Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice

Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.     

Enhanced cognitive activity--over and above social or physical activity--is required to protect Alzheimer's mice against cognitive impairment, reduce Abeta deposition, and increase synaptic immunoreactivity

Although social, physical, and cognitive activities have each been suggested to reduce the risk of Alzheimer's disease (AD), epidemiologic studies cannot determine which activity or combination of activities is most important. To address this question, mutant APP transgenic AD mice were reared long-term in one of four housing conditions (impoverished, social, social+physical, or complete enrichment) from 1(1/2) through 9 months of age. Thus, a stepwise layering of social, physical, and enhanced cognitive activity was created. Behavioral evaluation in a full battery of sensorimotor, anxiety, and cognitive tasks was carried out during the final 5 weeks of housing. Only AD mice raised in complete enrichment (i.e., enhanced cognitive activity) showed: (1) protection against cognitive impairment, (2) decreased brain beta-amyloid deposition, and (3) increased hippocampal synaptic immunoreactivity. The protection provided by enhanced cognitive activity spanned multiple cognitive domains (working memory, reference learning, and recognition/identification). Cognitive and neurohistologic benefits of complete enrichment occurred without any changes in blood cytokine or corticosterone levels, suggesting that enrichment-dependent mechanisms do not involve changes in the inflammatory response or stress levels, respectively. These results indicate that the enhanced cognitive activity of complete enrichment is required for cognitive and neurologic benefit to AD mice-physical and/or social activity are insufficient. Thus, our data suggest that humans who emphasize a high lifelong level of cognitive activity (over and above social and physical activities) will attain the maximal environmental protection against AD.     

Housing First and Photovoice: Transforming Lives,Communities, and Systems

This article presents findings from a community‐based participatory evaluation of a Housing First program on the Island of O'ahu. In this study, clients in a Housing First program used Photovoice to evaluate the program and to advocate for progressive housing policies. Written together by members of the Housing First Photovoice group, this collaborative article describes the outcomes from both the Housing First program and the Photovoice project and demonstrates the ways in which participatory program evaluations can interact with client‐driven programs like Housing First to produce a cumulative, transformative impact. Findings suggest that community psychologists hoping to re‐engage with community mental health systems through enacting transformative change should consider taking a community‐based participatory approach to program evaluation because increased client voice in community mental health programs and their evaluations can have far‐reaching, transformative impacts for research, practice, and policy.     

Spontaneous atom mixing and unmixing in metallic nanoparticles

The behaviour of atom mixing and unmixing in metallic nanoparticles has been studied in situ by transmission electron microscopy, using particles in the Au₂Pb-Sn system. It is confirmed that not only spontaneous mixing but also spontaneous unmixing take place in Au₂Pb particles. At room temperature, spontaneous mixing of tin atoms into Au₂Pb particles takes place, and this mixing induces unmixing of lead from Au₂Pb, resulting in the formation of AuSn particles accompanied by lead precipitates.     

Direct evidence that an apparent splitting pattern of gamma particles in Ni alloys is a stage of coalescence

High-resolution electron microscopy is used to determine the translation order domains of gamma particles in arrangements formed during Ostwald ripening in the alloy Ni-12at.%Al. Such arrangements have been often identified with the operation of a mechanism of particle splitting in the late stages of the coarsening process, that is when the elastic strain contribution becomes predominant. It is shown that the translation order domains are not identical in such a particle array. This leads to the conclusion that particle splitting is not necessarily the mechanism responsible for the formation of such characteristic particle arrangements. Instead, particle migration can also be considered to be the responsible mechanism for the formation of such a correlated gamma-particle spatial distribution observed in Ni-based alloys.     

Modulation of motor area activity during observation of unnatural body movements

The mirror neuron system (MNS) is activated when observing the actions of others. However, it remains unclear whether the MNS responds more strongly to natural bodily actions in the observer’s motor repertoire than to unnatural actions. We investigated whether MNS activity is modulated by the unnaturalness of an observed action by inserting short pauses in the middle of the action (0, 2, and 6 pauses; no-pause, pause-1, and pause-2 conditions, respectively). The results indicated that the number of pauses significantly affected motor area activity. Subsequent analyses revealed significant differences between the pause-1 and pause-2 conditions (P < 0.01), as well as the no-pause and pause-2 conditions (P < 0.05). There was significant activation in the pause-1 condition (P < 0.001), while significant deactivation was observed in the pause-2 condition (P < 0.05). These results indicate that MNS activity is modulated by the kinematic characteristics of the observed action. We suggest the possibility that a slightly deviated action may enhance the MNS activity during action observation, while a highly unnatural action would lead to a strong attenuation (deactivation) of activity in the MNS.     

Spatial attention and reaction times during smooth pursuit eye movement

To examine the spatial shift of attention during smooth pursuit, we measured reaction times (RTs) to a visual target that appeared during pursuit. Participants pursued a moving row of circular frames and responded to a target presented within one of the frames. The results showed large RT differences between stimulus velocities up to 5o/s and 10o/s or above. RTs were faster for a target appearing in the pursuit direction than for one in the opposite direction. When an auditory precue was presented, the RTs during pursuit at 10o/s were faster with increases in the stimulus onset asynchrony (SOA) between the cue and the target. Furthermore, RTs were faster in the cued than in the uncued direction. These results not only support the idea that RTs during pursuit reflect the operation of attention, but also suggest that attention during pursuit can be shifted by the abrupt onset of a target stimulus and/or by prior information regarding the onset of a target stimulus.     

Reading performance in middle-aged adults with declines in accommodation

The present study investigated the effects of presbyopia on the reading ability of middle-aged adults in a Japanese reading context, using the rapid serial visual presentation paradigm. Japanese words, each consisting of three characters, were sequentially presented at the same location on a display screen. Participants were instructed to read the words aloud as accurately as possible, irrespective of their order within the sequence. Experiment 1 showed that the reading performance for the presbyopes was far worse for the near-viewing (35?cm) than for the far-viewing (70?cm) conditions when the words were presented at 0.4° in character size. Experiment 2 investigated in detail the effect of luminance contrast on reading at a viewing distance of 35?cm. The minimums of the exposure durations within which the participants could read the words above 89.9?% correct (minimum exposure duration) were 498?ms/word for the presbyopes and 134?ms/word for the nonpresbyopes, both of which values were obtained at 100?% contrast. The critical contrast??that is, the contrast that doubled the minimum exposure duration that had been obtained at 100?% contrast??was considerably higher for the presbyopes (39.2?%) than for the nonpresbyopes (16.4?%). However, the reading performance for the presbyopes was improved more than threefold when the contrast was increased to 100?% in both experiments. Thus, our results provide psychophysical evidence for the dependency of presbyopes?? reading on viewing distance and luminance contrast.