Measurement of respiratory function in isolated cardiac mitochondria using Seahorse XFe24 Analyzer: applications for aging research

Mitochondria play a critical role in the cardiomyocyte physiology by generating majority of the ATP required for the contraction/relaxation through oxidative phosphorylation (OXPHOS). Aging is a major risk factor for cardiovascular diseases (CVD) and mitochondrial dysfunction has been proposed as potential cause of aging. Recent technological innovations in Seahorse XFe24 Analyzer enhanced the detection sensitivity of oxygen consumption rate and proton flux to advance our ability study mitochondrial function. Studies of the respiratory function tests in the isolated mitochondria have the advantages to detect specific defects in the mitochondrial protein function and evaluate the direct mitochondrial effects of therapeutic/pharmacological agents. Here, we provide the protocols for studying the respiratory function of isolated murine cardiac mitochondria by measuring oxygen consumption rate using Seahorse XFe24 Analyzer. In addition, we provide details about experimental design, measurement of various respiratory parameters along with interpretation and analysis of data.     

Screening for neurocognitive impairment in HIV-positive adults aged 50 years and older: Montreal Cognitive Assessment relates to self-reported and clinician-rated everyday functioning

As the HIV+ population ages, the risk for and need to screen for HIV-associated neurocognitive disorders (HAND) increases. The aim of this study is to determine the utility and ecological validity of the Montreal Cognitive Assessment (MoCA) among older HIV+ adults. A total of 100 HIV+ older adults aged 50 years or over completed a comprehensive neuromedical and neurocognitive battery, including the MoCA and several everyday functioning measures. The receiver operating characteristic curve indicates ≤26 as the optimal cut-off balancing sensitivity (84.2%) and specificity (55.8%) compared to “gold standard” impairment as measured on a comprehensive neuropsychological battery. Higher MoCA total scores are significantly (p < .01) associated with better performance in all individual cognitive domains except motor abilities, with the strongest association with executive functions (r = ?0.49, p < .01). Higher MoCA total scores are also significantly (p <.01) associated with fewer instrumental activities of daily living declines (r = ?0.28), fewer everyday cognitive symptoms (r = ?0.25), and better clinician-rated functional status (i.e., Karnofsky scores; r = 0.28); these associations remain when controlling for depressive symptoms. HIV+ individuals who are neurocognitively normal demonstrate medium-to-large effect size differences in their MoCA performance compared to those with asymptomatic neurocognitive impairment (d = 0.85) or syndromic HAND (mild neurocognitive disorder or HIV-associated dementia; d = 0.78), while the latter two categories do not differ. Although limited by less than optimal specificity, the MoCA demonstrates good sensitivity and ecological validity, which lends support to its psychometric integrity as a brief cognitive screening tool among older HIV+ adults.     

Triggering receptor expressed on myeloid cells and 5’adenosine monophosphate-activated protein kinase in the inflammatory response: a potential therapeutic target

Introduction: The events in the cellular and molecular signaling triggered during inflammation mitigate tissue healing. The metabolic check-point control mediated by 5?-adenosine monophosphate-activated protein kinase (AMPK) is crucial for switching the cells into an activated state capable of mediating inflammatory events. The cell metabolism involved in the inflammatory response represents a potential therapeutic target for the pharmacologic management of inflammation.

Areas covered: In this article, a critical review is presented on triggering receptor expressed on myeloid cell (TREM) receptors and their role in the inflammatory responses, as well as homeostasis between different TREM molecules and their regulation. Additionally, we discussed the relationship between TREM and AMPK to identify novel targets to limit the inflammatory response. Literature search was carried out from the National Library of Medicine’s Medline database (using PubMed as the search engine) and Google Scholar and identified relevant studies up to 30 March 2016 using inflammation, TREM, AMPK, as the key words.

Expert commentary: The prevention of phenotype switching of immune cells during inflammation by targeting AMPK and TREM-1 could be beneficial for developing novel management strategies for inflammation and associated complications.     

The imprint of China’s first emperor on the distant realm of eastern Shandong

Imperial expansion is recurrent in human history. For early empires, such as in ancient China, this process generally is known from texts that glorify and present the perspective of victors. The legacy of the Qin king, Shihuangdi, who first unified China in 221 BC, remains vital, but we have few details about the consequences of his distant conquests or how they changed the path of local histories. We integrate documentary accounts with the findings of a systematic regional survey of archaeological sites to provide a holistic context for this imperialistic episode and the changes that followed in coastal Shandong.