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Search Results: 1 - 10 of 5626 matches for " Lynn Taylor "
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A Generalized Allosteric Mechanism for cis-Regulated Cyclic Nucleotide Binding Domains
Alexandr P. Kornev,Susan S. Taylor ,Lynn F. Ten Eyck
PLOS Computational Biology , 2008, DOI: 10.1371/journal.pcbi.1000056
Abstract: Cyclic nucleotides (cAMP and cGMP) regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB) domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels) using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1) the phosphate binding cassette (PBC), which binds the cAMP ribose-phosphate, 2) the “hinge,” a flexible helix, which contacts the PBC, 3) the β2,3 loop, which provides precise positioning of an invariant arginine from the PBC, and 4) a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif). The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the β2,3 loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP) represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains.
Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age
Auyeung Bonnie,Ahluwalia Jag,Thomson Lynn,Taylor Kevin
Molecular Autism , 2012, DOI: 10.1186/2040-2392-3-17
Abstract: Background Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children. Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old. Finding fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores. Conclusions These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.
Role of Us9 Phosphorylation in Axonal Sorting and Anterograde Transport of Pseudorabies Virus
Radomir Kratchmarov, Matthew P. Taylor, Lynn W. Enquist
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058776
Abstract: Alphaherpes viruses, such as pseudorabies virus (PRV), undergo anterograde transport in neuronal axons to facilitate anterograde spread within hosts. Axonal sorting and anterograde transport of virions is dependent on the viral membrane protein Us9, which interacts with the host motor protein Kif1A to direct transport. Us9-Kif1A interactions are necessary but not sufficient for these processes, indicating that additional cofactors or post-translational modifications are needed. In this study, we characterized two conserved serine phosphorylation sites (S51 and S53) in the PRV Us9 protein that are necessary for anterograde spread in vivo. We assessed the subcellular localization of phospho-Us9 subspecies during infection of neurons and found that the phospho-form is detectable on the majority, but not all, of axonal vesicles containing Us9 protein. In biochemical assays, phospho-Us9 was enriched in lipid raft membrane microdomains, though Us9 phosphorylation did not require prior lipid raft association. During infections of chambered neuronal cultures, we observed only a modest reduction in anterograde spread capacity for diserine mutant Us9, and no defect for monoserine mutants. Conversely, mutation of the kinase recognition sequence residues adjacent to the phosphorylation sites completely abrogated anterograde spread. In live-cell imaging analyses, anterograde transport of virions was reduced during infection with a recombinant PRV strain expressing GFP-tagged diserine mutant Us9. Phosphorylation was not required for Us9-Kif1A interaction, suggesting that Us9-Kif1A binding is a distinct step from the activation and/or stabilization of the transport complex. Taken together, our findings indicate that, while not essential, Us9 phosphorylation enhances Us9-Kif1A-based transport of virions in axons to modulate the overall efficiency of long-distance anterograde spread of infection.
Interferon-α Regulates Glutaminase 1 Promoter through STAT1 Phosphorylation: Relevance to HIV-1 Associated Neurocognitive Disorders
Lixia Zhao, Yunlong Huang, Changhai Tian, Lynn Taylor, Norman Curthoys, Yi Wang, Hamilton Vernon, Jialin Zheng
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032995
Abstract: HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN) α specifically activated the glutaminase 1 (GLS1) promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1) phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA levels in HIV associated-dementia (HAD) individuals correlate with STAT1 (p<0.01), IFN-α (p<0.05) and IFN-β (p<0.01). Together, these data indicate that both HIV-1 infection and IFN-α treatment increase glutaminase expression through STAT1 phosphorylation and by binding to the GLS1 promoter. Since glutaminase is a potential component of elevated glutamate production during the pathogenesis of HAND, our data will help to identify additional therapeutic targets for the treatment of HAND.
Racial differences in influenza vaccination among older americans 1996–2000: longitudinal analysis of the Health and Retirement Study (HRS) and the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey
Truls ?stbye, Donald H Taylor, Ann Marie M Lee, Gary Greenberg, Lynn van Scoyoc
BMC Public Health , 2003, DOI: 10.1186/1471-2458-3-41
Abstract: The purpose of the study was to determine whether frequencies of receipt vary by race, age group, gender, and time (progress from 1995/1996 to 2000), and whether any racial differences remain in age groups covered by Medicare. Subjects were selected from the Health and Retirement Study (HRS) (12,652 Americans 50–61 years of age (1992–2000)) and the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey (8,124 community-dwelling seniors aged 70+ years (1993–2000)). Using multivariate logistic regression, adjusting for potential confounders, we estimated the relationship between race, age group, gender, time and the main outcome measure, receipt of influenza vaccination in the last 2 years.There has been a clear increase in the unadjusted rates of receipt of influenza vaccination for all groups from 1995/1996 to 2000. However, the proportions immunized are 10–20% higher among White than among Black elderly, with no obvious narrowing of the racial gap from 1995/1996 to 2000. There is an increase in rates from age 50 to age 65. After age 70, the rate appears to plateau. In multivariate analyses, the racial difference remains after adjusting for a series of socioeconomic, health, and health care related variables. (HRS: OR = 0.63 (0.55–0.72), AHEAD: OR = 0.55 (0.44–0.66))There is much work left if the Healthy People 2010 goal of 90% of the elderly immunized against influenza annually is to be achieved. Close coordination between public health programs and clinical prevention efforts in primary care is necessary, but to be truly effective, these services must be culturally appropriate.Influenza frequently causes several days of incapacitating malaise for otherwise healthy individuals. In the elderly and persons with chronic medical conditions, it increases risk for serious complications and death. Twenty to 40 thousand deaths are attributed to influenza each year, with 90 percent of these in patients over age 65. [1] Influenza also has a large economic impact, in t
Structural and Thermal Properties of Tb, Ce Doped Y2.97Gd0.03Al2Ga3O12 Single Crystals  [PDF]
Mohammad Faheem, Kelvin Lynn
American Journal of Analytical Chemistry (AJAC) , 2014, DOI: 10.4236/ajac.2014.511078
Abstract: The structural and thermal properties of yttrium-aluminum-gadolinium-gallium (Y2.97Gd0.03Al2Ga3O12) single crystals doped with terbium (0.1%), cerium (0.01%) and co-doped with both terbium and cerium ((0.1, 0.01)%) were investigated. All samples were heated (calcined) at 1400°C for 15 hours before crystallization. X-ray powder diffraction (XRD) patterns of all calcined samples showed the presence of yttrium gallium aluminate (Y3Al2Ga3O12) and gadolinium gallium oxide (Gd3GaO6) while the grown crystals were single phase of Y3Al2Ga3O12. The lattice parameter of the crystals decreased with Ce doping. The thermal conductivity of each sample was determined from 25°C to 300°C and found to decrease exponentially with increasing temperature. All doped crystals have different thermal conductivity, which is attributed to the crucial influence of crystals structures. 0.01% Ce:YAGG was found to be a strong candidate for scintillators and other lasing materials because of its good thermal behavior (10.71 W/m·K).
Complexity of Interaction in a Second Language Conversation Group: An Exploratory Study  [PDF]
Melanie Lynn D’Amico
Open Journal of Modern Linguistics (OJML) , 2015, DOI: 10.4236/ojml.2015.54031
Abstract: The aim of this research was to explore the nature of conversation in a weekly second language Italian conversation group. Analysis of conversations focused on the range of topics and verbal structures used by learners. Additional analysis was completed to determine if learners engaged in negotiation of meaning or form during conversations. Results revealed that learners used a range of topics and verbal structures from Beginner level to Advanced level indicating that learners challenged themselves to produce high quality, natural conversation. Learners also showed some use of negotiation during conversations to repair communication breakdowns, principally to address meaning; however, the amount of negotiation was low when compared to task-based interaction designed to elicit negotiation.
PhosphoregDB: The tissue and sub-cellular distribution of mammalian protein kinases and phosphatases
Alistair RR Forrest, Darrin F Taylor, J Lynn Fink, M Milena Gongora, Cameron Flegg, Rohan D Teasdale, Harukazu Suzuki, Mutsumi Kanamori, Chikatoshi Kai, Yoshihide Hayashizaki, Sean M Grimmond
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-82
Abstract: The database lets users query where a specific kinase or phosphatase is expressed at both the tissue and sub-cellular levels. Similarly the interface allows the user to query by tissue, pathway or sub-cellular localization, to reveal which components are co-expressed or co-localized. A review of their expression reveals 30% of these components are detected in all tissues tested while 70% show some level of tissue restriction. Hierarchical clustering of the expression data reveals that expression of these genes can be used to separate the samples into tissues of related lineage, including 3 larger clusters of nervous tissue, developing embryo and cells of the immune system. By overlaying the expression, sub-cellular localization and classification data we examine correlations between class, specificity and tissue restriction and show that tyrosine kinases are more generally expressed in fewer tissues than serine/threonine kinases.Together these data demonstrate that cell type specific systems exist to regulate protein phosphorylation and that for accurate modelling and for determination of enzyme substrate relationships the co-location of components needs to be considered.It has been estimated that more than a third of all Eukaryotic proteins are subjected to phosphorylation [1]. The phosphorylation state of a protein can regulate functional properties including bioactivity, stability, sub-cellular localization, conformation and the ability to interact with other binding partners [2-6]. In mammals, several hundred kinases and phosphatases compete in a highly dynamic and spatially restricted fashion to control these post-translational modifications [7,8].For budding yeast 43 phosphatase and over 120 protein kinase like sequences [9] regulate processes such as cell cycle, DNA damage response, and signal transduction. For these organisms the network components of phospho-regulation are well defined and physically contained within one cell type however in multi-cellular
The Concentric Circle Revisited: Allocentrism and Self in a Contemporary Chinese Community  [PDF]
Weining C. Chang, Lynn Lee
Psychology (PSYCH) , 2012, DOI: 10.4236/psych.2012.34042
Abstract: Contemporary literature has extensively documented the connection between allocentrism and interdependence in self-construals. The present report comprises two studies that aimed to extend this literature by investigating the traditional Chinese concentric circle model of self-representation in a modern Asian community. Study 1 comprised a series of focus group discussions (N = 35, 4 males and 31 females, average age 20) to determine the qualitative content of self-construal. Participants reported a construct called the “true self”, with a content similar to the private self, and a number of social-selves varying along the perceived intimacy of the self-other relationship. In Study 2, 120 participants (all females, average age 19) were tested on their level of allocentrism and then allocated to an allocentric (top 25%, N = 30) and an idiocentric (bottom 25%; N = 30) group. Participants responded to the Twenty-Self Statement-Test (TST) on seven relationship scenarios with various levels of intimacy. Their responses were coded into collective/private/public self categories. Allocentrism and scenarios were found to have main and interactive effects on the proportions of self categories. The results were interpreted as supporting the graded nature of Chinese self-other relationships and a modified concentric circle self-representation in modern Asia.
Examining the Relationship between Hope and Attachment: A Meta-Analysis  [PDF]
John Blake, Christine Lynn Norton
Psychology (PSYCH) , 2014, DOI: 10.4236/psych.2014.56065
Abstract:

The authors report quantitative findings from a meta-analysis of studies investigating the relationship between attachment style, grounded in theory developed by Bowlby and Ainsworth; and Snyder’s theoretical model of hope (Ainsworth & Bowlby, 1991; Snyder, 1994). Statistically significant results provide support for further investigation of clinical value of the attachment/hope dynamic as an effective heuristic for conceptualizing human development, behavior and the therapeutic process.

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