear apoptotic pathway in amphioxus. Also, <it>bbtCaspase-1/2 </it>can co-localize with <it>bbtFADD2 </it>in the nucleus, and be recruited to the cytoplasm by amphioxus apoptosis associated speck-like proteins containing a caspase recruitment domain, indicating that <it>bbtCaspase-1/2 </it>may serve as a switch between apoptosis and caspase-dependent innate immune response in invertebrates. Finally, amphioxus extrinsic apoptotic pathway related caspases played important roles in early embryogenesis.</p> <p>Conclusions</p> <p>Our study not only demonstrates the conservation of <it>bbtCaspase-8 </it>in apoptosis, but also reveals the unique features of several amphioxus caspases with novel domain architectures arose some 500 million years ago.</p

Association of Osteocalcin and Abdominal Aortic Calcification in Older Women: The Study of Osteoporotic Fractures

Osteocalcin (OC) is produced by osteoblasts and vascular smooth muscle cells. In animal models, serum OC levels are strongly correlated with vascular calcium content, however, the association of OC with vascular calcification in humans is uncertain. The Study of Osteoporotic Fractures (SOF) enrolled community-living women, age ≥65 years. The present study included a subsample of 363 randomly selected SOF participants. Serum total OC was measured by ELISA, and abdominal aortic calcification (AAC) was evaluated on lateral lumbar radiographs. We examined the cross-sectional association between serum OC and AAC. The mean serum OC level was 24 ± 11 ng/ml and AAC was present in 188 subjects (52%). We observed no association of OC and AAC in either unadjusted or adjusted analyses. For example, each standard deviation higher OC level was associated with an odds ratio (OR) for AAC prevalence (AAC score >0) near unity (OR = 1.06; 95% CI, 0.82–1.36) in models adjusted for CVD risk factors. Further adjustment for intact parathyroid hormone, bone-specific alkaline phosphatase, 25-hydroxyvitamin D, and hip and spine bone mineral density did not materially change the results (OR = 1.22; 95% CI, 0.86–1.75). Similarly, higher OC levels were not associated with severity of AAC (P = 0.87). In conclusion, among community-living older women, serum OC is not associated with AAC. These findings suggest that serum OC levels may more closely reflect bone formation than vascular calcification in humans

Transport poverty and fuel poverty in the UK: From analogy to comparison

The notion of ’fuel poverty’, referring to affordable warmth, underpins established research and policy agendas in the UK and has been extremely influential worldwide. In this context, British researchers, official policymaking bodies and NGOs have put forward the notion of ’transport poverty’, building on an implicit analogy between (recognised) fuel poverty and (neglected) transport affordability issues. However, the conceptual similarities and differences between ’fuel’ and ’transport’ poverty remain largely unaddressed in the UK. This paper systematically compares and contrasts the two concepts, examining critically the assumption of a simple equivalence between them. We illustrate similarities and differences under four headings: (i) negative consequences of lack of warmth and lack of access; (ii) drivers of fuel and transport poverty; (iii) definition and measurement; (iv) policy interventions. Our review suggests that there are important conceptual and practical differences between transport and domestic energy consumption, with crucial consequences for how affordability problems amongst households are to be conceptualised and addressed. In a context where transport and energy exhibit two parallel policy worlds, the analysis in the paper and these conclusions reinforce how and why these differences matter. As we embark on an ever closer union between our domestic energy and transport energy systems the importance of these contradictions will become increasingly evident and problematic. This work contributes to the long-term debate about how best to manage these issues in a radical energy transition that properly pays attention to issues of equity and affordability