Duodenal adipose tissue is associated with obesity in baboons (Papio sp) : a novel site of ectopic fat deposition in non-human primates

AimsEctopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.MethodsDuodenal tissues were collected from aged (21.21.3years, 19.53.1kg, n=39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated.Results Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 +/- 6.93%) and was correlated with AC (r=0.60, p<0.001), weight (r=0.38, p=0.02), leptin (r=0.63, p<0.001), adiponectin (r=-0.32, p<0.05), and triglyceride (r=0.41, p=0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 mu m(2), p=0.02).Conclusions Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition

Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study.

To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated. A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma

Current status of turbulent dynamo theory: From large-scale to small-scale dynamos

Several recent advances in turbulent dynamo theory are reviewed. High resolution simulations of small-scale and large-scale dynamo action in periodic domains are compared with each other and contrasted with similar results at low magnetic Prandtl numbers. It is argued that all the different cases show similarities at intermediate length scales. On the other hand, in the presence of helicity of the turbulence, power develops on large scales, which is not present in non-helical small-scale turbulent dynamos. At small length scales, differences occur in connection with the dissipation cutoff scales associated with the respective value of the magnetic Prandtl number. These differences are found to be independent of whether or not there is large-scale dynamo action. However, large-scale dynamos in homogeneous systems are shown to suffer from resistive slow-down even at intermediate length scales. The results from simulations are connected to mean field theory and its applications. Recent work on helicity fluxes to alleviate large-scale dynamo quenching, shear dynamos, nonlocal effects and magnetic structures from strong density stratification are highlighted. Several insights which arise from analytic considerations of small-scale dynamos are discussed.Comment: 36 pages, 11 figures, Spa. Sci. Rev., submitted to the special issue "Magnetism in the Universe" (ed. A. Balogh

A connectome and analysis of the adult Drosophila central brain

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain

A connectome and analysis of the adult Drosophila central brain

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved