Proteomic Analysis of Single Hairs.

Hair is a ubiquitous and robust mammalian tissue with biological, clinical, forensic, social, and economic significance. The hair shaft proteome reflects both structural proteins, dominated by cuticular intermediate filament keratins and associated proteins, and proteins involved in the final cellular processes of terminally differentiating corneocytes prior to cornification. These distinct biological processes involve cell maintenance, biosynthesis, senescence, and xenobiotic response.

Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study.

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of () following RBC transfusion in dogs with atraumatic hemorrhage.

PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective.

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth.

Modelling Lipid-Coated Microbubbles in Focused Ultrasound Applications at Subresonance Frequencies.

We present a computational study of the behaviour of a lipid-coated SonoVue microbubble with initial radius 1 µm ≤ R ≤ 2 µm, excited at frequencies (200-1500 kHz) significantly below the linear resonance frequency and pressure amplitudes of up to 1500 kPa-an excitation regime used in many applications of focused ultrasound. The bubble dynamics are simulated using the Rayleigh-Plesset equation and the Gilmore equation, in conjunction with the Marmottant model for the lipid monolayer coating. Also, a new continuously differentiable variant of the Marmottant model is introduced.

Factors driving the compositional diversity of Apis mellifera bee venom from a Corymbia calophylla (marri) ecosystem, Southwestern Australia.

Bee venom (BV) is the most valuable product harvested from honeybees ($30 - $300 USD per gram) but marginally produced in apiculture. Though widely studied and used in alternative medicine, recent efforts in BV research have focused on its therapeutic and cosmetic applications, for the treatment of degenerative and infectious diseases. The protein and peptide composition of BV is integral to its bioactivity, yet little research has investigated the ecological factors influencing the qualitative and quantitative variations in the BV composition.

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging by Freeze-Spot Deposition of the Matrix.

Imaging mass spectrometry has emerged as a powerful metabolite measurement approach to capture the spatial dimension of metabolite distribution in a biological sample. In matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), deposition of the chemical-matrix onto the sample serves to simultaneously extract biomolecules to the sample surface and concurrently render the sample amenable to MALDI. However, matrix application may mobilize sample metabolites and will dictate the efficiency of matrix crystallization, together limiting the lateral resolution which may be optimally achieved by MSI.

Untargeted metabolomics of human plasma reveal lipid markers unique to chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation and progressive airflow limitation, whereas idiopathic pulmonary fibrosis (IPF) is characterised by a restrictive pattern due to fibrosis and impaired gas exchange. We undertook metabolomic analysis of blood samples in IPF, COPD and healthy controls (HC) to determine differences in circulating molecules and identify novel pathogenic pathways. An untargeted metabolomics using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) was performed to profile plasma of patients with COPD (n = 21), and IPF (n = 24) in comparison to plasma from healthy controls (HC; n = 20).

Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT).

Purpose: In adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home.

Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: the multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT).

Introduction: The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain.

Methods And Analysis: The Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained 299v probiotic therapy in addition to usual care or placebo in addition to usual care.

Untargeted Liquid Chromatography-Mass Spectrometry-Based Metabolomics Analysis of Wheat Grain.

Understanding the interactions between genes, the environment and management in agricultural practice could allow more accurate prediction and management of product yield and quality. Metabolomics data provides a read-out of these interactions at a given moment in time and is informative of an organism's biochemical status. Further, individual metabolites or panels of metabolites can be used as precise biomarkers for yield and quality prediction and management.

Identification of The Canidae Iron Regulatory Hormone Hepcidin.

Hepcidins are an evolutionarily conserved class of liver-expressed peptide, from which the twenty-five amino acid hormone, hepcidin-25 (herein hepcidin), has gained significant notoriety as the master regulator of iron homeostasis in mammals. Hepcidin maintains iron homeostasis by controlling the dietary absorption of iron and the mechanisms of recycling cellular iron stores. With the physiological significance of this hormone well established, it has emerged as an informative biomarker.

Susceptibility of frogs to chytridiomycosis correlates with increased levels of immunomodulatory serotonin in the skin.

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is a skin disease responsible for the global decline of amphibians. Frog species and populations can vary in susceptibility, but this phenomenon remains poorly understood. Here, we investigated serotonin in the skin of infected and uninfected frogs.

Untargeted gas chromatography-mass spectrometry-based metabolomics analysis of kidney and liver tissue from the Lewis Polycystic Kidney rat.

Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments.

Metabolomics in chronic lung diseases.

Chronic lung diseases represent a significant global burden. Their increasing incidence and complexity render a comprehensive, multidisciplinary and personalized approach to each patient, critically important. Most recently, unique biochemical pathways and disease markers have been identified through large-scale metabolomic studies.

Characterizing the plasma metabolome during 14 days of live-high, train-low simulated altitude: A metabolomic approach.

New Findings: What is the central question of this study? Does 14 days of live-high, train-low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude.

Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study.

Background: Both anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU). The aim of this study was to determine whether serum hepcidin concentration, measured early after ICU admission in patients with anaemia, could identify a group in whom intravenous (IV) iron therapy decreased the subsequent RBC transfusion requirement.

Methods: We conducted a prospective observational study nested within a multicenter randomized controlled trial (RCT) of IV iron versus placebo.

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease.

Rodent and cell-culture models support a role for iron-related adipokine dysregulation and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, substantial human data are lacking. We examined the relationship between measures of iron status, adipokines, and insulin resistance in patients with NAFLD in the presence and absence of venesection. This study forms part of the Impact of Iron on Insulin Resistance and Liver Histology in Nonalcoholic Steatohepatitis (IIRON2) study, a prospective randomized controlled trial of venesection for adults with NAFLD.

Chytridiomycosis causes catastrophic organism-wide metabolic dysregulation including profound failure of cellular energy pathways.

Chytridiomycosis is among several recently emerged fungal diseases of wildlife that have caused decline or extinction of naïve populations. Despite recent advances in understanding pathogenesis, host response to infection remains poorly understood. Here we modelled a total of 162 metabolites across skin and liver tissues of 61 frogs from four populations (three long-exposed and one naïve to the fungus) of the Australian alpine tree frog (Litoria verreauxii alpina) throughout a longitudinal exposure experiment involving both infected and negative control individuals.

Survival, gene and metabolite responses of Litoria verreauxii alpina frogs to fungal disease chytridiomycosis.

The fungal skin disease chytridiomycosis has caused the devastating decline and extinction of hundreds of amphibian species globally, yet the potential for evolving resistance, and the underlying pathophysiological mechanisms remain poorly understood. We exposed 406 naïve, captive-raised alpine tree frogs (Litoria verreauxii alpina) from multiple populations (one evolutionarily naïve to chytridiomycosis) to the aetiological agent Batrachochytrium dendrobatidis in two concurrent and controlled infection experiments. We investigated (A) survival outcomes and clinical pathogen burdens between populations and clutches, and (B) individual host tissue responses to chytridiomycosis.

Dysregulated Erythropoietin, Hepcidin, and Bone Marrow Iron Metabolism Contribute to Interferon-Induced Anemia in Hepatitis C.

Anemia is a complication of interferon-containing hepatitis C treatments. We characterized effects of interferon-based therapy on hepcidin and erythropoietin (EPO) production, iron metabolism, hemolysis, and hematopoiesis. Standard hemopoiesis [reticulocyte hemoglobin (Hb), reticulocyte production index (RPI), free Hb, and haptoglobin], iron biochemistry, hepcidin, and EPO levels were measured in 10 subjects over 12 weeks.

Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial : A randomized trial of IV iron in critical illness.

Purpose: Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain.

Methods: The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge.

Association between serum hepcidin-25 and primary resistance to erythropoiesis-stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial.

Background: Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline multicentre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in patients with ESA-hyporesponsive CKD.

Methods: This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm.

A rapid method for profiling of volatile and semi-volatile phytohormones using methyl chloroformate derivatisation and GC-MS.

Phytohormones are central components of complex signalling networks in plants. The interplay between these metabolites, which include abscisic acid (ABA), auxin (IAA), ethylene, jasmonic acid (JA) and salicylic acid (SA), regulate plant growth and development and modulate responses to biotic and abiotic stress. Few methods of phytohormone profiling can adequately quantify a large range of plant hormones simultaneously and without the requirement for laborious or highly specialised extraction protocols.

Metabolomic profiling and genomic analysis of wheat aneuploid lines to identify genes controlling biochemical pathways in mature grain.

Metabolomics is becoming an increasingly important tool in plant genomics to decipher the function of genes controlling biochemical pathways responsible for trait variation. Although theoretical models can integrate genes and metabolites for trait variation, biological networks require validation using appropriate experimental genetic systems. In this study, we applied an untargeted metabolite analysis to mature grain of wheat homoeologous group 3 ditelosomic lines, selected compounds that showed significant variation between wheat lines Chinese Spring and at least one ditelosomic line, tracked the genes encoding enzymes of their biochemical pathway using the wheat genome survey sequence and determined the genetic components underlying metabolite variation.