Clostridium perfringens type D epsilon prototoxin. Some chemical, immunological and biological properties of a highly purified prototoxin

Highly purified Cl. perfringens type D epsilon prototoxin was prepared by ammonium sulphate precipitation and DEAE cellulose chromatography of culture filtrate of cultures of Cl. perfringens type D (Strain ET 468). Preparations of prototoxin were electrophoretically heterogeneous. The protein bands demonstrable in polyacrylamide gel electrophoresis were, however, all immunologically identical and toxic. The faster moving bands were shown to be degradation products of the main prototoxin band which was the slowest moving of the major bands. There was an inverse relationship between electrophoretic mobility and the activation ratio of these degradation products. The unde- graded prototoxin could be separated from its degradation products by CM cellulose chromatography but degradation appears to be a continual process and isolation of an absolutely pure product was not achieved.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Enzymatic activation of Clostridium perfringens epsilon prototoxin and some biological properties of activated toxin

Maximal activation of Clostridium perfringens epsilon toxin was only achieved by the combined action of trypsin and chymotrypsin. Impure preparations of trypsin, presumably containing small amounts of chymotrypsin were more efficient in activating prototoxin than pure trypsin. Activated toxin was readily absorbed by brain tissue and smaller amounts were possibly absorbed by kidney tissue. Other tissues absorbed only very small amounts of toxin. Injection of mice with toxoid 3 h prior to challenge with toxin increased their resistance 32 times.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Design and analysis of the tracker bridge for the Hobby-Eberly Telescope wide field upgrade

A large structural weldment has been designed to serve as the new star tracker bridge for the Wide Field Upgrade to the Hobby-Eberly Telescope at McDonald Observatory in support of the Hobby-Eberly Telescope Dark Energy Experiment‡. The modeling approach, analysis techniques and design details will be of interest to designers of large structures where stiffness is the primary design driver. The design includes detailed structural analysis using finite element models to maximize natural frequency response and limit deflections and light obscuration. Considerable fabrication challenges are overcome to allow integration of precision hardware required for positioning the corrector optics to a precision of less than 5 microns along the 4-meter travel range. Detailed descriptions of the bridge geometry, analysis results and challenging fabrication issues are discussed.Center for Electromechanic

Spexin-expressing neurons in the magnocellular nuclei of the human hypothalamus

Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel neuropeptide spexin (SPX) within the human magnocellular hypothalamus. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. For the first time we describe SPX expressing neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the human hypothalamus using immunohistochemical and fluorescent methods, key regions involved in the mechanisms of osmotic homeostasis, energy expenditure, consummatory behaviour, reproductive processes, social recognition and stress responses. The vast majority of neurons located in both examined neurosecretory nuclei show abundant SPX expression and this may indirectly implicate a potential contribution of SPX signalling to the hypothalamic physiology in the human brain. © 2020 Elsevier B.V

Atoms interacting with intense, high-frequency laser pulses: Effect of the magnetic-field component on atomic stabilization

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GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

The role of brain gaseous neurotransmitters in anxiety

Although anxiety is perhaps one of the most significant current medical and social problems, the neurochemical mechanistic background of this common condition remains to be fully understood. Multifunctional regulatory gasotransmitters are novel, atypical inorganic factors of the brain that are involved in the mechanisms of anxiety responses. Nitric oxide (NO) signaling shows ambiguous action in animal models of anxiety, while NO donors exert anxiogenic or anxiolytic effect depending on their chemical structure, dose, treatment schedule and gas release rapidity. The majority of NO synthase inhibitors act as a relatively potent axiolytic agents, while hydrogen sulfide (H2S) and carbon monoxide (CO) delivered experimentally in the form of “slow” or “fast” releasing donors have recently been considered as anxiolytic neurotransmitters. In this comprehensive review we critically summarize the literature regarding the intriguing roles of NO, H2S and CO in the neuromolecular mechanisms of anxiety in the context of their putative, yet promising therapeutic application. A possible mechanism of gasotransmitter action at the level of anxiety-related synaptic transmission is also presented. Brain gasesous neuromediators urgently require further wide ranging studies to clarify their potential value for the current neuropharmacology of anxiety disorders

Helminth Sensing at the Intestinal Epithelial Barrier—A Taste of Things to Come

Human intestinal helminth infection affects more than 1 billion people often in the world's most deprived communities. These parasites are one of the most prevalent neglected tropical diseases worldwide bringing huge morbidities to the host population. Effective treatments and vaccines for helminths are currently limited, and therefore, it is essential to understand the molecular sensors that the intestinal epithelium utilizes in detecting helminths and how the responding factors produced act as modulators of immunity. Defining the cellular and molecular mechanisms that enable helminth detection and expulsion will be critical in identifying potential therapeutic targets to alleviate disease. However, despite decades of research, we have only recently been able to identify the tuft cell as a key helminth sensor at the epithelial barrier. In this review, we will highlight the key intestinal epithelial chemosensory roles associated with the detection of intestinal helminths, summarizing the recent advances in tuft cell initiation of protective type 2 immunity. We will discuss other potential sensory roles of epithelial subsets and introduce enteroendocrine cells as potential key sensors of the microbial alterations that a helminth infection produces, which, given their direct communication to the nervous system via the recently described neuropod, have the potential to transfer the epithelial immune interface systemically. © Copyright © 2020 Faniyi, Wijanarko, Tollitt and Worthington