A Procedure for Determining the Relative Volume of Mitochondria in Hepatic Cells

About forty years ago Cowdry\u27s monograph on mitochondria appeared evaluating the work of previous investigators, indicating synonymy and, in a sense, bringing the first exploratory phase of the study of these cellular constituents to a close (1). Reasonably specific methods for their demonstration had been devised, and it was possible to have some confidence in the conclusions that the so-called mitochondria of different kinds of cells, despite dissimilarities in size or shape, were comparable cellular parts

U5a1 Mitochondrial DNA Haplotype Identified in Eneolithic Skeleton from Shatar Chuluu, Mongolia

The mitochondrial haplotype U5a1 was identified from an Eneolithic grave associated with the Afanasievo archaeological culture in Bayankhongor Province, Erdenetsogt Township, at the site of Shatar Chuluu. This is the earliest appearance of a mtDNA haplotype associated with modern European populations on the Mongol Steppe. This evidence demonstrations that people with “western” mtDNA lived on the Mongol Steppe east of the Altai Mountains before the Bronze Age and refutes the notion that the Altai Mountains were a substantial barrier to gene flow and definitively expands the acknowledged range of the Afanasievo archaeological culture

Immigration and the Common Profit: Native Cloth Workers, Flemish Exiles, and Royal Policy in Fourteenth-Century London

Drawing on a wide variety of published and unpublished sources, this article reconstructs a crucial episode in the relationship between the English Crown, its native subjects and the kingdom’s immigrant population during the later Middle Ages. Determined that their presence would boost the development of the local textile industries, Edward III encouraged high numbers of skilled Flemish cloth workers who had been exiled from their home county at the start of the 1350s to settle in the realm. Most of them took up residence in London, where they produced higher-quality cloth for the domestic market and, probably, for export. Soon, however, the immigrants’ activities conflicted with the privileges that had structured the capital’s economic life for centuries. Their work was contested by London’s native weavers who, since the middle of the twelfth century, had enjoyed the sole right to produce cloth in the city. Hoping that the control over the immigrants’ activities would help them to overcome the crisis in the market for lower-quality textiles they were struggling with, the natives petitioned the king to obtain the incorporation of the Flemish weavers into their guild for over twenty-five years. Yet, arguing that the Flemings’ contribution benefited the common profit of the whole kingdom in a way that transcended the interests of any particular group, the Crown rejected all their requests and avoided every attempt at discussion. Each time political communication broke down, the native weavers took out their frustrations by physically attacking their Flemish counterparts. These incidents became increasingly violent during the years leading up to the Peasants’ Revolt in 1381 and came to a dramatic conclusion during the rebellion itself

Mindfulness Training for Improving Attention Regulation in University Students: Is It Effective? and Do Yoga and Homework Matter?

The present study examined the effects of mindfulness training on attention regulation in university students and whether the potential benefits of implementation are influenced by the yoga component of mindfulness-based interventions (MBIs) and/or by MBI homework practice. In a non-randomized trial with pre- and post-assessments, n = 180 university students were allocated to either mindfulness training (experimental groups), awareness activities (active control group), or no training (passive control group). Mindfulness was taught through two MBIs, one including yoga and the other excluding yoga. Attention regulation was operationalized via behavioral indicators, namely sustained attention, cognitive flexibility, cognitive inhibition, and data-driven information processing. With the exception of speed in a cognitive flexibility task, the results indicated no systematic or differential advantage arising from mindfulness training, with or without yoga, regarding the aspects of attention regulation. There was no consistent influence of homework quantity or quality. The implications for mindfulness training in academic contexts are discussed

Decision making as a predictor of first ecstasy use: a prospective study

Ecstasy (+/- 3,4-methylenedioxymethamphetamine) is a widely used recreational drug that may damage the serotonin system and may entail neuropsychological dysfunctions. Few studies investigated predictors for ecstasy use. Self-reported impulsivity does not predict the initiation of ecstasy use; the question is if neuropsychological indicators of impulsivity can predict first ecstasy use. This study tested the hypothesis that a neuropsychological indicator of impulsivity predicts initiation of ecstasy use. Decision-making strategy and decision-making reaction times were examined with the Iowa Gambling Task in 149 ecstasy-naive subjects. The performance of 59 subjects who initiated ecstasy use during a mean follow-up period of 18 months (range, 11-26) was compared with the performance of 90 subjects that remained ecstasy-naive. Significant differences in decision-making strategy between female future ecstasy users and female persistent ecstasy-naive subjects were found. In addition, the gap between decision-making reaction time after advantageous choices and reaction time after disadvantageous choices was smaller in future ecstasy users than in persistent ecstasy-naives. Decision-making strategy on a gambling task was predictive for future use of ecstasy in female subjects. Differences in decision-making time between future ecstasy users and persistent ecstasy-naives may point to lower punishment sensitivity or higher impulsivity in future ecstasy users. Because differences were small, the clinical relevance is questionabl

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival