Balanced Synaptic Input Shapes the Correlation between Neural Spike Trains

Stimulus properties, attention, and behavioral context influence correlations between the spike times produced by a pair of neurons. However, the biophysical mechanisms that modulate these correlations are poorly understood. With a combined theoretical and experimental approach, we show that the rate of balanced excitatory and inhibitory synaptic input modulates the magnitude and timescale of pairwise spike train correlation. High rate synaptic inputs promote spike time synchrony rather than long timescale spike rate correlations, while low rate synaptic inputs produce opposite results. This correlation shaping is due to a combination of enhanced high frequency input transfer and reduced firing rate gain in the high input rate state compared to the low state. Our study extends neural modulation from single neuron responses to population activity, a necessary step in understanding how the dynamics and processing of neural activity change across distinct brain states

Psychosocial variables associated with colorectal cancer screening in South Australia

Background: Population screening reduces mortality from colorectal cancer, yet factors associated with uptake of screening are incompletely understood. Purpose: The purpose of the study was to determine demographic and psychosocial factors associated with participation in faecal occult blood test (FOBT)-based colorectal cancer (CRC) screening in an average risk community programme in Adelaide, South Australia. Method: A questionnaire consistent with the Preventive Health Model was used to determine demographic and psychosocial differences between previous FOBT-based screening participants (n = 413, response rate 93.2%) and non-participants (n = 481, response rate 47.9%). Results were analysed by univariate and multivariate generalised linear modelling, and factors associated with participation were identified. Results: Factor analysis of psychosocial items revealed an optimal three-factor solution (knowledge, faecal aversion, belief in the value of screening). Following multivariate analyses, two psychosocial and two demographic factors remained as predictors of FOBT screening behaviour: (1) items related to faecal aversion (Aversion), relative risk (RR) = 0.61, CI = 0.55–0.69, (2) perceptions about the value of screening (Value), RR = 1.45, CI = 1.13–1.85, (3) age band 65–69 (Age, five age bands, relative to age 50–54), RR = 1.43, CI = 1.16–1.76 and FOBT type (Test; three tests, Hemoccult®, FlexSure®, InSure® randomly assigned, relative to Hemoccult®: FlexSure®: RR = 1.41, CI = 1.17–1.71, InSure®: RR = 1.76, CI = 1.47–2.11. Conclusions: The psychosocial factors associated with non-participation in FOBT-based CRC screening are amenable to interventions designed to improve participation. The small relative risks values associated with each predictor, however, raise the possibility that additional factors are likely to influence screening participation.Stephen R. Cole, Ian Zajac, Tess Gregory, Sarah Mehaffey, Naomi Roosa, Deborah Turnbull, Adrian Esterman, Graeme P. Youn

Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors

The transcription factor GATA-1 and its cofactor FOG-1 are essential for the normal development of erythroid cells and megakaryocytes. FOG-1 can stimulate or inhibit GATA-1 activity depending on cell and promoter context. How the GATA-1–FOG-1 complex controls the expression of distinct sets of gene in megakaryocytes and erythroid cells is not understood. Here, we examine the molecular basis for the megakaryocyte-restricted activation of the αIIb gene. FOG-1 stimulates GATA-1-dependent αIIb gene expression in a manner that requires their direct physical interaction. Transcriptional output by the GATA-1–FOG-1 complex is determined by the hematopoietic Ets protein Fli-1 that binds to an adjacent Ets element. Chromatin immunoprecipitation experiments show that GATA-1, FOG-1 and Fli-1 co-occupy the αIIb promoter in vivo. Expression of several additional megakaryocyte-specific genes that bear tandem GATA and Ets elements in their promoters also depends on the physical interaction between GATA-1 and FOG-1. Our studies define a molecular context for transcriptional activation by GATA-1 and FOG-1, and may explain the occurrence of tandem GATA and Ets elements in the promoters of numerous megakaryocyte-expressed genes