Identification and characterization of a functional mitochondrial angiotensin system

The renin-angiotensin (Ang) system regulates multiple physiological functions through Ang II type 1 and type 2 receptors. Prior studies suggest an intracellular pool of Ang II that may be released in an autocrine manner upon stretch to activate surface membrane Ang receptors. Alternatively, an intracellular renin-Ang system has been proposed, with a primary focus on nuclear Ang receptors. A mitochondrial Ang system has not been previously described. Here we report that functional Ang II type 2 receptors are present on mitochondrial inner membranes and are colocalized with endogenous Ang. We demonstrate that activation of the mitochondrial Ang system is coupled to mitochondrial nitric oxide production and can modulate respiration. In addition, we present evidence of age-related changes in mitochondrial Ang receptor expression, i.e., increased mitochondrial Ang II type 1 receptor and decreased type 2 receptor density that is reversed by chronic treatment with the Ang II type 1 receptor blocker losartan. The presence of a functional Ang system in human mitochondria provides a foundation for understanding the interaction between mitochondria and chronic disease states and reveals potential therapeutic targets for optimizing mitochondrial function and decreasing chronic disease burden with aging.     

Number without a language model

Cross-cultural studies suggest that access to a conventional language containing words that can be used for counting is essential to develop representations of large exact numbers. However, cultures that lack a conventional counting system typically differ from cultures that have such systems, not only in language but also in many other ways. As a result, it is difficult to isolate the effects of language on the development of number representations. Here we examine the numerical abilities of individuals who lack conventional language for number (deaf individuals who do not have access to a usable model for language, spoken or signed) but who live in a numerate culture (Nicaragua) and thus have access to other aspects of culture that might foster the development of number. These deaf individuals develop their own gestures, called homesigns, to communicate. We show that homesigners use gestures to communicate about number. However, they do not consistently extend the correct number of fingers when communicating about sets greater than three, nor do they always correctly match the number of items in one set to a target set when that target set is greater than three. Thus, even when integrated into a numerate society, individuals who lack input from a conventional language do not spontaneously develop representations of large exact numerosities.     

Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse

HIV-Tat protein has been implicated in the pathogenesis of HIV-1 neurological complications (i.e., neuroAIDS), but direct demonstrations of the effects of Tat on behavior are limited. GT-tg mice with a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein were used to test the hypothesis that the activity of Tat in brain is sufficient to impair learning and memory processes. Western blot analysis of GT-tg mouse brains demonstrated an increase in Tat antibody labeling that seemed to be dependent on the dose and duration of Dox pretreatment. Dox-treated GT-tg mice tested in the Barnes maze demonstrated longer latencies to find an escape hole and displayed deficits in probe trial performance versus uninduced GT-tg littermates, suggesting Tat-induced impairments of spatial learning and memory. Reversal learning was also impaired in Tat-induced mice. Tat-induced mice additionally demonstrated long-lasting (up to one month) deficiencies in novel object recognition learning and memory performance. Furthermore, novel object recognition impairment was dependent on the dose and duration of Dox exposure, suggesting that Tat exposure progressively mediated deficits. These experiments provide evidence that Tat protein expression is sufficient to mediate cognitive abnormalities seen in HIV-infected individuals. Moreover, the genetically engineered GT-tg mouse may be useful for improving our understanding of the neurological underpinnings of neuroAIDS-related behaviors.     

The association between serious psychological distress and emergency department utilization among young adults in the USA

Purpose

Psychological problems could lead to several adverse health outcomes and were strongly correlated with cigarette smoking and alcohol consumption. In addition, patients treated in EDs were vulnerable to psychological problems. We therefore examined the population-level association between serious psychological distress (SPD) and emergency department (ED) use among young adults in the USA. We also studied the additive effects of SPD, cigarette smoking, and alcohol consumption on the ED presentation.

Methods

The study sample contains 16,873 individuals, using data from the National Health Interview Survey, from 2004 to 2006. Bivariate analyses with chi-square tests and logistic regression analyses are performed.

Results

Young adults having SPD were 2.05 times more likely to go to an ED. People having SPD and being a current smoker were 2.52 times more likely to use services in an ED. However, people having SPD and being a heavy drinker did not have a significantly elevated risk of ED use.

Conclusion

An association between SPD and ED use among US young adults is established in this study. Attempts to decrease excess ED use and the development of strategies to improve mental health among young adults are needed to improve patient health and reduce the health-care burden of high costs and deteriorating ED care quality.     

Evolving role of FDG PET imaging in assessing joint disorders: a systematic review

Assessing joint disorders has been a relatively recent and evolving application of ¹⁸F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) imaging. FDG is taken up by inflammatory cells, particularly when they are active as part of an ongoing inflammatory process. Hence FDG PET has been employed to assess a wide array of arthritic disorders. FDG PET imaging has been investigated in various joint diseases for diagnostic purposes, treatment monitoring, and as a prognostic indicator as in other disorders. In some of the diseases the ancillary findings in FDG PET have provided important clues about the underlying pathophysiology and pathogenesis processes. While substantial promise has been demonstrated in a number of studies, it is clear that the potential utility of PET in this clinical realm far outweighs that which has been established to date.