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Search Results: 1 - 10 of 401705 matches for " Gillian M. Stanfield "
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TRY-5 Is a Sperm-Activating Protease in Caenorhabditis elegans Seminal Fluid
Joseph R. Smith,Gillian M. Stanfield
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002375
Abstract: Seminal fluid proteins have been shown to play important roles in male reproductive success, but the mechanisms for this regulation remain largely unknown. In Caenorhabditis elegans, sperm differentiate from immature spermatids into mature, motile spermatozoa during a process termed sperm activation. For C. elegans males, sperm activation occurs during insemination of the hermaphrodite and is thought to be mediated by seminal fluid, but the molecular nature of this activity has not been previously identified. Here we show that TRY-5 is a seminal fluid protease that is required in C. elegans for male-mediated sperm activation. We observed that TRY-5::GFP is expressed in the male somatic gonad and is transferred along with sperm to hermaphrodites during mating. In the absence of TRY-5, male seminal fluid loses its potency to transactivate hermaphrodite sperm. However, TRY-5 is not required for either hermaphrodite or male fertility, suggesting that hermaphrodite sperm are normally activated by a distinct hermaphrodite-specific activator to which male sperm are also competent to respond. Within males, TRY-5::GFP localization within the seminal vesicle is antagonized by the protease inhibitor SWM-1. Together, these data suggest that TRY-5 functions as an extracellular activator of C. elegans sperm. The presence of TRY-5 within the seminal fluid couples the timing of sperm activation to that of transfer of sperm into the hermaphrodite uterus, where motility must be rapidly acquired. Our results provide insight into how C. elegans has adopted sex-specific regulation of sperm motility to accommodate its male-hermaphrodite mode of reproduction.
Open questions: missing pieces from the immunological jigsaw puzzle
Griffiths Gillian M
BMC Biology , 2013, DOI: 10.1186/1741-7007-11-10
Abstract:
Global Diversity and Review of Siphonophorae (Cnidaria: Hydrozoa)
Gillian M. Mapstone
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087737
Abstract: In this review the history of discovery of siphonophores, from the first formal description by Carl Linnaeus in 1785 to the present, is summarized, and species richness together with a summary of world-wide distribution of this pelagic group within the clade Hydrozoa discussed. Siphonophores exhibit three basic body plans which are briefly explained and figured, whilst other atypical body plans are also noted. Currently, 175 valid siphonophore species are recognized in the latest WoRMS world list, including 16 families and 65 genera. Much new information since the last review in 1987 is revealed from the first molecular analysis of the group, enabling identification of some new morphological characters diagnostic for physonect siphonophores. Ten types of nematocysts (stinging cells) are identified in siphonophores, more than in any other cnidarian; these are incorporated into batteries in the side branches of the tentacles in most species (here termed tentilla), and tentilla are reviewed in the last section of this paper. Their discharge mechanisms are explained and also how the tentilla of several physonect siphonophores are modified into lures. Of particular interest is the recent discovery of a previously unknown red fluorescent lure in the tentilla of the deep sea physonect Erenna, the first described example of emission of red light by an invertebrate to attract prey.
SPECIAL ARTICLE: The complete paediatrician: attributes of good practice
J. Paget Stanfield
African Health Sciences , 2003,
Abstract: The attributes which the considers help to make up good paediatric practice are discussed. Some of the problems associated with their achievement are examined. All of these ingredients can never be possessed by any one of us though each of us should have them as our aim. Their full spectrum, to be evident in practice, needs us to be members of a team. African Health Science 2003 3(1); 40-46
Land of a Couple of Dances: Global and Local Influences on Freestyle Play in Dance Dance Revolution
Gillian
Fibreculture Journal , 2006,
Abstract: This paper traces successful and unsuccessful attempts to shape the meanings of the video game Dance Dance Revolution, specifically with reference to what "dancing" means in this context, as the game moves between various interested parties - game developers, players, Internet forum participants, and other media producers. Drawing on Actor-Network Theory and the network analyses of Manuel Castells, the paper reconstructs the forces shaping players' stylistic decisions through an analysis of dance game machines and software, and of a single forum thread on DDRFreak.com, a major website in the dance game community. The paper asks who decides how DDR players dance and at what times? Are the decisions about play made in the development meeting, the arcade, competitions, online or around the home console? Globally, how do some regions or groups emerge as experts or leaders in play style? Analysis indicates that within the United States, Californian players from major cities dominate discussion, supported by the global flows of people, resources, and capital through the state. The dominant players support their stated norms for play through recourse to mainstream conceptions of masculinity, rap music and associated styles of dance.
Lifestyle in adults aged 35 years who were born with open spina bifida: prospective cohort study
Gillian M Hunt, Pippa Oakeshott
Fluids and Barriers of the CNS , 2004, DOI: 10.1186/1743-8454-1-4
Abstract: Ascertainment was 100%. There had been 63 deaths, mainly of the most severely affected. The mean age of the 54 survivors was 35 years. The outcome in terms of disability ranged from apparent normality to total dependency. It reflected both the neurological deficit, which had been recorded in infancy in terms of sensory level, and events in the CSF shunt history. Overall about 2 in 5 of the survivors lived independently in the community, 2 in 5 drove a car, 1 in 5 was in competitive employment and 1 in 5 could walk 50 metres.Although those who survived to age 35 years tended to be less disabled, 2 in 5 continued to need daily care.Neurosurgical intervention in babies with open spina bifida had dramatic results in terms of survival. However, the disability and the complications of the survivors were often severe [1-5]. Many efforts were made to enable them to walk, to control their urinary incontinence while safeguarding renal function, and to overcome problems associated with the shunt treatment of hydrocephalus. Promising new methods of management, such as the psoas transplant, urinary diversion and artificial urinary sphincters, which seemed highly successful in the short term, lost favour after 10 or 15 years because of disappointing long-term results. In this unsteady course of progress it is helpful to have a long term follow up of a complete cohort of patients with open spina bifida as a realistic basis for helping parents facing the difficult decisions about termination of an affected pregnancy or treatment after birth.In 1963 the Regional Neurosurgical Unit at Addenbrooke's Hospital, Cambridge, England offered treatment to all cases of open spina bifida, without any attempt at selection. Between 1963 and 1971, after a detailed neurological examination, 117 babies (50 male, 67 female) had their open spinal defects closed within 48 hours of birth. A ventriculo-atrial cerebrospinal fluid (CSF) shunt was inserted for hydrocephalus when required.In 2002 all surviv
Lost in the Forest, Stuck in the Trees: Dispositional Global/Local Bias Is Resistant to Exposure to High and Low Spatial Frequencies
Gillian Dale, Karen M. Arnell
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098625
Abstract: Visual stimuli can be perceived at a broad, “global” level, or at a more focused, “local” level. While research has shown that many individuals demonstrate a preference for global information, there are large individual differences in the degree of global/local bias, such that some individuals show a large global bias, some show a large local bias, and others show no bias. The main purpose of the current study was to examine whether these dispositional differences in global/local bias could be altered through various manipulations of high/low spatial frequency. Through 5 experiments, we examined various measures of dispositional global/local bias and whether performance on these measures could be altered by manipulating previous exposure to high or low spatial frequency information (with high/low spatial frequency faces, gratings, and Navon letters). Ultimately, there was little evidence of change from pre-to-post manipulation on the dispositional measures, and dispositional global/local bias was highly reliable pre- to post-manipulation. The results provide evidence that individual differences in global/local bias or preference are relatively resistant to exposure to spatial frequency information, and suggest that the processing mechanisms underlying high/low spatial frequency use and global/local bias may be more independent than previously thought.
Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency
Gillian M. Schiralli Lester,Andrew J. Henderson
Molecular Biology International , 2012, DOI: 10.1155/2012/614120
Abstract: Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed. 1. Introduction A critical step in the HIV life cycle is transcriptional regulation of the integrated provirus. Robust transcription assures that sufficient mRNA and genomic RNA are produced for efficient virus assembly and infectivity. Repression of HIV transcription leads to the establishment of HIV latency, which creates repositories for infectious and drug-resistant viruses that reemerge upon treatment failure or interruption [1–4]. The existence of long-lived stable HIV reservoirs was demonstrated by the rebound of virus replication following highly active antiretroviral therapy (HAART) interruption [5–8]. These latent reservoirs, which include quiescent memory T cells, tissue-resident macrophages [9, 10], and potentially hematopoietic stem cells [11], although this is still controversial [12], represent long-lived subsets of cells with decreased or inactive proviral transcription. In general, studies with chronically and acutely infected cells show that mutations in Tat [13, 14], absence of cellular transcription factors [15–18], miRNA machinery [19, 20], and proviral integration into transcriptionally silent sites contribute to postintegration latency [21, 22]. Although there may not be a common mechanism that promotes HIV latency, it is critical to understand the molecular events that establish and maintain latency if strategies to reduce or purge HIV from latent reservoirs are to be devised [9, 23, 24]. HIV transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcriptional elongation, and chromatin organization. How these events are coordinated and their role in HIV latency will be reviewed. In particular, mechanisms that contribute to repressing HIV transcription will be highlighted. 2. LTR and Transcription Factors Although viral accessory proteins, such as Vpr, and putative elements within the HIV
Genetics and genomics of radiotherapy toxicity: towards prediction
Catharine M West, Gillian C Barnett
Genome Medicine , 2011, DOI: 10.1186/gm268
Abstract: Since the discovery of radiation at the end of the 19th century, radiotherapy has become one of the most important modalities for treating cancer. The schedules (total radiation dose, dose per fraction, number of fractions, overall treatment time and volume irradiated) have been developed to maximize tumor kill and minimize normal tissue damage. The radiation dose prescribed depends on the cancer type and surrounding normal tissue tolerance. Doses are generally given so that <5% of patients suffer serious toxicity up to 5 years following radiotherapy [1,2]. Serious side effects such as bowel obstruction and incontinence can occur months to years after treatment, be extremely debilitating and impact negatively on the quality-of-life of cancer survivors.Given the millions of cancer survivors worldwide, estimated at 2 million in the UK and 12 million in the USA, there is a need to increase our understanding of the molecular pathogenesis of radiotherapy toxicity, find ways of predicting those patients likely to suffer with long-term side effects, and develop new approaches for their amelioration. As there is a direct relationship between radiation dose and tumor control, the development of side effects in a minority limits the dose that can be safely prescribed to the majority of patients. Development of a test to predict those likely to suffer side effects should enable individualized radiation dose prescription to increase cancer cure while reducing the number of survivors suffering with the consequences of treatment.In this review, we outline the current radiotherapy approaches and understanding of how this treatment works. Then we discuss toxicity and the importance of genetics. We then focus on recent developments in identifying the genetic variants underlying radiosensitivity and the results from the first genome-wide association studies (GWASs), which suggested that a polymorphism in the follicle-stimulating hormone receptor (FSHR) gene might be associated with e
Epigenetic Targeting of Transforming Growth Factor β Receptor II and Implications for Cancer Therapy
Sanjib Chowdhury,Sudhakar Ammanamanchi,Gillian M. Howell
Molecular and Cellular Pharmacology , 2009,
Abstract: The transforming growth factor (TGF) β signaling pathway is involved in many cellular processes including proliferation, differentiation, adhesion, motility and apoptosis. The loss of TGFβ signaling occurs early in carcinogenesis and its loss contributes to tumor progression. The loss of TGFβ responsiveness frequently occurs at the level of the TGFβ type II receptor (TGFβRII) which has been identified as a tumor suppressor gene (TSG). In keeping with its TSG role, the loss of TGFβRII expression is frequently associated with high tumor grade and poor patient prognosis. Reintroduction of TGFβRII into tumor cell lines results in growth suppression. Mutational loss of TGFβRII has been characterized, particularly in a subset of colon cancers with DNA repair enzyme defects. However, the most frequent cause of TGFβRII silencing is through epigenetic mechanisms. Therefore, re-expression of TGFβRII by use of epigenetic therapies represents a potential therapeutic approach to utilizing the growth suppressive effects of the TGFβ signaling pathway. However, the restoration of TGFβ signaling in cancer treatment is challenging because in late stage disease, TGFβ is a pro-metastatic factor. This effect is associated with increased expression of the TGFβ ligand. In this Review, we discuss the mechanisms associated with TGFβRII silencing in cancer and the potential usefulness of histone deacetylase (HDAC) inhibitors in reversing this effect. The use of HDAC inhibitors may provide a unique opportunity to restore TGFβRII expression in tumors as their pleiotropic effects antagonize many of the cellular processes, which mediate the pro-metastatic effects associated with increased TGFβ expression.
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