Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders

Pathogen reduction/inactivation of products for the treatment of bleeding disorders:what are the processes and what should we say to patients?

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered

Application guide for omics approaches to cell signaling

Research in signal transduction aims to identify the functions of different signaling pathways in physiological and pathological states. Traditional techniques using biochemical, genetic or cell biological approaches have made important contributions to our understanding of cellular signaling. However, the single-gene approach does not take into account the full complexity of cell signaling. With the availability of omics techniques, great progress has been made in understanding signaling networks. Omics approaches can be classified into two categories: 'molecular profiling', including genomic, proteomic, post-translational modification and interactome profiling; and 'molecular perturbation', including genetic and functional perturbations

The Event Horizon General Relativistic Magnetohydrodynamic Code Comparison Project

Recent developments in compact object astrophysics, especially the discovery of merging neutron stars by LIGO, the imaging of the black hole in M87 by the Event Horizon Telescope, and high- precision astrometry of the Galactic Center at close to the event horizon scale by the GRAVITY experiment motivate the development of numerical source models that solve the equations of general relativistic magnetohydrodynamics (GRMHD). Here we compare GRMHD solutions for the evolution of a magnetized accretion flow where turbulence is promoted by the magnetorotational instability from a set of nine GRMHD codes: Athena++, BHAC, Cosmos++, ECHO, H-AMR, iharm3D, HARM-Noble, IllinoisGRMHD, and KORAL. Agreement among the codes improves as resolution increases, as measured by a consistently applied, specially developed set of code performance metrics. We conclude that the community of GRMHD codes is mature, capable, and consistent on these test problems

Nutrient use by tropical ant communities varies among three extensive elevational gradients: A cross-continental comparison

Aim: Many studies demonstrate that climate limits invertebrates along tropical elevational gradients, but we have only a rudimentary understanding of the role of nutrient limitation and climatic seasonality. Here we examined the relationships between ant community structure, nutrient use and season along three undisturbed elevational gradients, each from a different continent. Location: Ecuador (South America), Papua New Guinea (PNG: Oceania), Tanzania (Africa). Time period: 2011–2014. Major taxa studied: Ants. Methods: Along each of the three gradients, we placed six distinct nutrient types (amino acid, sucrose, sucrose + amino acid, lipid, NaCl, H2O). In total, we distributed 2370 baits at 38 sites from 203 m to 3972 m. We used generalized linear models to test for the effects of elevation and season on ant species richness and activity and relative nutrient use. We also tested if changes in ant trophic guilds corresponded to changes in the use of particular nutrients. Results: Both species richness and activity decreased with elevation along each gradient. However, there were significant interaction effects among elevation, region and season, as ant activity in the dry season was higher in Ecuador and Tanzania but lower in PNG. Relative nutrient use varied among regions: ant preference for some nutrients changed with increasing elevation in Ecuador (decrease in lipid use) and Tanzania (decrease in amino acid and H2O use), while season affected nutrient use in PNG. There were common trends in trophic guilds along the three elevational gradients (e.g. proportional increase of predators), but these did not explain most of the nutrient use patterns. Main conclusion: While the structure of ant communities changed similarly with elevation, both the seasonal and elevational effects on nutrient use by ants differed between continents. We argue that regional differences in climate and nutrient availability rather than ant functional composition shape nutrient use by ants