A Neural Circuit Covarying with Social Hierarchy in Macaques

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals'' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals'' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.     

Prion Protein-mediated Toxicity of Amyloid-β Oligomers Requires Lipid Rafts and the Transmembrane LRP1

Soluble oligomers of the amyloid-β (Aβ) peptide cause neurotoxicity, synaptic dysfunction, and memory impairments that underlie Alzheimer disease (AD). The cellular prion protein (PrP^C) was recently identified as a high affinity neuronal receptor for Aβ oligomers. We report that fibrillar Aβ oligomers recognized by the OC antibody, which have been shown to correlate with the onset and severity of AD, bind preferentially to cells and neurons expressing PrP^C. The binding of Aβ oligomers to cell surface PrP^C, as well as their downstream activation of Fyn kinase, was dependent on the integrity of cholesterol-rich lipid rafts. In SH-SY5Y cells, fluorescence microscopy and co-localization with subcellular markers revealed that the Aβ oligomers co-internalized with PrP^C, accumulated in endosomes, and subsequently trafficked to lysosomes. The cell surface binding, internalization, and downstream toxicity of Aβ oligomers was dependent on the transmembrane low density lipoprotein receptor-related protein-1 (LRP1). The binding of Aβ oligomers to cell surface PrP^C impaired its ability to inhibit the activity of the β-secretase BACE1, which cleaves the amyloid precursor protein to produce Aβ. The green tea polyphenol (−)-epigallocatechin gallate and the red wine extract resveratrol both remodeled the fibrillar conformation of Aβ oligomers. The resulting nonfibrillar oligomers displayed significantly reduced binding to PrP^C-expressing cells and were no longer cytotoxic. These data indicate that soluble, fibrillar Aβ oligomers bind to PrP^C in a conformation-dependent manner and require the integrity of lipid rafts and the transmembrane LRP1 for their cytotoxicity, thus revealing potential targets to alleviate the neurotoxic properties of Aβ oligomers in AD.     

Impact of internal and external factors on prosocial choices in rhesus macaques

While traditional economic models assume that agents are self-interested, humans and most non-human primates are social species. Therefore, many of decisions they make require the integration of information about other social agents. This study asks to what extent information about social status and the social context in which decisions are taken impact on reward-guided decisions in rhesus macaques. We tested 12 monkeys of varying dominance status in several experimental versions of a two-choice task in which reward could be delivered to self only, only another monkey, both the self and another monkey, or neither. Results showed dominant animals were more prone to make prosocial choices than subordinates, but only when the decision was between a reward for self only and a reward for both self and other. If the choice was between a reward for self only and a reward for other only, no animal expressed altruistic behaviour. Finally, prosocial choices were true social decisions as they were strikingly reduced when the social partner was replaced by a non-social object. These results showed that as in humans, rhesus macaques'' social decisions are adaptive and modulated by social status and the cost associated with being prosocial.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.     

1981～2000年陕西省植被净初级生产力时空变化

为阐明陕西省植被净初级生产力(NPP)变化的整体状况,应用以遥感观测数据驱动的GLO-PEM模式模拟估计的NPP数据,对陕西省1981~2000年间的地表植被净初级生产力的空间分布及时间序列变化进行了综合分析.研究结果表明:(1)20年来,陕西省年NPP变化范围为687~858 g/(m2?a),平均值为749 g/(m2?a);(2)陕西省年平均NPP在波动中缓慢上升,NPP年增长幅度为3.248 2 g/(m2?a);(3)陕西省年平均NPP分布总体呈现从南到北递减的趋势,长城沿线风沙区NPP在200~400 g/(m2?a)之间,是陕西省NPP最低的地区;关中中东部NPP较高,大部在800 g/(m2?a)以上,NPP在1 200 g/(m2?a)以上的面积约占1/3,是全省NPP的高值区;(4)陕西省NPP基本不变(NPP变化百分率在-10%~10%之间)的面积占54.7%,NPP变化百分率增加10%以上的面积占40.5%,NPP变化百分率降低10%以下的面积仅占4.8%;(5)占陕西省总面积的77.3%的区域NPP变化不显著(P>0.05),NPP增加极显著(P<0.01)的区域占8.3%,增加显著(P<0.05)的区域占13.8%,NPP降低显著(P<0.05)和降低极显著(P<0.01)占0.7%.     

Counterfactual choice and learning in a neural network centered on human lateral frontopolar cortex

Decision making and learning in a real-world context require organisms to track not only the choices they make and the outcomes that follow but also other untaken, or counterfactual, choices and their outcomes. Although the neural system responsible for tracking the value of choices actually taken is increasingly well understood, whether a neural system tracks counterfactual information is currently unclear. Using a three-alternative decision-making task, a Bayesian reinforcement-learning algorithm, and fMRI, we investigated the coding of counterfactual choices and prediction errors in the human brain. Rather than representing evidence favoring multiple counterfactual choices, lateral frontal polar cortex (lFPC), dorsomedial frontal cortex (DMFC), and posteromedial cortex (PMC) encode the reward-based evidence favoring the best counterfactual option at future decisions. In addition to encoding counterfactual reward expectations, the network carries a signal for learning about counterfactual options when feedback is available-a counterfactual prediction error. Unlike other brain regions that have been associated with the processing of counterfactual outcomes, counterfactual prediction errors within the identified network cannot be related to regret theory. Furthermore, individual variation in counterfactual choice-related activity and prediction error-related activity, respectively, predicts variation in the propensity to switch to profitable choices in the future and the ability to learn from hypothetical feedback. Taken together, these data provide both neural and behavioral evidence to support the existence of a previously unidentified neural system responsible for tracking both counterfactual choice options and their outcomes.     

Antagonist-mediated down-regulation of toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus

IntroductionPrevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence.MethodsProtein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA.ResultsFor subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells.ConclusionsIn conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response.