Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

MTF-1-Mediated Repression of the Zinc Transporter Zip10 Is Alleviated by Zinc Restriction

The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10 expression decreased in response to zinc repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A cells also respond differentially to zinc availability in vitro. Measurement of Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was transcriptionally regulated by zinc deficiency. Through luciferase promoter constructs and ChIP analysis, binding of MTF-1 to a metal response element located 17 bp downstream of the transcription start site was shown to be necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1 causes down-regulation of Zip10 transcription by physically blocking Pol II movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of hepatocytes and neuro 2A cells. Collectively, these results reveal a novel repressive role for MTF-1 in the regulation of the Zip10 zinc transporter expression by pausing Pol II transcription. ZIP10 may have roles in control of zinc homeostasis in specific sites particularly those of the brain and liver. Within that context ZIP10 may act as an important survival mechanism during periods of zinc inadequacy

Nurses' experiences, expectations, and preferences for mind-body practices to reduce stress

BACKGROUND: Most research on the impact of mind-body training does not ask about participants\u27 baseline experience, expectations, or preferences for training. To better plan participant-centered mind-body intervention trials for nurses to reduce occupational stress, such descriptive information would be valuable. METHODS: We conducted an anonymous email survey between April and June, 2010 of North American nurses interested in mind-body training to reduce stress. The e-survey included: demographic characteristics, health conditions and stress levels; experiences with mind-body practices; expected health benefits; training preferences; and willingness to participate in future randomized controlled trials. RESULTS: Of the 342 respondents, 96% were women and 92% were Caucasian. Most (73%) reported one or more health conditions, notably anxiety (49%); back pain (41%); GI problems such as irritable bowel syndrome (34%); or depression (33%). Their median occupational stress level was 4 (0 = none; 5 = extreme stress). Nearly all (99%) reported already using one or more mind-body practices to reduce stress: intercessory prayer (86%), breath-focused meditation (49%), healing or therapeutic touch (39%), yoga/tai chi/qi gong (34%), or mindfulness-based meditation (18%). The greatest expected benefits were for greater spiritual well-being (56%); serenity, calm, or inner peace (54%); better mood (51%); more compassion (50%); or better sleep (42%). Most (65%) wanted additional training; convenience (74% essential or very important), was more important than the program\u27s reputation (49%) or scientific evidence about effectiveness (32%) in program selection. Most (65%) were willing to participate in a randomized trial of mind-body training; among these, most were willing to collect salivary cortisol (60%), or serum biomarkers (53%) to assess the impact of training. CONCLUSIONS: Most nurses interested in mind-body training already engage in such practices. They have greater expectations about spiritual and emotional than physical benefits, but are willing to participate in studies and to collect biomarker data. Recruitment may depend more on convenience than a program\u27s scientific basis or reputation. Knowledge of participants\u27 baseline experiences, expectations, and preferences helps inform future training and research on mind-body approaches to reduce stress

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways

Nonlinear control by input-output state variable feedback pole assignment

This paper considers pole assignment control of nonlinear dynamic systems described by State Dependent Paramete (SDP) models. The approach follows from earlier research into linear Proportional-Integral-Plus (PIP) methods but, in SDP system control, the control coefficients are updated at each sampling instant on the basis of the latest SDP relationships. Alternatively, algebraic solutions can be derived off-line to yield a practically useful control algorithm that is relatively straightforward to implement on a digital computer, requiring only the storage of delayed system variables, coupled with straightforward arithmetic expressions in the control software. Although the analysis is limited to the case when the open-loop system has no zeros, time delays are handled automatically. The paper shows that the closed-loop system reduces to a linear transfer function with the specified (design) poles. Hence, assuming pole assignability at each sample, global stability of the nonlinear system is guaranteed at the design stage