In This Issue

Abstract

In This Issue Emotional signs of approaching depressionComplex systems approaching a tipping point typically experience a period called "critical slowing down, " in which the system's resilience and recovery from perturbations slow prior to a change in state. To assess whether such critical slowdown precedes a shift between healthy and depressed emotional states, Ingrid van de analyzed studies in which volunteers recorded their emotions at random times over 5 or 6 days. The authors focused on reports provided by 535 emotionally healthy and 93 depressed volunteers that monitored four emotions: cheerful, content, sad, and anxious. For volunteers who experienced a change of emotional health after the study, whether into or out of depression, the authors report that previous positive or negative emotions better predicted future similar emotions than for volunteers whose emotional health did not change. Negative emotions appeared to be reinforced in persons progressing toward depression; likewise, positive emotions appeared to be reinforced in persons progressing out of depression. Emotional variance during the study was also high for volunteers approaching a change. The authors suggest that the trends in emotional correlation and variance are indicative of an increase in emotional inertia and critical slowdown leading to a tipping point. Such signs may serve as an early-warning system for the onset of depression, according to the authors. -P.G.

Solution structure of an ultra-stable single-chain insulin analog connects protein dynamics to a novel mechanism of receptor binding

“…The product of a single gene, the IR precursor is processed in the trans-Golgi network to form a disulfide-linked (␣␤) 2 homodimer (14). The extracellular ␣ subunits bind insulin, and the transmembrane ␤ subunits contain the intracellular TK domains (15). Whereas the structure of the holoreceptor has been visualized only at low resolution (Ͼ20 Å (16)), its domain dissection has enabled stepwise crystallographic analysis.…”

“…(ii) The structure of the N-terminal three domains of the ␣ subunit (Leu-rich domain 1, Cysrich domain, and Leu-rich domain 2; L1-CR-L2) has been determined at 2.3 Å (19). (iii) The structure of the dimeric ectodomain ((␣␤ ⌬ ) 2 , containing the entire ␣ subunit and the extracellular portion of the ␤ subunit, ␤ ⌬ ) has been determined at 3.3 Å (20), wherein its conformation resembles an inverted V. Although co-crystals of an insulin-ectodomain complex have not been obtained, a variety of evidence indicates that insulin binds within the crux of the dimer (15,21,22).…”

“…Construction of domain-minimized models of the IR ␣ subunit has enabled crystallization of "micro-receptor" (IR) complexes (15,21). Such complexes contain, at a minimum, the primary insulin-binding elements L1 and ␣CT stabilized by an Fab antibody fragment.…”

“…Such complexes contain, at a minimum, the primary insulin-binding elements L1 and ␣CT stabilized by an Fab antibody fragment. One such co-crystal structure, determined at 3.5 Å resolution, depicted a ternary complex between insulin, an L1-CR fragment, and a synthetic ␣CT peptide spanning residues 704 -719 of IR isoform A (15). In this structure the C-terminal segment of the insulin B chain pivots from the hormone's ␣-helical core to enable its insertion between the conserved surfaces of L1 and the ␣CT peptide.…”

Impact of monoolein on aquaporin1-based supported lipid bilayer membranes

“…A flat DOPC/MO SLB can be observed except for a few defects in figure 2(H). As DOPC exhibits a lower phase transition temperature (−18 ± 1 °C) than DPPC [24, 25], DOPC vesicles are in the liquid crystal phase. It has been reported that liquid crystal phase phospholipid vesicles can form an SLB with few defects [26–28].…”