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Sex crime in subways poses an ever-present threat to Japanese commuters. This paper proposes a simple and viable adjunct to the current tactics by harnessing the potential of the watching eyes effect to deter sexual harassment. It attempts to observe the human biological sensitivity to gaze and to explore its application to the specific Japanese context where powerful informal control exists. The paper also identifies the possible advantages and limitations of such measure, with the goal of stimulating more discussion over evidence-based behavioural interventions in deterring crimes. A tentative proposal is composed to summarize and demonstrate a number of behaviourally informed suggestions regarding the practical implementation and configuration of the proposed measure.

We thought we knew all we needed to about the tumor suppressor p53. However, Yoon et al. now describe a previously unrecognized function of p53 (see the Perspective by Zitvogel and Kroemer). p53 induces expression of the gene encoding DD1α, a receptor-like transmembrane protein of the immunoglobulin superfamily. In conditions of stress, p53 activation can lead to cell death. p53-induced expression of DD1α also promotes the clearance of dead cells by promoting engulfment by macrophages. Furthermore, expression of DD1α on T cells inhibits T cell function. Thus, p53 offers protection from inflammatory disease caused by the accumulation of apoptotic cells, and its suppression of T cells might help cancer cells to escape immune detection. Science , this issue 10.1126/science.1261669 ; see also p. 476 p53 promotes clearance of dead cells and proper immune function. [Also see Perspective by Zitvogel and Kroemer ] The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1 α ( DD1 α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1 α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.

The Ser/Thr Rho kinase 1 (ROCK1) is known to have major roles in a wide range of cellular activities, including those involved in tumour metastasis and apoptosis. Here we identify an indispensable function of ROCK1 in metabolic stress-induced autophagy. Applying a proteomics approach, we characterize Beclin1, a proximal component of the phosphoinositide 3-kinase class III lipid–kinase complex that induces autophagy, as an interacting partner of ROCK1. Upon nutrient deprivation, activated ROCK1 promotes autophagy by binding and phosphorylating Beclin1 at Thr119. This results in the specific dissociation of the Beclin1–Bcl-2 complex without affecting the Beclin1–UVRAG interaction. Conversely, inhibition of ROCK1 activity increases Beclin1–Bcl-2 association, thus reducing nutritional stress-mediated autophagy. Genetic knockout of ROCK1 function in mice also leads to impaired autophagy as evidenced by reduced autophagosome formation. These results show that ROCK1 acts as a prominent upstream regulator of Beclin1-mediated autophagy and maintains a homeostatic balance between apoptosis and autophagy. The kinase ROCK1 has been implicated in apoptosis and other cellular functions. Here Gurkar et al . show that ROCK1 phosphorylates the autophagy regulator Beclin1, which activates autophagy by disrupting the association between Beclin-1 and Bcl-2.

Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme responsible for the biosynthesis of monounsaturated fatty acids (MUFAs). MUFAs are important substrates for the synthesis of various kinds of lipids that are essential to many key biological functions. Therefore, determining the regulation of SCD is critical to the understanding of its role in different biological pathways. SCD1 isoform is primarily regulated at the level of gene transcription by many transcription factors, and identification of certain transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), has implicated a role of SCD1 in lipid metabolism. Subsequent studies with SCD1 deficient (SCD1-/-) mice further demonstrated an important role for SCD1 in lipid metabolism. To further explore the role of SCD1 in lipid metabolism, transcriptional regulation of SCD1 gene by the nuclear receptor liver X receptor (LXR) was investigated. LXRs are important regulators of cholesterol and lipid homeostasis. Regulation of SCD1 gene by LXR was presumed to be primarily mediated by the master regulator of fatty acid synthesis SREBP-1c. However, here we demonstrated that SCD1 gene is also regulated by direct transcriptional activation by LXR through an LXR response element identified in the 5' promoter region of SCD1 gene. SCD1-/- mice were then employed to study the effect of SCD1 deficiency on LXR agonist T0901317-induced accumulation of hepatic and plasma triglyceride. Upon T0901317-mediated LXR activation, SCD1-/- mice had reduced hepatic triglyceride accumulation and were markedly protected against plasma accumulation of triglyceride-rich very-low density lipoproteins (VLDLs). Further studies demonstrated that SCD1 deficiency did not reduce T0901317-induced secretion of large, triglyceride-rich VLDLs. However, SCD1 deficiency did modulate the MUFA and saturated fatty acid (SFA) content of the triglycerides packaged onto the VLDLs, resulting in the attenuation of the T0901317-induced increase of MUFA to SFA ratio. This suggests that under T0901317-mediated LXR activation, SCD1-/- mice produce triglyceride-rich VLDL particles that are MUFA-poor or SFA-rich and may then protect against plasma triglyceride-rich VLDL accumulation by possibly increasing VLDL catabolism. Together, these studies contribute to the understanding of the role of SCD1 in lipid metabolism and, more importantly, begin to shed light on its role in VLDL metabolism.

Objective: Mood stabilizers have been reported to affect brain concentrations of myo-inositol (mI) and N-acetylaspartate (NAA). We examined the effects of quetiapine (QUET), an atypical antipsychotic, on these neurochemicals, and potential predictors of response to QUET in adolescents with bipolar depression. Methods: Twenty-six adolescents with bipolar depression participated in an 8-week placebo-controlled trial of QUET monotherapy. Subjects were scanned at baseline and after 8 weeks with proton magnetic resonance spectroscopy (1H-MRS) at 3T and 4T at two sites, with 8 cm3 voxels placed in the right and left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). LCModel was used to calculate absolute concentrations of NAA and mI. Results: Twenty-six subjects had pre- and posttreatment scans (mean age=15.6 years, 9 boys). Of these subjects, 5 out of 16 subjects receiving QUET and 5 out of 10 receiving placebo (PBO) were responders (50% decrease in Children's Depression Rating Scale [CDRS] score). Although baseline ACC mI did not predict responder status, responders had significantly lower posttreatment ACC mI values than did nonresponders (3.27±.71 vs. 4.23±.70; p=0.004). There were no significant differences in the changes in ACC and DLPFC NAA levels in the QUET group compared with the PBO group (ACC: −0.55±1.3 vs.+0.25±1.5, p=0.23; right-DLPFC: −0.55±1.3 vs. 0.33±0.89, p=0.13; left-DLPFC: −0.04±0.91 vs.+0.29±0.61, p=0.41). Conclusion: We found that posttreatment, not baseline, ACC mI levels were associated with response to QUET in adolescents with bipolar depression. There were no differences in NAA concentration changes between the QUET and PBO groups. Larger studies including different brain regions would help to clarify the effects of QUET on neurochemistry in patients with bipolar disorder.