γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status

The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication.     

Nonhuman primate neuroimaging and cocaine medication development.

Given the important role of the dopamine transporter (DAT) in the addictive properties of cocaine, the development and use of compounds that target the DAT represents a reasonable approach for the pharmacological treatment of cocaine abuse. The present report describes a series of studies conducted in nonhuman primates that evaluated the effectiveness of DAT inhibitors in reducing cocaine self-administration. In addition, drug substitution studies evaluated the abuse liability of the DAT inhibitors. Positron emission tomography neuroimaging studies quantified DAT occupancy at behaviorally relevant doses, characterized the time-course of drug uptake in brain, and documented drug-induced changes in cerebral blood flow as a model of brain activation. Selective DAT inhibitors were effective in reducing cocaine use but high (>70%) levels of DAT occupancy were associated with significant reductions in cocaine self-administration. The selective DAT inhibitors were reliably self-administered but rates of responding were lower than those maintained by cocaine even at higher levels of DAT occupancy. A profile of slow rate of drug uptake in brain accompanied by a gradual increase in extracellular dopamine may account for the more limited reinforcing effectiveness of the DAT inhibitors. Selective serotonin transporter (SERT) inhibitors were also effective in reducing cocaine use and blocked cocaine-induced brain activation and increases in extracellular dopamine. Coadministration of SERT inhibitors with a selective DAT inhibitor was more effective than the DAT inhibitor administered alone, even at comparable levels of DAT occupancy. The results indicate that combined inhibition of DAT and SERT may be a viable approach to treat cocaine addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Domestic dogs (Canis familiaris) use human gestures but not nonhuman tokens to find hidden food.

The authors examined the ability of domestic dogs to use human body cues (gestures) and equivalent-sized nonhuman cues to find hidden food in an object choice paradigm. In Experiment 1 the authors addressed the importance of the human element of the cue, and the effects of size, topography, and familiarity on dogs' success in using cues. Experiment 2 further explored the role of the human as cue-giver, and the impact of a change in the experimenter's attentional state during cue presentation. This included a systematic test of the role inanimate tokens play as cues apart from human placement. Our results indicate that dogs are more sensitive to human cues than equivalent nonhuman cues, and that the size of the cue is a critical element in determining dogs' success in following it. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects on executive function following damage to the prefrontal cortex in the rhesus monkey (Macaca mulatta).

[Correction Notice: An erratum for this article was reported in Vol 123(3) of Behavioral Neuroscience (see record 2009-07961-027). There was an error in the first sentence of the third full paragraph in the text on p. 235. The sentence should read “Based on the lesion reconstructions it was determined, as intended, that all monkeys had complete damage to areas 46, 8a, 8b, 9 and slight damage to area 10.”] Executive function is a term used to describe the cognitive processes subserved by the prefrontal cortex (PFC). An extensive body of work has characterized the effects of damage to the PFC in nonhuman primates, but it has focused primarily on the capacity of recognition and working memory. One limitation in studies of the functional parcellation of the PFC has been the absence of tests that assess executive function or its functional components. The current study used an adaptation of the Wisconsin Card Sorting Test, a classic test of frontal lobe and executive function in humans, to assess the effects of bilateral lesions in the dorsolateral PFC on executive function in the rhesus monkey (Macaca mulatta). The authors used the category set-shifting task, which requires the monkey to establish a pattern of responding to a specific category (color or shape) based on reward contingency, maintain that pattern of responding, and then shift to responding to a different category when the reward contingency changes. Rhesus monkeys with lesions of the dorsolateral PFC were impaired in abstraction, establishing a response pattern to a specific category and maintaining and shifting that response pattern on the category set-shifting task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory for “what”, “where”, and “when” information in rhesus monkeys (Macaca mulatta).

The present study examined working memory for what, where, and when information in rhesus monkeys (Macaca mulatta) using a computerized task. In Experiment 1, monkeys completed three delayed matching-to-sample (DMTS) tasks: (1) identity DMTS, (2) spatial DMTS, and (3) temporal DMTS. In Experiment 2, the identity and spatial tasks were combined so that monkeys had to report both what and where information about an event. In Experiment 3, the identity, spatial, and temporal tasks were combined to examine what-where-when memory integration. The rhesus monkeys reported all three components of the events, and there was some evidence suggesting that these components were integrated in working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

非人类物种的城市化:动物也是地球上的一员

提出在日益城市化进程中人类与非人类物种之间关系的4种推测。由于非人类物种也在快速城市化,它们的空间条件大部分都是由人类为自己所构建,这可以集中并强化拉图尔的生物共生理念。风景园林师应该理清自己工作的政治影响,而其中的一种方法是处理物种之间微妙而脆弱的相互关系。当然,采用未经验证的新自由主义设计在大多数情况下对非人类物种都会带来特殊的破坏性后果。本文使用"基础设施"模型探讨不同的生物群体之间如何相互影响彼此的命运。     

Developmental and cross-situational stability in infant pigtailed macaque temperament.

We assessed developmental stability and context generalizability of temperament in pigtailed macaques (Macaca nemestrina) from the University of Washington Infant Primate Research Lab. A principal components analysis condensed 6 behavioral measures into 2 components, interpreted as reactivity and boldness. Changes in these measures over the 1st 10 months of development showed a trend toward calmer and bolder behavior with age, with significant individual variation in the pattern of change. Boldness showed a quadratic pattern of change, whereas reactivity decreased linearly. We also studied the relationship between temperament and response to a novelty probe. The magnitude of the response to the novelty probe decreased slightly over time, and boldness and reactivity in a familiar setting did not predict these changes in response to novelty. In a 2nd principal components analysis, reactivity to novelty represented a distinct aspect of temperament. Our results demonstrate developmental changes and context dependency in macaque behavior. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Amygdala size and hypothalamus size predict social play frequency in nonhuman primates: A comparative analysis using independent contrasts.

The amygdala and hypothalamus become sexually differentiated by gonadal hormones giving rise to sexually differentiated behaviors, which include play behavior. Phylogenetic comparative analyses test for relationships between social play and brain structure volumes. Relative volume of the amygdala and hypothalamus correlated with social play, but not nonsocial play, even after controlling for the size of other brain structures. The authors propose that behaviors such as social assessment, recognizing and responding to facial expression, and social response appropriateness, which are mediated by the amygdala, are developed through social play. Additionally, the hypothalamus may regulate the motivation to engage in play through positive reinforcement of pleasurable activity. Thus, the instinctive socioemotive aspects of play in primates appear to be those regulated by the amygdala and hypothalamus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

How much does number matter to a monkey (Macaca mulatta)?

Although many animal species can represent numerical values, little is known about how salient number is relative to other object properties for nonhuman animals. In one hypothesis, researchers propose that animals represent number only as a last resort, when no other properties differentiate stimuli. An alternative hypothesis is that animals automatically, spontaneously, and routinely represent the numerical attributes of their environments. The authors compared the influence of number versus that of shape, color, and surface area on rhesus monkeys' (Macaca mulatta) decisions by testing them on a matching task with more than one correct answer: a numerical match and a nonnumerical (color, surface area, or shape) match. The authors also tested whether previous laboratory experience with numerical discrimination influenced a monkey's propensity to represent number. Contrary to the last-resort hypothesis, all monkeys based their decisions on numerical value when the numerical ratio was favorable. (PsycINFO Database Record (c) 2010 APA, all rights reserved)