Neuronal Representations of Reference-dependent Value

計畫編號：MOST 102-2420-H032-002-MY2研究期間：20130101~20140630[[abstract]]How does a person assess the outcome of a choice? Kőszegi and Rabin (2006) proposed a reference-dependent utility theory in which the overall utility of an outcome is composed of two components: an intrinsic consumption utility attached to the choice itself and a gain-loss utility which is reference dependent. Using functional magnetic resonance imaging, we investigated the way people weigh consumption utility and gain-loss utility to assess an outcome. Trials in Session 1 were to monitor neural responses to multiple types of money-food reward bundles. Trials in Session 2 comprised an initial expectancy phase, when rewards in each bundle were not fully disclosed and needed to be predicted, and a subsequent outcome phase, when actual amounts of rewards were revealed. We found that mPFC and OFC track expected consumption utility for money-food rewards bundles. Generally, reference-dependent experienced utility was also observed in the same regions. mPFC also encodes gain or loss signals that were computed during experience of actual rewards.[[sponsorship]]行政院科技部[[notice]]補正完

Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII

Regulation of intracellular cyclic adenosine 3’, 5’-monophosphate (cAMP) by multiple pathways enables differential function of this ubiquitous second messenger in a context dependent manner. Modulation of Gs-stimulated intracellular cAMP has long been known to be modulated by the Gi and Gq/Ca2+ pathways. Recently, the G13 pathway was also shown to facilitate cAMP responses in murine macrophage cells. We report here that this synergistic regulation of cAMP synthesis by the Gs and G13 pathways is mediated by a specific isoform of adenylyl cyclase, AC7. Furthermore, this signaling paradigm exists in several hematopoietic lineages and can be recapitulated by exogenous expression of AC7 in HEK 293 cells. Mechanistic characterization of this synergistic interaction indicates that it occurs downstream of receptor activation and it can be mediated by the alpha subunit of either G12 or G13. Our results demonstrate that AC7 is a specific downstream effector of the G12/13 pathway

Coherence of an optically illuminated single nuclear spin qubit

We investigate the coherence properties of individual nuclear spin quantum bits in diamond [Dutt et al., Science, 316, 1312 (2007)] when a proximal electronic spin associated with a nitrogen-vacancy (NV) center is being interrogated by optical radiation. The resulting nuclear spin dynamics are governed by time-dependent hyperfine interaction associated with rapid electronic transitions, which can be described by a spin-fluctuator model. We show that due to a process analogous to motional averaging in nuclear magnetic resonance, the nuclear spin coherence can be preserved after a large number of optical excitation cycles. Our theoretical analysis is in good agreement with experimental results. It indicates a novel approach that could potentially isolate the nuclear spin system completely from the electronic environment.Comment: 5 pages, 2 figure

Interactions of EGF, Wnt and HOM-C genes specify the P12 neuroectoblast fate in C. elegans

We investigate how temporal and spatial interactions between multiple intercellular and intracellular factors specify the fate of a single cell in Caenorhabditis elegans. P12, which is a ventral cord neuroectoblast, divides postembryonically to generate neurons and a unique epidermal cell. Three classes of proteins are involved in the specification of P12 fate: the LIN-3/LET-23 epidermal growth factor signaling pathway, a Wnt protein LIN-44 and its candidate receptor LIN-17, and a homeotic gene product EGL-5. We show that LIN-3 is an inductive signal sufficient to promote the P12 fate, and the conserved EGF signaling pathway is utilized for P12 fate specification; egl-5 is a downstream target of the lin-3/let-23 pathway in specifying P12 fate; and LIN-44 and LIN-17 act synergistically with lin-3 in the specification of the P12 fate. The Wnt pathway may function early in development to regulate the competence of the cells to respond to the LIN-3 inductive signal

Nurse-led cognitive screening model for older adults in primary care

Author version made available in accordance with publisher copyright. Under 12 month embargo from date of publication [26 September 2014]. This is the accepted version of the following article: [Yang, Y., Xiao, L. D., Deng, L., Wang, Y., Li, M. and Ullah, S. (2014), Nurse-led cognitive screening model for older adults in primary care. Geriatrics & Gerontology International.], which has been published in final form at [doi: 10.1111/ggi.12339]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery.Aim The present study aimed to establish a nurse-led cognitive screening model for community-dwelling older adults with subjective memory complaints from seven communities in Chongqing, China, and report the findings of this model. Methods Screenings took place from July 2012 to June 2013. Cognitive screening was incorporated into the annual health assessment for older adults with subjective memory complaints in a primary care setting. Two community nurses were trained to implement the screening using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results Of 733 older adults, 495 (67.5%) reported having subjective memory complaints. Of the 249 individuals who participated in the cognitive screening, 102 (41%) had mild cognitive impairment, whereas 32 (12.9%) had cognitive impairment. A total of 80 participants (78.4%) with mild cognitive impairment agreed to participate in a memory support program. Participants with cognitive impairment were referred to specialists for further examination and diagnosis; only one reported that he had seen a specialist and had been diagnosed with dementia. Conclusions Incorporating cognitive screening into the annual health assessment for older adults with subjective memory complaints was feasible, though referral rates from primary care providers remained unchanged. The present study highlights the urgent need for simple screenings as well as community-based support services in primary care for older adults with cognitive or mild cognitive impairments

Use of a cAMP BRET Sensor to Characterize a Novel Regulation of cAMP by the Sphingosine 1-Phosphate/G13 Pathway

Regulation of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) is integral in mediating cell growth, cell differentiation, and immune responses in hematopoietic cells. To facilitate studies of cAMP regulation we developed a BRET (bioluminescence resonance energy transfer) sensor for cAMP, CAMYEL (cAMP sensor using YFP-Epac-RLuc), which can quantitatively and rapidly monitor intracellular concentrations of cAMP in vivo. This sensor was used to characterize three distinct pathways for modulation of cAMP synthesis stimulated by presumed Gs-dependent receptors for isoproterenol and prostaglandin E2. Whereas two ligands, uridine 5'-diphosphate and complement C5a, appear to use known mechanisms for augmentation of cAMP via Gq/calcium and Gi, the action of sphingosine 1-phosphate (S1P) is novel. In these cells, S1P, a biologically active lysophospholipid, greatly enhances increases in intracellular cAMP triggered by the ligands for Gs-coupled receptors while having only a minimal effect by itself. The enhancement of cAMP by S1P is resistant to pertussis toxin and independent of intracellular calcium. Studies with RNAi and chemical perturbations demonstrate that the effect of S1P is mediated by the S1P2 receptor and the heterotrimeric G13 protein. Thus in these macrophage cells, all four major classes of G proteins can regulate intracellular cAMP

The mediating role of cultural intelligence to learning flexibility, cultural difference and expatriate effectiveness

PurposeDrawing on experiential learning theory, this study seeks to understand how the perceived cultural difference in a foreign country and learning flexibility, which enables more integrated experiential learning from international experience, influence expatriates’ cultural intelligence (CQ) and consequently their adjustment and job performance.Design/methodology/approachSurvey data were collected from 169 expatriates in China. Polynomial regression analyses were employed to test curvilinear relationships between cultural difference and CQ and between learning flexibility and CQ. Mediation hypotheses were tested either by the MEDCURVE procedure if a curvilinear relationship was confirmed or by the Haye’s Process procedure if a curvilinear relationship was not confirmed and instead a linear relationship was confirmed.FindingsThe results demonstrated a positive relationship between cultural difference and CQ and an inverted U-shape relationship between learning flexibility and CQ. CQ mediated the relationship between cultural difference and expatriate adjustment and partially mediated the relationship between learning flexibility and expatriate adjustment. CQ positively influenced expatriates’ job performance via expatriate adjustment.Practical implicationsOur findings suggest that companies should not hesitate to send expatriates on assignments to culturally very different countries and focus more attention on the selection of expatriates. The findings of this study suggest firms should choose candidates who are moderate or high in learning flexibility and could engage in integrated learning and specialized learning in a more balanced manner.Originality/valueThis research is the first study that examines the influence of learning flexibility on CQ and expatriate effectiveness. It examines cultural difference through the lens of experiential learning theory and argues that cultural difference constitutes “stimuli” in the experiential learning environment for individual learning in an international context. The results advance our knowledge of the role of experiential learning in developing capable global managers.</jats:sec

Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits.

ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the suppressive histone mark H3K27me3 is significantly reduced upon the loss of ATRX. We conclude that the ablation of ATRX in excitatory forebrain neurons leads to sexually dimorphic effects on miR-137 expression and on spatial memory, identifying a potential therapeutic target for neurological defects caused by ATRX dysfunction

Deciphering Signaling Outcomes from a System of Complex Networks

Cellular signal transduction machinery integrates information from multiple inputs to actuate discrete cellular behaviors. Interaction complexity exists when an input modulates the output behavior that results from other inputs. To address whether this machinery is iteratively complex—that is, whether increasing numbers of inputs produce exponential increases in discrete cellular behaviors—we examined the modulated secretion of six cytokines from macrophages in response to up to five-way combinations of an agonist of Toll-like receptor 4, three cytokines, and conditions that activated the cyclic adenosine monophosphate pathway. Although all of the selected ligands showed synergy in paired combinations, few examples of nonadditive outputs were found in response to higher-order combinations. This suggests that most potential interactions are not realized and that unique cellular responses are limited to discrete subsets of ligands and pathways that enhance specific cellular functions