Network dynamics of human face perception.

Prevailing theories suggests that cortical regions responsible for face perception operate in a serial, feed-forward fashion. Here, we utilize invasive human electrophysiology to evaluate serial models of face-processing via measurements of cortical activation, functional connectivity, and cortico-cortical evoked potentials. We find that task-dependent changes in functional connectivity between face-selective regions in the inferior occipital (f-IOG) and fusiform gyrus (f-FG) are bidirectional, not feed-forward, and emerge following feed-forward input from early visual cortex (EVC) to both of these regions.

Surface-based mixed effects multilevel analysis of grouped human electrocorticography.

Electrocorticography (ECoG) in humans yields data with unmatched spatio-temporal resolution that provides novel insights into cognitive operations. However, the broader application of ECoG has been confounded by difficulties in accurately depicting individual data and performing statistically valid population-level analyses. To overcome these limitations, we developed methods for accurately registering ECoG data to individual cortical topology.

Mineralocorticoid receptor antagonizes Dot1a-Af9 complex to increase αENaC transcription.

Aldosterone is a major regulator of Na(+) absorption and acts by activating the mineralocorticoid receptor (MR) to stimulate the epithelial Na(+) channel (ENaC). MR(-/-) mice exhibited pseudohypoaldosteronism type 1 (hyponatremia, hyperkalemia, salt wasting, and high levels of aldosterone) and died around postnatal day 10. However, if and how MR regulates ENaC transcription remain incompletely understood.

Aldosterone reprograms promoter methylation to regulate αENaC transcription in the collecting duct.

Aldosterone increases tubular Na(+) absorption largely by increasing α-epithelial Na(+) channel (αENaC) transcription in collecting duct principal cells. How aldosterone reprograms basal αENaC transcription to high-level activity in the collecting duct is incompletely understood. Promoter methylation, a covalent but reversible epigenetic process, has been implicated in the control of gene expression in health and disease.

Sp1 trans-activates and is required for maximal aldosterone induction of the αENaC gene in collecting duct cells.

The epithelial Na+ channel (ENaC) in the distal nephron constitutes the rate-limiting step for renal sodium reabsorption. Aldosterone increases tubular sodium absorption in large part by increasing αENaC transcription in collecting duct principal cells. We previously reported that Af9 binds to +78/+92 of αENaC and recruits Dot1a to repress basal and aldosterone-sensitive αENaC transcription in mouse inner medullary collecting duct (mIMCD)3 cells.

Network interneurons underlying ciliary locomotion in Hermissenda.

In the nudibranch mollusk Hermissenda, ciliary locomotion contributes to the generation of two tactic behaviors. Light elicits a positive phototaxis, and graviceptive stimulation evokes a negative gravitaxis. Two classes of light-responsive premotor interneurons in the network contributing to ciliary locomotion have been recently identified in the cerebropleural ganglia.

Serotonin regulates voltage-dependent currents in type I(e(A)) and I(i) interneurons of Hermissenda.

Serotonin (5-HT) has both direct and modulatory actions on central neurons contributing to behavioral arousal and cellular-synaptic plasticity in diverse species. In Hermissenda, 5-HT produces changes in intrinsic excitability of different types of identified interneurons in the circumesophageal nervous system. Using whole cell patch-clamp techniques we have examined membrane conductance changes produced by 5-HT that contribute to intrinsic excitability in two identified classes of interneurons, types I(i) and I(eA).

Sensory regulation of network components underlying ciliary locomotion in Hermissenda.

Ciliary locomotion in the nudibranch mollusk Hermissenda is modulated by the visual and graviceptive systems. Components of the neural network mediating ciliary locomotion have been identified including aggregates of polysensory interneurons that receive monosynaptic input from identified photoreceptors and efferent neurons that activate cilia. Illumination produces an inhibition of type I(i) (off-cell) spike activity, excitation of type I(e) (on-cell) spike activity, decreased spike activity in type III(i) inhibitory interneurons, and increased spike activity of ciliary efferent neurons.

Does coronary vasodilation after adenosine override endothelin-1-induced coronary vasoconstriction?

Endothelin-1 is a powerful coronary vasoconstrictor that is overexpressed in coronary artery disease. Adenosine is a powerful coronary vasodilator used for myocardial perfusion imaging to identify flow-limiting coronary artery stenosis. Therefore, in an animal model we tested the hypothesis that intracoronary endothelin-1 may cause myocardial perfusion abnormalities by positron emission tomography (PET) at resting conditions that may persist or only partially improve after intravenous adenosine stress in the absence of myocardial scar and flow-limiting stenosis.

Role of mTOR signaling in intestinal cell migration.

An early signaling event activated by amino acids and growth factors in many cell types is the phosphorylation of the mammalian target of rapamycin (mTOR; FRAP), which is functionally linked to ribosomal protein s6 kinase (p70(s6k)), a kinase that plays a critical regulatory role in the translation of mRNAs and protein synthesis. We previously showed that intestinal cell migration, the initial event in epithelial restitution, is enhanced by l-arginine (ARG). In this study, we used amino acids as prototypic activators of mTOR and ARG, IGF-1, or serum as recognized stimulators of intestinal cell migration.

Activation of PPARgamma enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats.

It is suggested that insulin resistance and metabolic maladaptation of the heart are causes of contractile dysfunction. We tested the hypothesis whether systemic PPARgamma activation, by changing the metabolic profile in a model of insulin resistance and type 2 diabetes (the ZDF rat) in vivo, improves contractile function of the heart in vitro. Male Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats, at 53-56 days of age, were treated with either GI-262570 (a nonthiazolidinedione PPARgamma agonist; A) or vehicle (V) for 1 wk.

Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes.

Moderate alcohol consumption has been shown to reduce the morbidity and mortality from coronary heart disease. Ethanol elicits its protective effects via mechanisms that include activation of protein kinases linked to growth and survival. Our results in isolated neonatal rat cardiomyocytes demonstrate that repeated short-term, low-dose exposure to ethanol is sufficient to activate the growth and/or survival pathways that involve PKC-epsilon, Akt, and AMP-activated kinase.

In vivo expression profile of a H+-K+-ATPase alpha2-subunit promoter-reporter transgene.

Because little is known about the molecular basis of transcriptional regulation of the murine H(+)-K(+)-ATPase alpha(2) (HKalpha(2)) gene or other genes whose expression is restricted in part to the collecting duct, especially in vivo, we developed transgenic mice carrying an insertional HKalpha(2) promoter-reporter gene construct. In these mice, the region -7,264/+253 of the HKalpha(2) 5'-flanking region controls expression of the reporter gene enhanced green fluorescent protein (EGFP). Patterns of HKalpha(2)/EGFP transgene expression were examined by fluorescence microscopy and immunoblotting.

Olympic goal: molecular and cellular approaches to understanding muscle adaptation.

Skeletal muscle is a plastic tissue showing adaptations to training that permit more physical work with less fatigue. Delineation of basic mechanisms of these adaptations will allow the development of scientifically based programs of exercise as well as potential new drugs for the maintenance of physical fitness.

Gastrointestinal disruption: the hazard of nonoperative management in adults with blunt abdominal injury.

The danger inherent to nonoperative management of patients with blunt abdominal injury is that gastrointestinal disruptions will escape timely diagnosis and repair. However, children with blunt abdominal injury have been successfully treated nonoperatively for more than a decade. It has been recently proposed, based upon small series, that adults can be managed nonoperatively in a manner similar to that for children.