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Search Results: 1 - 10 of 401627 matches for " Gina M. Story "
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Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura
Huang Dongyue,Li Shuyang,Dhaka Ajay,Story Gina M
Molecular Pain , 2012, DOI: 10.1186/1744-8069-8-66
Abstract: Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM8-expressing neurons are virtually absent in the dural afferent population, nor do these neurons cluster around dural afferent neurons. Taken together, our results suggest that TRPV1 and TRPA1 but not TRPM8 channels likely contribute to the excitation of dural afferent neurons and the subsequent activation of the headache circuit. These results provide an anatomical basis for understanding further the functional significance of TRP channels in headache pathophysiology.
Comparative Effects of Heterologous TRPV1 and TRPM8 Expression in Rat Hippocampal Neurons
Devon C. Crawford,Krista L. Moulder,Robert W. Gereau IV,Gina M. Story,Steven Mennerick
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008166
Abstract: Heterologous channel expression can be used to control activity in select neuronal populations, thus expanding the tools available to modern neuroscience. However, the secondary effects of exogenous channel expression are often left unexplored. We expressed two transient receptor potential (TRP) channel family members, TRPV1 and TRPM8, in cultured hippocampal neurons. We compared functional expression levels and secondary effects of channel expression and activation on neuronal survival and signaling. We found that activation of both channels with appropriate agonist caused large depolarizing currents in voltage-clamped hippocampal neurons, exceeding the amplitude responses to a calibrating 30 mM KCl stimulation. Both TRPV1 and TRPM8 currents were reduced but not eliminated by 4 hr incubation in saturating agonist concentration. In the case of TRPV1, but not TRPM8, prolonged agonist exposure caused strong calcium-dependent toxicity. In addition, TRPV1 expression depressed synaptic transmission dramatically without overt signs of toxicity, possibly due to low-level TRPV1 activation in the absence of exogenous agonist application. Despite evidence of expression at presynaptic sites, in addition to somatodendritic sites, TRPM8 expression alone exhibited no effects on synaptic transmission. Therefore, by a number of criteria, TRPM8 proved the superior choice for control over neuronal membrane potential. This study also highlights the need to explore potential secondary effects of long-term expression and activation of heterologously introduced channels.
Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1
Lillian Cruz-Orengo, Ajay Dhaka, Robert J Heuermann, Timothy J Young, Michael C Montana, Eric J Cavanaugh, Donghee Kim, Gina M Story
Molecular Pain , 2008, DOI: 10.1186/1744-8069-4-30
Abstract: Our search for endogenous chemical activators utilizing a bioactive lipid library screen identified a cyclopentane PGD2 metabolite, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), as a TRPA1 agonist. Similar to CA and AITC, this electrophilic molecule is known to modify cysteines of cellular target proteins. Electophysiological recordings verified that 15d-PGJ2 specifically activates TRPA1 and not TRPV1 or TRPM8 (thermoTRPs also enriched in DRG). Accordingly, we identified a population of mouse DRG neurons responsive to 15d-PGJ2 and AITC that is absent in cultures derived from TRPA1 knockout mice. The irritant molecules that activate TRPA1 evoke nociceptive responses. However, 15d-PGJ2 has not been correlated with painful sensations; rather, it is considered to mediate anti-inflammatory processes via binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ). Our in vivo studies revealed that 15d-PGJ2 induced acute nociceptive responses when administered cutaneously. Moreover, mice deficient in the TRPA1 channel failed to exhibit such behaviors.In conclusion, we show that 15d-PGJ2 induces acute nociception when administered cutaneously and does so via a TRPA1-specific mechanism.The prostaglandins (PGs) are a class of biomolecules derived from arachidonic acid (AA) that are involved in a variety of signaling processes including inflammation. For example, PGE2 and PGI2 are produced during inflammation and contribute to the direct sensitization of nociceptive neurons of the dorsal root ganglia (DRG). Downstream of binding to its G protein-coupled receptor (GPCR), PGE2 sensitizes nociceptive neurons to thermal stimuli via PKA-dependent phosphorylation of the heat- and capsaicin-gated Transient Receptor Potential (TRP) ion channel TRPV1 [1]. TRPV1 is the founding mammalian member of a subfamily of TRP channels gated by temperature (dubbed thermoTRPs)[2].TRPA1, first characterized as a thermoTRP channel gated by noxious cold (although this finding is con
The Physiological Response during Divergent Thinking  [PDF]
Gareth H. Loudon, Gina M. Deininger
Journal of Behavioral and Brain Science (JBBS) , 2016, DOI: 10.4236/jbbs.2016.61004
Abstract: Our research studied the physiological response of participants during a creative task to investigate if a person’s psychophysiological state was correlated with divergent thinking performance. We used heart rate variability as our physiological measure. We asked 50 participants to perform a cognitive task that assessed their divergent thinking skills and recorded their heart rate and heart rate variability (HRV) before and during the task. Frequency domain analysis was performed on the HRV. The results showed that there was a significant negative correlation between log-transformed low frequency HRV power and the number of “divergent thinking” words generated. Our results suggest that a person’s psychophysiological state is correlated with their divergent thinking performance, and that attention and motivation may be important factors, however this needs further research. Our findings also suggest that being in a relaxed state before the start of a creative task is not a predictor of creative performance.
The Physiological Response to Drawing and Its Relation to Attention and Relaxation  [PDF]
Gareth H. Loudon, Gina M. Deininger
Journal of Behavioral and Brain Science (JBBS) , 2017, DOI: 10.4236/jbbs.2017.73011
Abstract: The main purpose of this study was to analyze the physiological response of participants during a creative activity and compare the results to their physiological response during states of high attention and relaxation. Our interest was not only about the relationship between creativity and attention, but also about the role of valence and arousal. We used heart rate variability (HRV) as our physiological measure. We asked twenty-two participants to undertake three activities: a stroop test; a relaxation activity; and a drawing activity. After each activity, the participants were asked to reflect on their levels of attention, relaxation and enjoyment. The results showed significant physiological differences between the three activities: mean heart rate, F(2, 42) = 8.96, p = 0.001; log-transformed low frequency HRV power, F(1.43, 30.07) = 18.12, p < 0.001; and log-transformed high frequency HRV power, F(2, 42) = 6.25, p = 0.004. Overall, the results suggested that participants had high levels of attention during the drawing activity, with positive valence. The results also suggested that participants’ levels of arousal differed between the three activities. The implications of these results are described in the discussion.
Introduction: Puerto Ricans in Chicago
Gina M. Pérez
Centro Journal , 2001,
An upbeat west side story: Puerto Ricans and postwar racial politics in Chicago
Gina M. Pérez
Centro Journal , 2001,
Abstract: Chicago Puerto Ricans have inhabited a number of ideological positions since their arrival en asse in the late 1940s, ranging from their short-lived tenure as the city's "model" minority in the 1950s and 1960s and, eventually, to their membership in urban America's alleged "culture of poverty" and "underclass". Using historical and ethnographic data, this article analyzes the different ways in which Chicago Puerto Ricans have been portrayed and imagined differently over time; explores the role of the state in constructing and disseminating particular constructions of Puerto Rican migrants in Chicago; and demonstrates how varying constructions of Puerto Ricans are related to both their shifting location in Chicago's political economy as well as their relationship vis-à-vis ethnic and racial and ethnic Others in the city.
Type I insulin-like growth factor receptor over-expression induces proliferation and anti-apoptotic signaling in a three-dimensional culture model of breast epithelial cells
Gina M Yanochko, Walter Eckhart
Breast Cancer Research , 2006, DOI: 10.1186/bcr1392
Abstract: Pooled, stable MCF-10A breast epithelial cells expressing wild-type IGFIR or kinase-dead IGFIR (K1003A) were generated using retroviral-mediated gene transfer. The effects of over-expression of wild-type or kinase-dead IGFIR on breast epithelial cell biology were analyzed by confocal microscopy of three-dimensional cultures. The contribution of signaling pathways downstream of IGFIR activation to proliferation and apoptosis were determined by pharmacological inhibition of phosphatidylinositol 3' kinase (PI3K) with LY294002, MAP kinase kinase (MEK) with UO126 and mammalian target of rapamycin (mTOR) with rapamycin.We found that MCF-10A cells over-expressing the IGFIR formed large, misshapen acinar structures with filled lumina and disrupted apico-basal polarization. This phenotype was ligand-dependent, occurring with IGF-I or supraphysiological doses of insulin, and did not occur in cells over-expressing the kinase-dead receptor. We observed increased proliferation, decreased apoptosis and increased phosphorylation of Ser473 of Akt and Ser2448 of mTOR throughout IGFIR structures. Inhibition of PI3K with LY294002 or MEK with UO126 prevented the development of acinar structures from IGFIR-expressing but not control cells. The mTOR inhibitor rapamycin failed to prevent IGFIR-induced hyperproliferation and survival signaling.Increased proliferation and survival signaling as well as loss of apico-basal polarity by IGFIR activation in mammary epithelial cells may promote early lesions of breast cancer. Three-dimensional cultures of MCF-10A cells over-expressing the IGFIR are a useful model with which to study the role of IGFIR signaling in breast cancer progression and for characterizing the effects of chemotherapeutics targeted to IGFIR signaling.Cycles of proliferation and invasion followed by massive apoptosis are central to the physiology of the mammary gland. The branching ductal architecture develops postnatally in response to hormone stimulation during puberty, but
Retrospective Assessments of Childhood Psychopathology by Adults and Their Parents  [PDF]
Frederick L. Coolidge, Gina M. Tambone, Robert L. Durham, Daniel L. Segal
Psychology (PSYCH) , 2011, DOI: 10.4236/psych.2011.23026
Abstract: The present study compared retrospective personality and psychopathological assessments of adults about their childhood and adolescence with concurrent assessments by one of their parents. One-hundred three college stu-dents (Mage = 23.1 years) and one of their parents (Mage = 51.2 years) completed a retrospective version of the 200-item, parent-as-respondent, Coolidge Personality and Neuropsychological Inventory (R-CPNI). The median internal scale reliabilities (Cronbach’s α) for all 46 scales of the R-CPNI were substantial for the adult retrospec-tive (α = 0.78) and the parent retrospective versions (α = 0.79), and there was a strong correlation between the adult and parent retrospective scale reliabilities (r = 0.88). To evaluate group differences, t tests revealed that the parent means were significantly lower than the adult means on 45 of the 46 scales with mostly large effect sizes. Principal components analyses of the scales for both adult and parent retrospective versions were strongly and positively correlated (r = 0.88) for the total number of components extracted. These findings appear to support the contention that retrospective assessments tend to be reliable and valid and that parents’ retrospective recol-lections of their children’s psychopathology tend to be more positive than the retrospective reports by the adults. Based on these preliminary findings, it appears that the R-CPNI may provide a unique and interesting tool for the retrospective measurement of psychopathology.
Choice of population structure informative principal components for adjustment in a case-control study
Gina M Peloso, Kathryn L Lunetta
BMC Genetics , 2011, DOI: 10.1186/1471-2156-12-64
Abstract: We found that when the SNP and phenotype frequencies do not vary over the sub-populations, all methods of selection provided similar power and appropriate Type I error for association. When the SNP is not structured and the phenotype has large structure, then selection methods that do not select PCs for inclusion as covariates generally provide the most power. When there is a structured SNP and a non-structured phenotype, selection methods that include PCs in the model have greater power. When both the SNP and the phenotype are structured, all methods of selection have similar power.Standard practice is to include a fixed number of PCs in genome-wide association studies. Based on our findings, we conclude that if power is not a concern, then selecting the same set of top PCs for adjustment for all SNPs in logistic regression is a strategy that achieves appropriate Type I error. However, standard practice is not optimal in all scenarios and to optimize power for structured SNPs in the presence of unstructured phenotypes, PCs that are associated with the tested SNP should be included in the logistic model.The principal components (PCs) of genome-wide genotype data can be used to detect and adjust for population structure in genetic association analyses [1,2]. The popularity of the PC method is evident by its wide use: it has been cited by over 400 publications. However, the choice of which PCs to use and the best way to adjust for the PCs in analyses of dichotomous traits is not yet clear.Numerous methods have been proposed to adjust for structure once PCs are computed (Table 1). The simplest and most straightforward approach is to adjust for continuous PCs in a regression model. Kimmel et al [3] note that principal component analysis (PCA) is sufficient for identifying population structure, but adjusting for PCs as covariates in a model may not always eliminate false positive associations since the PCs are only an estimate of the population structure. Furthermore, Yu
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