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Search Results: 1 - 10 of 299295 matches for " Atkins Gerald J "
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Critical role of p38 MAPK for regeneration of the sciatic nerve following crush injury in vivo
Kato Naoki,Matsumoto Masahito,Kogawa Masakazu,Atkins Gerald J
Journal of Neuroinflammation , 2013, DOI: 10.1186/1742-2094-10-1
Abstract: Background The physiological function of p38α, which is an isoform of p38 MAPK, has been investigated previously in several studies using pharmacological inhibitors. However, the results regarding whether p38α promotes or inhibits nerve regeneration in vivo have been controversial. Methods We generated novel p38α mutant mice (sem mice) with a point mutation in the region encoding the p38α substrate-docking-site, which serves as a limited loss-of-function model of p38α. In the present study, we utilized sem mice and wild-type littermates (wt mice) to investigate the physiological role of p38α in nerve regeneration following crush injuries. Results At four weeks after crush injury, the average axon diameter and the average axon area in sem mice were significantly smaller than those in wt mice. The average myelin sheath thickness in sem mice was reduced compared to wt mice, but no significant difference was observed in the G-ratio between the two groups. The sciatic functional index value demonstrated that functional nerve recovery in sem mice following crush injury was delayed, which is consistent with the histological findings. To investigate the underlying mechanisms of these findings, we examined inflammatory responses of the sciatic nerve by immunohistochemistry and western blotting. At an early phase following crush injury, sem mice showed remarkably lower expression of inflammatory cytokines, such as TNF-α and IL-1β, than wt mice. The expression of Caspase-3 and Tenascin-C were also lower in sem mice. Conversely, at a late phase of the response, sem mice showed considerably higher expression of TNF-α and of IL-1β with lower expression of S-100 than wt mice. Conclusions This is the first study of the physiological role of p38 MAPK in nerve regeneration that does not rely on the use of pharmacological inhibitors. Our results indicate that p38α insufficiency may cause an inflammatory disorder, resulting in a delay of histological and functional nerve recovery following crush injury. We conclude that p38 MAPK has an important physiological role in nerve regeneration and may be important for controlling both initiation of inflammation and recovery from nerve injury.
Role of polyethylene particles in peri-prosthetic osteolysis: A review
Gerald J Atkins,David R Haynes,Donald W Howie,David M Findlay
World Journal of Orthopedics , 2011, DOI: 10.5312/wjo.v2.i10.93
Abstract: There is convincing evidence that particles produced by the wear of joint prostheses are causal in the peri-prosthetic loss of bone, or osteolysis, which, if it progresses, leads to the phenomenon of aseptic loosening. It is important to fully understand the biology of this bone loss because it threatens prosthesis survival, and loosened implants can result in peri-prosthetic fracture, which is disastrous for the patient and presents a difficult surgical scenario. The focus of this review is the bioactivity of polyethylene (PE) particles, since there is evidence that these are major players in the development and progression of osteolysis around prostheses which use PE as the bearing surface. The review describes the biological consequences of interaction of PE particles with macrophages, osteoclasts and cells of the osteoblast lineage, including osteocytes. It explores the possible cellular mechanisms of action of PE and seeks to use the findings to date to propose potential non-surgical treatments for osteolysis. In particular, a non-surgical approach is likely to be applicable to implants containing newer, highly cross-linked PEs (HXLPEs), for which osteolysis seems to occur with much reduced PE wear compared with conventional PEs. The caveat here is that we know little as yet about the bioactivity of HXLPE particles and addressing this constitutes our next challenge.
Sclerostin Stimulates Osteocyte Support of Osteoclast Activity by a RANKL-Dependent Pathway
Asiri R. Wijenayaka, Masakazu Kogawa, Hui Peng Lim, Lynda F. Bonewald, David M. Findlay, Gerald J. Atkins
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025900
Abstract: Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation. While evidence suggests that sclerostin has an anti-anabolic role, the possibility also exists that sclerostin has catabolic activity. To test this we treated human primary pre-osteocyte cultures, cells we have found are exquisitely sensitive to sclerostin, or mouse osteocyte-like MLO-Y4 cells, with recombinant human sclerostin (rhSCL) and measured effects on pro-catabolic gene expression. Sclerostin dose-dependently up-regulated the expression of receptor activator of nuclear factor kappa B (RANKL) mRNA and down-regulated that of osteoprotegerin (OPG) mRNA, causing an increase in the RANKL:OPG mRNA ratio. To examine the effects of rhSCL on resulting osteoclastic activity, MLO-Y4 cells plated onto a bone-like substrate were primed with rhSCL for 3 days and then either mouse splenocytes or human peripheral blood mononuclear cells (PBMC) were added. This resulted in cultures with elevated osteoclastic resorption (approximately 7-fold) compared to untreated co-cultures. The increased resorption was abolished by co-addition of recombinant OPG. In co-cultures of MLO-Y4 cells with PBMC, SCL also increased the number and size of the TRAP-positive multinucleated cells formed. Importantly, rhSCL had no effect on TRAP-positive cell formation from monocultures of either splenocytes or PBMC. Further, rhSCL did not induce apoptosis of MLO-Y4 cells, as determined by caspase activity assays, demonstrating that the osteoclastic response was not driven by dying osteocytes. Together, these results suggest that sclerostin may have a catabolic action through promotion of osteoclast formation and activity by osteocytes, in a RANKL-dependent manner.
Mother’s milk and infant death in Britain, circa 1900-1940
P.J. Atkins
Anthropology of Food , 2003,
Abstract: My contribution to this journal issue is to reconstruct the darker side of the most popular of infant foods. I will give a brief overview of contamination and disease in Britain's milk supply between 1880 and 1940, with particular reference to the impact upon infants. Not surprisingly, young children consumed a substantial proportion of market milk and, as a result, they seem to have suffered heavily from diseases such as bovine tuberculosis and summer diarrhoea. I will ask why these children were not wholly breast-fed and why relying upon artificial foods was such a risk. Also, I will give a preliminary report on my findings from data I have collected on the feeding of over three million infants, as recorded in the Medical Officer of Health Reports of 130 Local Authorities, mainly from England and Wales.
The Pathogenesis of Alphaviruses
Gregory J. Atkins
ISRN Virology , 2013, DOI: 10.5402/2013/861912
Abstract: Alphaviruses are enveloped single-stranded positive sense RNA viruses of the family Togaviridae. The genus alphavirus contains nine viruses, which are of medical, theoretical, or economic importance, and which will be considered. Sindbis virus (SINV) and Semliki Forest (SFV), although of some medical importance, have largely been studied as models of viral pathogenicity. In mice, SINV and SFV infect neurons in the central nervous system and virulent strains induce lethal encephalitis, whereas avirulent strains of SFV induce demyelination. SFV infects the developing foetus and can be teratogenic. Venezuelan Equine Encephalitis virus, Eastern Equine Encephalitis virus, and Western Equine Encephalitis virus can induce encephalitis in horses and humans. They are prevalent in the Americas and are mosquito transmitted. Ross River virus, Chikungunya virus (CHIKV), and O’nyong-nyong virus (ONNV) are prevalent in Australasia, Africa and Asia, and Africa, respectively. ONNV virus is transmitted by Anopheles mosquitoes, while the other alphaviruses are transmitted by culicine mosquitoes. CHIKV has undergone adaptation to a new mosquito host which has increased its host range beyond Africa. Salmonid alphavirus is of economic importance in the farmed salmon and trout industry. It is postulated that future advances in research on alphavirus pathogenicity will come in the field of innate immunity. 1. Introduction Alphaviruses are small, enveloped, single-stranded positive RNA viruses of the family Togaviridae (Figure 1(a)). Most of them are mosquito transmitted and also infect a variety of mammals and birds. Their intracellular multiplication involves adsorption and receptor-mediated endocytosis into the cell cytoplasm. During intracellular multiplication a gene amplification mechanism results in the formation of a subgenomic RNA species that codes for the structural proteins only and is labelled 26S RNA (Figure 1(b)). The nonstructural and structural proteins are formed from different open reading frames by posttranslational cleavage pathways, and the assembled nucleocapsids bud from areas of the cell membrane or intracellular vesicles that have acquired envelope proteins, thus forming enveloped virions [1]. Figure 1: (a) The structure of alphavirus virions (e.g., SFV). (b) Alphavirus genome structure. P62 (also known as PE2) is the precursor to the E2 and E3 proteins. The genus Alphavirus contains approximately 30 members, which probably diverged a few thousand years ago. Eight alphaviruses, all of which can infect humans as well as other animals, will be discussed
A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway
Mitali Bhattacharjee,Rajesh Raju,Aneesha Radhakrishnan,Vishalakshi Nanjappa,Babylakshmi Muthusamy,Kamlendra Singh,Dheebika Kuppusamy,Bhavya Teja Lingala,Archana Pan,Premendu Prakash Mathur,H. C. Harsha,T. S. Keshava Prasad,Gerald J. Atkins,Akhilesh Pandey,Aditi Chatterjee
Journal of Signal Transduction , 2012, DOI: 10.1155/2012/376470
Abstract: TNF-related weak inducer of apoptosis (TWEAK) is a new member of the TNF superfamily. It signals through TNFRSF12A, commonly known as Fn14. The TWEAK-Fn14 interaction regulates cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis, tissue remodeling and inflammation. Although TWEAK has been reported to be associated with autoimmune diseases, cancers, stroke, and kidney-related disorders, the downstream molecular events of TWEAK-Fn14 signaling are yet not available in any signaling pathway repository. In this paper, we manually compiled from the literature, in particular those reported in human systems, the downstream reactions stimulated by TWEAK-Fn14 interactions. Our manual amassment of the TWEAK-Fn14 pathway has resulted in cataloging of 46 proteins involved in various biochemical reactions and TWEAK-Fn14 induced expression of 28 genes. We have enabled the availability of data in various standard exchange formats from NetPath, a repository for signaling pathways. We believe that this composite molecular interaction pathway will enable identification of new signaling components in TWEAK signaling pathway. This in turn may lead to the identification of potential therapeutic targets in TWEAK-associated disorders.
TWEAK and Fn14 expression in the pathogenesis of joint inflammation and bone erosion in rheumatoid arthritis
Anak ASSK Dharmapatni, Malcolm D Smith, Tania N Crotti, Christopher A Holding, Cristina Vincent, Helen M Weedon, Andrew CW Zannettino, Timothy S Zheng, David M Findlay, Gerald J Atkins, David R Haynes
Arthritis Research & Therapy , 2011, DOI: 10.1186/ar3294
Abstract: TWEAK and Fn14 expression were detected in synovial tissues by immunohistochemistry (IHC). Selected tissues were dual labelled with antibodies specific for TWEAK and lineage-selective cell surface markers CD68, Tryptase G, CD22 and CD38. TWEAK mRNA expression was examined in human peripheral blood mononuclear cells (PBMC) sorted on the basis of their expression of CD22. sTWEAK was detected in synovial fluid from OA and RA patients by ELISA. The effect of sTWEAK on PBMC and RAW 264.7 osteoclastogenesis was examined. The effect of sTWEAK on cell surface receptor activator of NF Kappa B Ligand (RANKL) expression by human osteoblasts was determined by flow cytometry.TWEAK and Fn14 expression were significantly higher in synovial tissue from all patient groups compared to the synovial tissue from control subjects (P < 0.05). TWEAK was significantly higher in active compared with inactive RA tissues (P < 0.05). TWEAK expression co-localised with a subset of CD38+ plasma cells and with CD22+ B-lymphocytes in RA tissues. Abundant TWEAK mRNA expression was detected in normal human CD22+ B cells. Higher levels of sTWEAK were observed in synovial fluids isolated from active RA compared with OA patients. sTWEAK did not stimulate osteoclast formation directly from PBMC, however, sTWEAK induced the surface expression of RANKL by human immature, STRO-1+ osteoblasts.The expression of TWEAK by CD22+ B cells and CD38+ plasma cells in RA synovium represents a novel potential pathogenic pathway. High levels of sTWEAK in active RA synovial fluid and of TWEAK and Fn14 in active RA tissue, together with the effect of TWEAK to induce osteoblastic RANKL expression, is consistent with TWEAK/Fn14 signalling being important in the pathogenesis of inflammation and bone erosion in RA.TWEAK (TNF-like weak inducer of apoptosis) is a recently described member of the TNF superfamily. It is reported to exert a variety of biological effects through ligation with its receptor, Fn14. The biological effe
Prosthetic education: Are occupational therapy students’ needs being met?  [PDF]
Marilyn Mitchell, Mark Gorelick, David I. Anderson, Diane J. Atkins
Open Journal of Therapy and Rehabilitation (OJTR) , 2014, DOI: 10.4236/ojtr.2014.21002
Abstract: Based on a previous survey on prosthetics and orthotics training in occupational therapy (OT) [1], we developed a 14-question online questionnaire that was made available to the directors of 167 occupational therapy programs (Masters and Ph.D.) in the US and Canada. Fifty- two surveys were completed for a response rate of 31%. Overall, the results indicated that since the previous survey, little has changed in the amount of time and emphasis OT faculty assign to providing training in prosthetics and orthotics, or in the training experiences, OT students receive. Notably, only a few hours of the total OT curriculum is devoted to training in prosthetics. For the majority of programs (62%) the content was embedded within related classes. Only 32% of programs had a required lecture in prosthetics/orthotics. Despite the lack of time given in the curriculum, 85% of program directors thought that training in prosthetics/orthotics was important or very important. The use of prosthetic simulators was reported as the single most desirable training tool. However, lack of time and overcrowding in the curriculum were cited as the greatest barriers to providing more training to students. We elaborate on these findings, discuss their implications for OT students and practitioners, and provide specific recommendations about how to overcome the barriers and enhance upper limb amputee exposure and knowledge through the prosthetic training experience.
Yochelcionella (Mollusca, Helcionelloida) from the lower Cambrian of North America
Atkins C J,Peel J S
Bulletin of Geosciences , 2008, DOI: 10.3140/bull.geosci.2008.01.023
Abstract: Five named species of the helcionelloid mollusc genus Yochelcionella Runnegar & Pojeta, 1974 are recognized from the lower Cambrian (Cambrian Series 2) of North America: Yochelcionella erecta (Walcott, 1891), Y. americana Runnegar &Pojeta, 1980, Y. chinensis Pei, 1985, Y. greenlandica Atkins & Peel, 2004 and Y. gracilis Atkins & Peel, 2004, linking lower Cambrian outcrops along the present north-eastern seaboard. Yochelcionella erecta, an Avalonian species, is described for the first time; other species are derived from Laurentia. A revised concept of the Chinese species, Y. chinensis, is based mainly on a large sample from the Forteau Formation of western Newfoundland and the species may have stratigraphic utility between Cambrian palaeocontinents.
Implicit particle methods and their connection with variational data assimilation
Ethan Atkins,Matthias Morzfeld,Alexandre J. Chorin
Physics , 2012,
Abstract: The implicit particle filter is a sequential Monte Carlo method for data assimilation that guides the particles to the high-probability regions via a sequence of steps that includes minimizations. We present a new and more general derivation of this approach and extend the method to particle smoothing as well as to data assimilation for perfect models. We show that the minimizations required by implicit particle methods are similar to the ones one encounters in variational data assimilation and explore the connection of implicit particle methods with variational data assimilation. In particular, we argue that existing variational codes can be converted into implicit particle methods at a low cost, often yielding better estimates, that are also equipped with quantitative measures of the uncertainty. A detailed example is presented.
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