Abnormal molecular signatures of inflammation, energy metabolism, and vesicle biology in human Huntington disease peripheral tissues

BACKGROUND: A major challenge in neurodegenerative diseases concerns identifying biological disease signatures that track with disease progression or respond to an intervention. Several clinical trials in Huntington disease (HD), an inherited, progressive neurodegenerative disease, are currently ongoing. Therefore, we examine whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in HD patients. RESULTS: We generate large, high-quality human datasets from skeletal muscle, skin and adipose tissue to probe molecular changes in human premanifest and early manifest HD patients—those most likely involved in clinical trials. The analysis of the transcriptomics and proteomics data shows robust, stage-dependent dysregulation. Gene ontology analysis confirms the involvement of inflammation and energy metabolism in peripheral HD pathogenesis. Furthermore, we observe changes in the homeostasis of extracellular vesicles, where we find consistent changes of genes and proteins involved in this process. In-depth single nucleotide polymorphism data across the HTT gene are derived from the generated primary cell lines. CONCLUSIONS: Our ‘omics data document the involvement of inflammation, energy metabolism, and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials. The generated data, complemented by the primary cell lines established from peripheral tissues, and a large panel of iPSC lines that can serve as human models of HD are a valuable and unique resource to advance the current understanding of molecular mechanisms driving HD pathogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02752-5

A Decade of Volcanic Observations from Aura and the A-Train

Aura observations have made many seminal contributions to volcanology. Prior to the Aura launch, satellite observations of volcanic degassing (e.g., from TOMS) were mostly restricted to large eruptions. However, the vast majority of volcanic gases are released during quiescent 'passive' degassing between eruptions. The improved sensitivity of Aura OMI permitted the first daily, space-borne measurements of passive volcanic SO2 degassing, providing improved constraints on the source locations and magnitude of global SO2 emissions for input to atmospheric chemistry and climate models. As a result of this unique sensitivity to volcanic activity, OMI data were also the first satellite SO2 measurements to be routinely used for volcano monitoring at several volcano observatories worldwide. Furthermore, the Aura OMI SO2 data also offer unprecedented sensitivity to volcanic clouds in the UTLS, elucidating the transport, fate and lifetime of volcanic SO2 and providing critical input to aviation hazard mitigation efforts. Another major advance has been the improved vertical resolution of volcanic clouds made possible by synergy between Aura and other A-Train instruments (e.g., AIRS, CALIPSO, CloudSat), advanced UV SO2 altitude retrievals, and inverse trajectory modeling of detailed SO2 cloud maps. This altitude information is crucial for climate models and aviation hazards. We will review some of the highlights of a decade of Aura observations of volcanic activity and look ahead to the future of volcanic observations from space

Fiction Fix 10

https://digitalcommons.unf.edu/fiction_fix/1002/thumbnail.jp

A citizen science approach: A detailed ecological assessment of subtropical reefs at point lookout, Australia

Subtropical reefs provide an important habitat for flora and fauna, and proper monitoring is required for conservation. Monitoring these exposed and submerged reefs is challenging and available resources are limited. Citizen science is increasing in momentum, as an applied research tool and in the variety of monitoring approaches adopted. This paper aims to demonstrate an ecological assessment and mapping approach that incorporates both top-down (volunteer marine scientists) and bottom-up (divers/community) engagement aspects of citizen science, applied at a subtropical reef at Point Lookout, Southeast Queensland, Australia. Marine scientists trained fifty citizen scientists in survey techniques that included mapping of habitat features, recording of substrate, fish and invertebrate composition, and quantifying impacts (e.g., occurrence of substrate damage, presence of litter). In 2014 these volunteers conducted four seasonal surveys along semi-permanent transects, at five sites, across three reefs. The project presented is a model on how citizen science can be conducted in a marine environment through collaboration of volunteer researchers, non-researchers and local marine authorities. Significant differences in coral and algal cover were observed among the three sites, while fluctuations in algal cover were also observed seasonally. Differences in fish assemblages were apparent among sites and seasons, with subtropical fish groups observed more commonly in colder seasons. The least physical damage occurred in the most exposed sites (Flat Rock) within the highly protected marine park zones. The broad range of data collected through this top-down/bottomup approach to citizen science exemplifies the projects' value and application for identifying ecosystem trends or patterns. The results of the project support natural resource and marine park management, providing a valuable contribution to existing scientific knowledge and the conservation of local reefs

PGH1, the Precursor for the Anti-Inflammatory Prostaglandins of the 1-series, Is a Potent Activator of the Pro-Inflammatory Receptor CRTH2/DP2

Prostaglandin H1 (PGH1) is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as “anti-inflammatory”. Herein we present evidence that PGH1 is a potent activator of the pro-inflammatory PGD2 receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca2+ flux studies reveal that PGH1 activates CRTH2 as PGH2, PGD2 or PGD1 do. The PGH1 precursor DGLA and the other PGH1 metabolites did not display such effect. PGH1 specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. Physiological relevance of CRTH2 ligation by PGH1 is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH1 mediates migration of and Ca2+ flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089. Together, our results identify PGH1 as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

PLASMA ELECTROPHORETIC PROFILES AND HEMOGLOBIN BINDING PROTEIN REFERENCE INTERVALS IN THE EASTERN BOX TURTLE ( TERRAPENE CAROLINA CAROLINA

Evaluation of plasma electrophoretic profiles and acute phase protein concentrations may play a valuable role in health assessment of reptiles; however, little is known about reference intervals in free-ranging eastern box turtles (Terrapene carolina carolina). The purpose of this study was to establish reference intervals of protein electrophoretic profiles and hemoglobin binding protein ([HBP] as determined by a haptoglobin assay) in free-ranging eastern box turtles and to assess any possible correlations between varying age class (adults vs. juvenile), sex (male, female, or unknown), season (spring, summer, or fall), or location (Tennessee vs. Illinois). Blood samples were obtained from 324 eastern box turtles from 2010 to 2012 at three sites in Illinois and one site in Tennessee, USA. Significant differences were observed with total protein (sex, season, state, Illinois location), albumin (age class, season, state, Illinois location), α-1 globulins (sex, season, Illinois location), α-2 globulins (sex, season, state, Illinois location), β globulins (age class, sex, season, state, Illinois location), γ globulins (sex, season state, Illinois location), and hemoglobin binding protein (age class, sex, state, Illinois location). The use of electrophoretic profiles and acute phase proteins is a relatively new concept in reptilian medicine, and this study allowed for establishment of references intervals in the eastern box turtle and emphasized differences that occured based on age, sex, season, and location. Future research in this area can now build on these data to determine changes in population health over time or alterations due to specific environmental or disease threats

SERUM ACUTE-PHASE PROTEINS IN BOTTLENOSE DOLPHINS ( TURSIOPS TRUNCATUS ) AND CORRELATION WITH COMMONLY UTILIZED INFLAMMATORY INDICES

Acute-phase proteins (APP) are the foundation to the innate immune response and valuable biomarkers that increase with inflammation, infection, neoplasia, stress, and trauma. Little is known about the acute-phase response in cetaceans and if these proteins can be used for health monitoring in individuals and free-ranging populations. The purpose of this study was to characterize serum concentrations of haptoglobin (Hp) and serum amyloid A (SAA), as well as electrophoretic profiles of common bottlenose dolphins ( ) in free-ranging ( = 33) and professional care ( = 27) settings. Results were correlated to commonly utilized inflammatory indices including erythrocyte sedimentation rate (ESR), fibrinogen, total white blood cell count (WBC), and absolute neutrophil count. SAA levels, measured with a dolphin-specific enzyme linked immunosorbent assay (ELISA), were significantly higher ( = 0.05) in free-ranging dolphins (mean = 4.26; SE = 1.12) when compared with those under professional care (mean = 1.82; SE = 0.45). For dolphins under professional care, a statistically significant correlation was identified between ESR and Hp ( < 0.001; = 0.69), ESR and SAA ( < 0.001; = 0.67), fibrinogen and Hp ( = 0.001; = 0.58), and fibrinogen and SAA ( = 0.002; = 0.56). In addition, there was a significant correlation between WBC and SAA ( = 0.01; = 0.38) and absolute neutrophil count and SAA ( = 0.04; = 0.32). There were no significant correlations between study variables observed in free-ranging dolphins. The variable correlation of APPs with commonly utilized inflammatory indices demonstrates that these proteins are independent measures of inflammation with unique sensitivity, specificity, and timeline of expression. The results of this study contribute to improved health monitoring of dolphins and have the potential to assist in identification of compromised health