Unexpected false feelings of familiarity about faces are associated with increased pupil dilations

Our subjective sense that something we encounter is familiar to us is reflected by changes in pupil size. Although pupil dilation effects of familiarity have been well documented, familiarity is not the only, or even the strongest, contributing factor to pupil dilation. Changes in pupil dilation also reflect changes in brightness, affective or emotional responses, hormonal release, expected value or utility, and surprise, among others. Because many factors can affect pupil dilation, important questions remain about how pupil dilation changes reflect high-order cognitive processes, like attention and memory. For example, because surprise and familiarity are often difficult to fully distinguish (since new experiences can be surprising or unexpected), it can be difficult to tease apart pupil dilation effects of surprise versus familiarity. To better understand the effects of surprise and familiarity on pupil dilation, we examined pupil responses during a recognition memory task involving photographs of faces and outdoor scenes. When participants rated novel face images as “familiar,” we observed a robust pupil dilation response.

Metabolic and endocrine changes in acute and chronic critical illness

Critical illness, an extreme form of severe physical stress, is characterized by important endocrine and metabolic changes. The development of critical care medicine has made possible survival from conditions that were previously rapidly fatel, and as a result many patients now enter a prolonged phase of chronic or persistent critical illness. Acute endocrine adaptations are directed towards providing energy and substrates for the vital fight or flight response in the context of exogenous substrate deprivation. Distinct endocrine and metabolic alterations characterize the chronic phase of critical illness, which seems to no longer be solely beneficial and may hamper recovery and rehabilitation. Onset of the stressful event causes an acute activation of pulsatile hormonal release from the anterior pituitary, followed by suppression in the chronic phase of illness, ultimately resolving to normality if recovery occurs.

Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation

The human dopamine transporter(hDAT) plays a major role in dopamine homeostasis and regulation of neurotransmission by clearing dopamine from the extracellular space using secondary active transport. Dopamine is an essential monoamine chemical messenger that regulates reward seeking behavior, motor control, hormonal release, and emotional response in humans. Psychostimulants such as cocaine primarily target the central binding site of hDAT and lock the transporter in an outward-facing conformation, thereby inhibiting dopamine reuptake. The inhibition of dopamine reuptake leads to accumulation of dopamine in the synapse causing heightened signaling. In addition, hDAT is implicated in various neurological disorders and disease-associated neurodegeneration. Despite its significance, the molecular architecture of hDAT and its various conformational states are poorly understood. Instability of hDAT in detergent micelles has been a limiting factor in its successful biochemical, biophysical, and structural characterization. To overcome this hurdle, first we identified ligands that stabilize hDAT in detergent micelles. Then, we screened ∼200 single residue mutants of hDAT using high-throughput scintillation proximity assay, and identified a thermostable variant(I248Y). Here we report a robust strategy to overexpress and successfully purify a thermostable variant of hDAT in an inhibitor and allosteric ligand bound conformation.

Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (<xref ref-type="bibr" rid="bib3">Barhanin et al., 1996</xref>; <xref ref-type="bibr" rid="bib57">Sanguinetti et al., 1996</xref>), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (<xref ref-type="bibr" rid="bib77">Wrobel et al., 2012</xref>; <xref ref-type="bibr" rid="bib66">Sun et al., 2012</xref>; <xref ref-type="bibr" rid="bib1">Abbott, 2014</xref>). These changes are essential for the physiological role of IKs (<xref ref-type="bibr" rid="bib62">Silva and Rudy, 2005</xref>); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.

Small G Proteins Dexras1 and RHES and Their Role in Pathophysiological Processes

Dexras1 and RHES, monomeric G proteins, are members of small GTPase family that are involved in modulation of pathophysiological processes. Dexras1 and RHES levels are modulated by hormones and Dexras1 expression undergoes circadian fluctuations. Both these GTPases are capable of modulating calcium ion channels which in turn can potentially modulate neurosecretion/hormonal release. These two GTPases have been reported to prevent the aberrant cell growth and induce apoptosis in cell lines. Present review focuses on role of these two monomeric GTPases and summarizes their role in pathophysiological processes.