Two motivational bases for not contributing to a public good, desire to free ride (or greed) and fear of being a "sucker," were experimentally compared; 110 Japanese undergraduates served as subjects. It was hypothesized that these two types of motivation would be activated under different situations. When a public good was provided conjunctively, fear would have a strong effect but greed would not; when a public good was disjunctively provided, greed would have a strong effect but fear would not. In addition, this prediction was expected to hold when subjects are total strangers, and that the greater mutual trust existing among friends would make them contribute more than strangers would in the conjunctive condition but would make no difference in the disjunctive condition. Three types of "production rules," in which a public good is conjunctively, disjunctively, or additively produced on the basis of members' contributions, were experimentally created. Half of the groups in each condition consisted of total strangers, and the other half consisted of friends. The hypotheses were supported when the size of the public good (bonus points) was relatively large. Also, subjects responded similarly in the conjunctive condition and in the additive condition.

Several theories of emotion propose that emotional responses are largely determined by the way events are appraised. To determine whether the proposed dimensions of appraisal are consistent across cultures, 973 Ss from the United States, Japan, Hong Kong, and the People's Republic of China were asked to describe emotional experiences. Few differences between the 3 cultures were observed on the more primitive dimensions (pleasantness, attentional activity, certainty, coping ability, and goal/need conduciveness) and on 2 of the more cognitively complex dimensions (legitimacy and norm/self compatibility). More substantial differences were observed on 3 other complex dimensions (control, responsibility, and anticipated effort). Considerable pan-cultural consistency was also observed in the dimensions of subjective experience of emotion and in the relations between these dimensions and cognitive appraisals.

No abstract

Since 1995, more than 100 transgenic (Tg) mouse models of Alzheimer’s disease (AD) have been generated in which mutant amyloid precursor protein (APP) or APP/presenilin 1 (PS1) cDNA is overexpressed (1st generation models). Although many of these models successfully recapitulate major pathological hallmarks of the disease such as amyloid β peptide (Aβ) deposition and neuroinflammation, they have suffered from artificial phenotypes in the form of overproduced or mislocalized APP/PS1 and their functional fragments, as well as calpastatin deficiency-induced early lethality, calpain activation, neuronal cell death without tau pathology, endoplasmic reticulum stresses, and inflammasome involvement. Such artifacts bring two important uncertainties into play, these being (1) why the artifacts arise, and (2) how they affect the interpretation of experimental results. In addition, destruction of endogenous gene loci in some Tg lines by transgenes has been reported. To overcome these concerns, single App knock-in mouse models harboring the Swedish and Beyreuther/Iberian mutations with or without the Arctic mutation (AppNL–G–F and AppNL–F mice) were developed (2nd generation models). While these models are interesting given that they exhibit Aβ pathology, neuroinflammation, and cognitive impairment in an age-dependent manner, the model with the Artic mutation, which exhibits an extensive pathology as early as 6 months of age, is not suitable for investigating Aβ metabolism and clearance because the Aβ in this model is resistant to proteolytic degradation and is therefore prone to aggregation. Moreover, it cannot be used for preclinical immunotherapy studies owing to the discrete affinity it shows for anti-Aβ antibodies. The weakness of the latter model (without the Arctic mutation) is that the pathology may require up to 18 months before it becomes sufficiently apparent for experimental investigation. Nevertheless, this model was successfully applied to modulating Aβ pathology by genome editing, to revealing the differential roles of neprilysin and insulin-degrading enzyme in Aβ metabolism, and to identifying somatostatin receptor subtypes involved in Aβ degradation by neprilysin. In addition to discussing these issues, we also provide here a technical guide for the application of App knock-in mice to AD research. Subsequently, a new double knock-in line carrying the AppNL–F and Psen1P117L/WT mutations was generated, the pathogenic effect of which was found to be synergistic. A characteristic of this 3rd generation model is that it exhibits more cored plaque pathology and neuroinflammation than the AppNL–G–F line, and thus is more suitable for preclinical studies of disease-modifying medications targeting Aβ. Furthermore, a derivative AppG–F line devoid of Swedish mutations which can be utilized for preclinical studies of β-secretase modifier(s) was recently created. In addition, we introduce a new model of cerebral amyloid angiopathy that may be useful for analyzing amyloid-related imaging abnormalities that can be caused by anti-Aβ immunotherapy. Use of the App knock-in mice also led to identification of the α-endosulfine-KATP channel pathway as components of the somatostatin-evoked physiological mechanisms that reduce Aβ deposition via the activation of neprilysin. Such advances have provided new insights for the prevention and treatment of preclinical AD. Because tau pathology plays an essential role in AD pathogenesis, knock-in mice with human tau wherein the entire murine Mapt gene has been humanized were generated. Using these mice, the carboxy-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) was discovered as a mediator linking tau pathology to neurodegeneration and showed that tau humanization promoted pathological tau propagation. Finally, we describe and discuss the current status of mutant human tau knock-in mice and a non-human primate model of AD that we have successfully created.

. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295: H677-H690, 2008. First published June 13, 2008 doi:10.1152/ajpheart.91519.2007.-Heterozygous bone morphogenetic protein receptor-II-knockout (BMPR2 ϩ/Ϫ ) mice have a similar genetic trait like that in some idiopathic pulmonary arterial hypertension patients. To examine the effect of pulmonary endothelial injury in BMPR2ϩ/Ϫ mice, we challenged the mice with two injections of monocrotaline combined with intratracheal instillation of replicationdeficient adenovirus expressing 5-lipoxygenase (MCTϩAd5LO). After the challenge (1 wk), BMPR2 ϩ/Ϫ mice exhibited a doubling of right ventricular systolic pressure that was greater than that of wildtype mice and remained elevated for 3 wk before heart failure developed. Muscularization and thickening of small pulmonary arterioles was evident in the BMPR2 ϩ/Ϫ lungs at 2 wk after the challenge and became severe at 3 wk. Marked perivascular infiltration of T cells, B cells, and macrophages was associated with the remodeled vessels. Real-time PCR analysis showed that the expression of six endothelial cell markers in lung tissue was decreased to 20 -40% of original levels at 1 wk after the challenge in both BMPR2ϩ/Ϫ and wild-type mice and largely recovered in wild-type (50 -80%) but not BMPR2 ϩ/Ϫ lungs (30 -50%) at 3 wk after the challenge. Macrophage inflammatory protein-1␣ and fractalkine receptor expression doubled in BMPR2ϩ/Ϫ compared with wild-type lungs. Expression of type I and type II BMP receptors, but not transforming growth factor-␤ receptors, in the challenged BMPR2 ϩ/Ϫ and wild-type lungs showed a similar pattern of expression as that of endothelial markers. Apoptotic responses at 1 wk after MCT and Ad5LO challenge were also significantly greater in the BMPR2 ϩ/Ϫ lungs than the wild-type lungs. These data show that BMPR2 ϩ/Ϫ mice are more sensitive to MCTϩAd5LO-induced pulmonary hypertension than wild-type mice. Greater endothelial injury and an enhanced inflammatory response could be the underlying causes of the sensitivity and may work in concert with BMPR2 heterozygosity to promote the development of persistent pulmonary hypertension.heterozygous bone morphogenetic protein receptor-2 knockout mice HETEROZYGOUS GERMLINE MUTATIONS of bone morphogenetic protein receptor-2 (BMPR2) have been found in patients with idiopathic pulmonary arterial hypertension (IPAH) (10,20,46), a progressive disease characterized by extensive remodeling of the pulmonary arterioles and persistent increase of pulmonary artery pressure of unknown cause. Nearly 70% of familial IPAH and 20% of sporadic IPAH patients have a heterozygous BMPR2 mutation (1), but the chance of developing pulmonary arterial hypertension (PAH) among the BMPR2 mutant family members is only 10 -20% (32). Therefore, additional factors are believed to be required for the development of PAH in the BMPR2 mutant carriers.The BMPR2 gene encodes BMPR-II, which forms a complex with ...

Field-effect transistors (FETs) based on [6]phenacene thin films were fabricated with SiO2 and parylene gate dielectrics. These FET devices exhibit field-effect mobility in the saturation regime as high as 7.4 cm(2) V(-1) s(-1), which is one of the highest reported values for organic thin-film FETs. The two- and four-probe mobilities in the linear regime display nearly similar values, suggesting negligible contact resistance at 300 K. FET characteristics were investigated using two-probe and four-probe measurement modes at 50-300 K. The two-probe mobility of the saturation regime can be explained by the multiple shallow trap and release model, while the intrinsic mobility obtained by the four-probe measurement in the linear regime is better explained by the phenomenon of transport with charge carrier scattering at low temperatures. The FET device fabricated with a parylene gate dielectric on polyethylene terephthalate possesses both transparency and flexibility, implying feasibility of practical application of [6]phenacene FETs in flexible/transparent electronics. N-channel FET characteristics were also achieved in the [6]phenacene thin-film FETs using metals that possess a small work function for use as source/drain electrodes.

4 suggesting that CMYA3 is directly regulated by Ang II signaling. This gene, since named Xirp2 (also known as mXin␤ and myomaxin), is a direct target of the MEF2A transcription factor and is markedly downregulated in hearts lacking MEF2A. 5,6 Xirp2 belongs to the ancient, muscle-specific, actin-binding Xin gene family whose expression can be traced to ancestral vertebrates with a 2-chambered heart. 7-9 Xirp2 is expressed in cardiac and skeletal muscle where it interacts with filamentous actin and ␣-actinin through the novel actin-binding motif, the Xin repeat. 5,8 In striated muscle, Xirp2 localizes to the peripheral Z-disc region, or costamere, 5 and the intercalated disk. 10,11 The subcellular localization of Xirp2 is significant in that the costamere and intercalated disk harbor mechanical stress sensors that are critical for normal muscle function. [12][13][14] Antisense knockdown of Xin in developing chick embryos, the sole Xin family member in this species, results in a severe disruption of cardiac looping morphogenesis. 9 In mice, a lossof-function mutation of mXin␣, the mammalian ortholog of Xin, results in cardiomyopathy and conduction defects. 11 In the present study we sought to determine the role of Xirp2 in cardiac development and/or function. Mice harboring a hypomorphic Xirp2 allele are viable but display cardiac hypertrophy. As Xirp2 is regulated by Ang II, we also examined cardiac pathology in hypomorphic mice with long-term administration of this hormone. In contrast to wild type mice exposed to a chronic Ang II infusion, hypomorphic mice displayed diminished cardiac hypertrophy, fibrosis, and apoptosis. Furthermore, we demonstrate that regulation of Xirp2 gene expression in response to Ang II signaling is mediated by MEF2A. Our results suggest that Original

These results suggest that contact inhibition after the proliferation stage may induce growth arrest via cell-cell communication through the expression of CDKI p21 and may be responsible for progressing cell fusion.