Presence of the brown fat-specific mitochondrial uncoupling protein and iodothyronine 5'-deiodinase activity in subcutaneous adipose tissue of neonatal lambs

AbstractSubcutaneous adipose tissue of neonatal lambs has been examined for the presence of markers diagnostic of thermogenic brown fat. Uncoupling protein, uncoupling protein mRNA, and iodothyronine 5'-deiodinase activity were each detected in subcutaneous adipose tissue, as well as in the major internal fat depot (perirenal), of newborn lambs. These brown fat markers were not present, however, in adipose tissue of adult sheep. It is concluded that subcutaneous fat in newborn lambs is functionally ‘brown’, and similar to the internal fat; subcutaneous and internal adipose tissues follow a similar developmental path - from ‘brown’ to ‘white’

Assessing Anthocyanin Biosynthesis in Solanaceae as a Model Pathway for Secondary Metabolism

Solanaceae have played an important role in elucidating how flower color is specified by the flavonoid biosynthesis pathway (FBP), which produces anthocyanins and other secondary metabolites. With well-established reverse genetics tools and rich genomic resources, Solanaceae provide a robust framework to examine the diversification of this well-studied pathway over short evolutionary timescales and to evaluate the predictability of genetic perturbation on pathway flux. Genomes of eight Solanaceae species, nine related asterids, and four rosids were mined to evaluate variation in copy number of the suite of FBP enzymes involved in anthocyanin biosynthesis. Comparison of annotation sources indicated that the NCBI annotation pipeline generated more and longer FBP annotations on average than genome-specific annotation pipelines. The pattern of diversification of each enzyme among asterids was assessed by phylogenetic analysis, showing that the CHS superfamily encompasses a large paralogous family of ancient and recent duplicates, whereas other FBP enzymes have diversified via recent duplications in particular lineages. Heterologous expression of a pansy F3050H gene in tobacco changed flower color from pink to dark purple, demonstrating that anthocyanin production can be predictably modified using reverse genetics. These results suggest that the Solanaceae FBP could be an ideal system to model genotype-to-phenotype interactions for secondary metabolism

No association between intravenous fluid volume and endothelial glycocalyx shedding in patients undergoing resuscitation for sepsis in the emergency department

Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding—Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation—Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation—Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch—Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p \u3c 0.001) but not with Hyaluronan. Syn-1 and Syn-4 both correlated with VEGFR-1 (Rho 0.56 and 0.57 respectively, p \u3c 0.001) whereas Hyaluronan correlated with ET-1 (Rho 0.43, p \u3c 0.001) and Ang-2 (Rho 0.43, p \u3c 0.001). There was no correlation between Pro-ANP and any of the EG biomarkers. Distinct patterns of association between biomarkers of EG shedding and endothelial cell activation were observed among patients undergoing resuscitation for sepsis. No relationship between IV fluid volume and Pro-ANP or any of the other biomarkers was observed

Real-time reporting of baleen whale passive acoustic detections from ocean gliders

Author Posting. © Acoustical Society of America, 2013. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 134 (2013): 1814-1823, doi:10.1121/1.4816406.In the past decade, much progress has been made in real-time passive acoustic monitoring of marine mammal occurrence and distribution from autonomous platforms (e.g., gliders, floats, buoys), but current systems focus primarily on a single call type produced by a single species, often from a single location. A hardware and software system was developed to detect, classify, and report 14 call types produced by 4 species of baleen whales in real time from ocean gliders. During a 3-week deployment in the central Gulf of Maine in late November and early December 2012, two gliders reported over 25 000 acoustic detections attributed to fin, humpback, sei, and right whales. The overall false detection rate for individual calls was 14%, and for right, humpback, and fin whales, false predictions of occurrence during 15-min reporting periods were 5% or less. Transmitted pitch tracks—compact representations of sounds—allowed unambiguous identification of both humpback and fin whale song. Of the ten cases when whales were sighted during aerial or shipboard surveys and a glider was within 20 km of the sighting location, nine were accompanied by real-time acoustic detections of the same species by the glider within ±12 h of the sighting time.The Office of Naval Research funded this work, with additional support provided by the NOAA Fisheries Advanced Sampling Technologies Working Group via the Cooperative Institute for the North Atlantic Region

A Humanized Bone Niche Model Reveals Bone Tissue Preservation Upon Targeting Mitochondrial Complex I in Pseudo-Orthotopic Osteosarcoma

A cogent issue in cancer research is how to account for the effects of tumor microenvironment (TME) on the response to therapy, warranting the need to adopt adequate in vitro and in vivo models. This is particularly relevant in the development of strategies targeting cancer metabolism, as they will inevitably have systemic effects. For example, inhibition of mitochondrial complex I (CI), despite showing promising results as an anticancer approach, triggers TME-mediated survival mechanisms in subcutaneous osteosarcoma xenografts, a response that may vary according to whether the tumors are induced via subcutaneous injection or by intrabone orthotopic transplantation. Thus, with the aim to characterize the TME of CI-deficient tumors in a model that more faithfully represents osteosarcoma development, we set up a humanized bone niche ectopic graft. A prominent involvement of TME was revealed in CI-deficient tumors, characterized by the abundance of cancer associated fibroblasts, tumor associated macrophages and preservation of osteocytes and osteoblasts in the mineralized bone matrix. The pseudo-orthotopic approach allowed investigation of osteosarcoma progression in a bone-like microenvironment setting, without being invasive as the intrabone cell transplantation. Additionally, establishing osteosarcomas in a humanized bone niche model identified a peculiar association between targeting CI and bone tissue preservation

Chronic or recurrent Campylobacter enteritis in primary immunodeficiency: A UK national case-series and review of the literature

Campylobacter infection is an important diagnosis to consider in primary immunodeficiency patients with chronic or recurrent diarrhea, particularly in those with very low diagnostic immunoglobulin levels. Macrolides, aminoglycosides, and/or carbapenems are promising treatment options for this potentially debilitating condition