42,740 research outputs found
Huntington's disease: An immune perspective
Get PDFCopyright © 2011 Annapurna Nayaketal. This article has been made available through the Brunel Open Access Publishing Fund.Huntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.U. Kishore acknowledges funding via BRIEF and Brunel University’s strategic funding for the Centre of Infection, Immunity and Disease Mechanisms
Cloning expression and characterisation of the globular head regions of mouse CIQ
Get PDFThis thesis was submitted for the degree of Master of Philosophy and awarded by Brunel UniversityThe classical pathway of complement system, activated by immune complexes, involves binding of globular heads of C1q to the Fc regions of aggregated IgG or IgM. At the C-terminal region of C1q, is globular head region (gC1q) where each globular head is composed of one A (ghA), one B (ghB) and one C (ghC) chain. In order to understand modularity of gC1q region of mouse C1q and to generate useful reagents for in vivo studies, we have expressed these recombinant individual heads of mouse C1q in Escherichia coli as soluble proteins linked to maltose-binding protein (MBP). This included RNA extraction and cDNA synthesis from mouse spleen, using appropriate primers, full-length mouse C1q A, B and C chains were amplified first. Following this, using the appropriate full length C1q chains, globular heads of mouse C1q A, B and C chains were amplified (mghA, mghB and mghC respectively). We have examined their interaction with heat-aggregated mouse IgG. These fusion proteins (MBP-ghA, -ghB, and -ghC) were found to bind differentially to mouse IgG. ghA and ghB were found to bind highest with IgG. IgG subtypes were purified and their interaction with native human C1q was also studied. Dose-dependent binding was observed. Interaction of recombinant globular heads of C1q with mouse IgM was also examined. ghC was found to bind highest with IgM although ghB and ghA also showed binding to IgM. The ability of these recombinant heads to inhibit complement-mediated lysis was also examined. Both MBP-ghA and MBP-ghB also inhibited C1q-dependent hemolysis of IgG sensitized sheep erythrocytes. Interaction and binding of these globular heads with recombinant prion peptide was also studied. The individual globular heads of mouse C1q were also found to bind to recombinant mouse PrP peptide which will aid in better understanding of pathogenesis of prion disease. Further studies involved interaction of recombinant mouse globular heads of C1q (mghA, mghB and mghC) with pentraxin PTX-3. mghB and mghC showed highest binding (mghB>mghC) to PTX3 as compared to mghA. The study of recombinant gC1q region heads will help in understanding the effects of PTX3 activation on the complement system. Collaborative studies examined the most variable residues in mouse gC1q region as well as alignment of mouse gC1q region with human gC1q region. The expression and functional characterisation of individual mouse gC1q domains has allowed to examine specificity and selectivity of individual globular heads of mouse C1q to known ligands. Production of mouse gC1q domains will be helpful in antibody mapping of anti-C1q autoantibodies recognising gC1q region
The dialogue between the author and the hero in the “Notes” of G. R. Derzhavin
No full textВ центре внимания автора статьи «Записки» Г. Р. Державина, представляющие по своей сути его автобиографию. Труд этот был создан на закате жизни, он включает все важнейшие события жизни Г. Р. Державина, поэта и государственного деятеля. Рассказ ведется от третьего лица, что придает особую атмосферу повествованию, выстраивается своеобразный диалог между автором и героем, все это и является предметом исследования автора статьи.The focus of the author of the article “Notes” G. R. Derzhavin, representing in essence his autobiography. This work was created at the end of his life; it includes all the most important events in the life of G. R. Derzhavin, poet and statesman. The story is told in a third person, which gives a special atmosphere to the story, a certain dialogue emerges between the author and the hero, all this is the subject of the author's research
Aging is associated with cardiac autonomic nerve fiber depletion and reduced cardiac and circulating BDNF levels
No full textBackground Aging is a multifactorial process associated with an impairment of autonomic nervous system (ANS) function. Progressive ANS remodeling includes upregulation of expression of circulating catecholamines and depletion of cardiac autonomic nerve fibers, and it is responsible, in part, for the increased susceptibility to cardiac diseases observed in elderly subjects. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are involved in synaptogenesis and neurite outgrowth processes, supporting neuronal cell differentiation and maturation. However, whether and how these factors and their downstream signaling are involved in cardiac aging remains unclear. Here, we tested whether, in the aged heart, the overall extent of autonomic fibers is reduced, owing to lower production of trophic factors such as BDNF and NGF. Methods In vivo, we used young (age: 3 months; n = 10) and old (age: 24 months; n = 11) male Fisher rats, whereas, we used human neuroblastoma (SH-SY5Y) cells in vitro. Results Compared to the young rats, old rats displayed a marked reduction in the overall ANS fiber density, affecting both sympathetic and cholinergic compartments, as indicated by dopamine β-hydroxylase (dβh) and vesicular acetylcholine transporter (VaChT) immunohistochemical staining. In addition, a marked downregulation of GAP-43 and BDNF protein was observed in the left ventricular lysates of old rats compared to those of young rats. Interestingly, we did not find any significant difference in cardiac NGF levels between the young and old groups. To further explore the impact of aging on ANS fibers, we treated SH-SY5Y cells in vitro with serum obtained from young and old rats. Sera from both groups induced a remarkable increase in neuronal sprouting, as evidenced by a crystal violet assay. However, this effect was blunted in cells cultured with old rat serum and was accompanied by a marked reduction in GAP-43 and BDNF protein levels. Conclusions Our data indicate that physiological aging is associated with an impairment of ANS structure and function and that reduced BDNF levels are responsible, at least in part, for these phenomena
Uterine immunity and microbiota: A shifting paradigm
Get PDFThe female reproductive tract harbors distinct microbial communities, as in the vagina, cervical canal, uterus, and fallopian tubes. The nature of the vaginal microbiota is well-known; in contrast, the upper reproductive tract remains largely unexplored. Alteration in the uterine microbiota, which is dependent on the nutrients and hormones available to the uterus, is likely to play an important role in uterine-related diseases such as hysteromyoma, adenomyosis, and endometriosis. Uterine mucosa is an important tissue barrier whose main function is to offer protection against pathogens and other toxic factors, while maintaining a symbiotic relationship with commensal microbes. These characteristics are shared by all the mucosal tissues; however, the uterine mucosa is unique since it changes cyclically during the menstrual cycle as well as pregnancy. The immune system, besides its role in the defense process, plays crucial roles in reproduction as it ensures local immune tolerance to fetal/paternal antigens, trophoblast invasion, and vascular remodeling. The human endometrium contains a conspicuous number of immune cells, mainly Natural Killers (NK) cells, which are phenotypically distinct from peripheral cytotoxic NK, cells and macrophages. The endometrium also contains few lymphoid aggregates comprising B cell and CD8+ T cells. The number and the phenotype of these cells change during the menstrual cycle. It has become evident in recent years that the immune cell phenotype and function can be influenced by microbiota. Immune cells can sense the presence of microbes through their pattern recognition receptors, setting up host-microbe interaction. The microbiota exerts an appropriately controlled defense mechanism by competing for nutrients and mucosal space with pathogens. It has recently been considered that uterus is a non-sterile compartment since it seems to possess its own microbiota. There has been an increasing interest in characterizing the nature of microbial colonization within the uterus and its apparent impact on fertility and pregnancy. This review will examine the potential relationship between the uterine microbiota and the immune cells present in the local environment
A non-redundant role of complement protein C1q in normal and adverse pregnancy
Get PDFAvailability of data and materials: Not applicable.Copyright © The Author(s) 2022. Complement component 1q (C1q) is the recognition molecule of the classical pathway of the complement system that can bind to an array of closely spaced antigen-bound immunoglobulin G (IgG) and IgM antibodies. In addition to its involvement in defence against a range of pathogens and clearance of apoptotic and necrotic cells, C1q has also been implicated in immune and non-immune homeostasis. C1q is locally produced by immune cells such as monocytes, macrophages, and dendritic cells. C1q is also synthesized by decidual endothelial cells, thus acting as a link between decidual cells and trophoblasts, as well as contributing to the remodelling of spiral arteries. Furthermore, C1q is produced by the extravillous trophoblasts (EVTs) invading the decidua. As a pro-angiogenic molecule, C1q is also important for normal placentation processes as it favors the active angiogenesis in the developing decidua. These observations have been validated by C1q gene knock-out mice which showed pre-eclampsia (PE)-like symptoms, characterized by hypertension, proteinuria, glomerular endotheliosis, and increased soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio, and increased oxidative stress. The role of C1q in normal and adverse human pregnancy is being studied extensively due to its absence or low level as a likely precipitating factor for the development of PE.Funding: Not applicable
Gravastars in f(R, G) gravity
Get PDFThis paper is focused on the study of gravitational vacuum stars or, briefly, gravastars in f(R, G) gravity, where R and G stand for the Ricci scalar and Gauss–Bonnet invariant term, respectively. Due to the involvement of highly non-linear differential equations, solutions are found by using some appropriate numerical techniques. The main structure of gravastars has been discussed according to core, shell, and exterior regions for a well-known f(R, G) gravity cosmological model. Mass–radius evolution is described graphically for the considered gravastar, and it is shown that the mass is directly proportional to the radius.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Environmental and economic impacts of photovoltaic integration in concentrated solar power plants
No full textThis study conducted an environmental and economic assessment of an innovative hybrid energy generation system, a CSP+ plant, which integrates photovoltaic (PV) panels in a concentrated solar power (CSP) setup. The CSP+ concept uses a beam splitter that transmits part of the incident solar spectrum towards the PV cells for electricity generation and reflects ultraviolet and infrared light to the receiver tube for heating. This system allows more efficient use of solar radiation in a compact system with optimal efficiency. The environmental impacts were assessed using the life cycle assessment (LCA) methodology, focusing on the climate change impact category. The economic impacts were calculated using the levelized cost of electricity (LCOE) and the levelized cost of heat (LCOH). Both assessments considered a cradle-to-grave perspective in three scenarios (SC). SCI considered only electricity generation, while SCII involved the combined production of electricity and heat. These scenarios were compared to conventional CSP and PV technologies (SCIII) and benchmark values from the literature. The LCA results showed SCII was the most preferable: the impacts on climate change were reduced by up to 83% for electricity production and up to 97% for heat production compared to benchmark values. In SCII, the LCOE and the LCOH in the CSP+ plant were lower than the average benchmark values, with reductions of up to 70% for electricity and 40% for heat. The sensitivity analysis showed that the environmental performance was strongly influenced by the operating lifetime. For economic performance, the weighted cost of capital was the most influential factor.This work was part of the CSP+ ICON project, funded by VLAIO (Flanders Innovation and Entrepreneurship) under project number HBC.2020.2451, and was supported by the Flemish spearhead clusters Flux50 and Catalisti. The authors also thank Amelie Müller, Annabel Vella, and Roel Degens for their support during the execution of the work
Introduction: Starring the Author
No full textLiterary celebrity is by now a familiar feat of contemporary literary culture, but it continues to raise complex questions about the history and development of fame, the interplay between the cultural marketplace and the official culture of critics and the canon, and the relation between authorial agency and public appropriation. This introduction addresses these questions by approaching literary celebrity as a merging of two discursive constructions: the celebrity-function and the author-function. By combining insights from celebrity studies, literary history and cultural memory studies, the introduction conceptualizes literary celebrity as a discursive construction with several variables, such as the author’s self-presentation, the circulation of his public identity, changing opinions on literature and writership, and the public afterlife of the author’s image
Spherically symmetric solution of f(R,G) gravity at low energy
No full textThe weak-field and slow-motion limit of f(R,G) gravity is developed up to (v/c)(4) order in a spherically symmetric background. Considering the Taylor expansion of a general function f around vanishing values of R and G, we present general vacuum solutions up to (v/c)(4) order for the gravitational field generated by a ball-like source. The spatial behaviors at (v/c)(2) order are the same for f(R,G) gravity and f(R) gravity, and their corresponding real valued static behaviors are presented and compared with the one in general relativity. The static Yukawa-like behavior is proved to be compatible with the previous result of the most general fourth-order theory. At (v/c)(4) order, the static corrections to the Yukawa-like behavior for f(R,G) gravity, f(R) gravity, and the Starobinsky gravity are presented and compared with the one in general relativity.National Natural Science Foundation of China [11120101004, 11475006]SCI(E)[email protected]; [email protected]
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