Early onset preeclampsia is characterized by altered placental lipid metabolism and a premature increase in circulating FABP4

Preeclampsia is a pregnancy-associated disorder that manifests as a sudden increase in maternal blood pressure accompanied by proteinuria. Because the placenta is a key organ in preeclampsia, we used proteomic and lipidomic analyses to compare placentae from preeclamptic and gestational age matched control pregnancies. Fatty acid binding protein 4 (FABP4), enoyl-CoA dehydrogenase and delta-3,5-delta-2,4-dienoyl-CoA isomerase had altered abundance in preeclamptic placentae compared to controls. FABP4 placental protein and RNA and plasma levels were all increased in early-onset preeclampsia (prior to 28 weeks gestation) compared to controls (6-fold, 3.3-fold and 3.5-fold respectively). After 28 weeks, FABP4 protein in control placenta and plasma increased to the same concentrations as in preeclampsia. Total tetracosapentaenoic acid in preeclamptic placentae was decreased to 0.6 of control levels before 28 weeks. The data indicate a disruption of fatty acid transport and metabolism in the placenta in early onset preeclampsia that is reflected in the maternal plasma

The Manchester Color Wheel: development of a novel way of identifying color choice and its validation in healthy, anxious and depressed individuals

Abstract Background For the purposes of our research programme we needed a simple, reliable and validated method for allowing choice of a color in response to a series of questions. On reviewing the literature no such instrument was available and this study aimed to rectify this situation. This was achieved by developing a simple method of presenting a series of colors to people validating it in healthy volunteers and in individuals where color choice might be distorted, namely anxiety and depression. Methods A series of different presentations of four shades of eight colors and grey, as well as black and white were evaluated. 'Mood', 'favourite' and 'drawn to' colors were assessed in 105 healthy, 108 anxious and 110 depressed participants. The positive, neutral or negative attribution of these colors was recorded in a further 204 healthy volunteers. Results The circular presentation of colors was most favoured (Color Wheel). Yellow was the most 'drawn to' color and blue the commonest 'favourite' color in all subjects. Yellow was most often associated with a normal mood and grey with an anxious or depressed mood. Different shades of the same color had completely different positive or negative connotations. Reproducibility was exceptionally high when color choice was recorded in positive, neutral or negative terms. Conclusions The Color Wheel could be used to assess health status, mood or even treatment outcome in a variety of clinical situations. It may also have utility in circumstances where verbal communication may not be optimal, such as with children.</p

Characterization of

ABSTRACT Neuropeptide Y (NPY) is a 36-amino acid peptide discovered in the early 1980s that belongs to a family of peptides that includes pancreatic polypeptides (PP) and peptide YY (PYY) The use of various cloning techniques has resulted in the identification of five receptors to date (Y 1 , Y 2 , Y 4 , Y 5 , and y 6

Real world uptake, safety profile and outcomes of docetaxel in newly diagnosed metastatic prostate cancer

Objectives: To investigate the uptake, safety and efficacy of docetaxel chemotherapy in hormone-naïve metastatic prostate cancer (mPC) in the first year of use outside of a clinical trial. Subjects/patients and Methods: Patients in the West of Scotland Cancer Network (WoSCAN) with newly diagnosed mPC were identified from the regional multidisciplinary team (MDT) meetings and their treatment details were collected from electronic patient records. The rate of febrile neutropenia, hospitalisations, time to progression and overall survival were compared between those patients who received docetaxel and androgen deprivation therapy (ADT), or ADT alone using survival analysis. Results: Out of 270 eligible patients, 103 received docetaxel (38.1%). 35 patients (34%) were hospitalised and there were 17 episodes of febrile neutropenia (16.5%). Two patients (1.9%) died within 30 days of chemotherapy. Patients who received ADT alone had an increased risk of progression (HR 2.03, 95% CI (1.27, 3.25), log-rank test, p= 0.002) and had an increased risk of death (HR 5.88, 95% CI 2.52, 13.72, log-rank p=0.001) compared to the docetaxel group. The risk of febrile neutropenia was nine times greater if chemotherapy was started within three weeks of ADT initiation (95% CI (1.22,77.72) p= 0.032). Conclusion: Docetaxel chemotherapy in hormone-naïve mPC has significant toxicities, but has a similar effect on time to progression and overall survival as seen in randomised trials. Chemotherapy should be started 3 weeks or more after androgen deprivation

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

A Small-Molecule Inhibitor of T. gondii Motility Induces the Posttranslational Modification of Myosin Light Chain-1 and Inhibits Myosin Motor Activity

Toxoplasma gondii is an obligate intracellular parasite that enters cells by a process of active penetration. Host cell penetration and parasite motility are driven by a myosin motor complex consisting of four known proteins: TgMyoA, an unconventional Class XIV myosin; TgMLC1, a myosin light chain; and two membrane-associated proteins, TgGAP45 and TgGAP50. Little is known about how the activity of the myosin motor complex is regulated. Here, we show that treatment of parasites with a recently identified small-molecule inhibitor of invasion and motility results in a rapid and irreversible change in the electrophoretic mobility of TgMLC1. While the precise nature of the TgMLC1 modification has not yet been established, it was mapped to the peptide Val46-Arg59. To determine if the TgMLC1 modification is responsible for the motility defect observed in parasites after compound treatment, the activity of myosin motor complexes from control and compound-treated parasites was compared in an in vitro motility assay. TgMyoA motor complexes containing the modified TgMLC1 showed significantly decreased motor activity compared to control complexes. This change in motor activity likely accounts for the motility defects seen in the parasites after compound treatment and provides the first evidence, in any species, that the mechanical activity of Class XIV myosins can be modulated by posttranslational modifications to their associated light chains

Identifying invasive species threats, pathways, and impacts to improve biosecurity

Managing invasive species with prevention and early-detection strategies can avert severe ecological and economic impacts. Horizon scanning, an evidence-based process combining risk screening and consensus building to identify threats, has become a valuable tool for prioritizing invasive species management and prevention. We assembled a working group of experts from academic, government, and nonprofit agencies and organizations, and conducted a multi-taxa horizon scan for Florida, USA, the first of its kind in North America. Our primary objectives were to identify high-risk species and their introduction pathways, to detail the magnitude and mechanism of potential impacts, and, more broadly, to demonstrate the utility of horizon scanning. As a means to facilitate future horizon scans, we document the process used to generate the list of taxa for screening. We evaluated 460 taxa for their potential to arrive, establish, and cause negative ecological and socioeconomic impacts, and identified 40 potential invaders, including alewife, zebra mussel, crab-eating macaque, and red swamp crayfish. Vertebrates and aquatic invertebrates posed the greatest invasion threat, over half of the high-risk taxa were omnivores, and there was high confidence in the scoring of high-risk taxa. Common arrival pathways were ballast water, biofouling of vessels, and escape from the pet/aquarium/horticulture trade. Competition, predation, and damage to agriculture/forestry/aquaculture were common impact mechanisms. We recommend full risk analysis for the high-risk taxa; increased surveillance at Florida's ports, state borders, and high-risk pathways; and periodic review and revision of the list. Few horizon scans detail the comprehensive methodology (including list-building), certainty estimates for all scoring categories and the final score, detailed pathways, and the magnitude and mechanism of impact. Providing this information can further inform prevention efforts and can be efficiently replicated in other regions. Moreover, harmonizing methodology can facilitate data sharing and enhance interpretation of results for stakeholders and the general public.</p

GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine s

ABSTRACT GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured GPR139 receptor activity from recombinant cells after treatment with amino acids, orphan ligands, serum, and tissue extracts. GPR139 activity was measured using guanosine 59-O-(3-[ Sequence alignment revealed that GPR139 is highly conserved across species, and RNA sequencing studies of rat and human tissues indicated its exclusive expression in the brain and pituitary gland. Immunohistochemical analysis showed specific expression of the receptor in circumventricular regions of the habenula and septum in mice. Together, these findings suggest that L-Trp and L-Phe are candidate physiologic ligands for GPR139, and we hypothesize that this receptor may act as a sensor to detect dynamic changes of L-Trp and L-Phe in the brain