Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging

Microglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ42) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ42 markedly induced BV2 cell ROS production, Nox2 expression, p47phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20– 22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ42 stimulation and in aging-associated microgliosis and brain inflammation

Validity of a food-frequency questionnaire for elderly men in southeast China

OBJECTIVE: To investigate the internal validity of a food-frequency questionnaire (FFQ) developed for a case-control study of prostate cancer in southeast China. DESIGN: A comprehensive questionnaire comprising a quantitative FFQ and a short food habit questionnaire (SFHQ) was developed and modified from previous cancer and nutritional studies. The Goldberg formula (ratio of energy intake (EI) to basal metabolic rate (BMR), EI/BMR) was used to assess the validity of the FFQ by making comparisons with physical activity levels. Physical activity levels were measured by the estimated total metabolic equivalents (MET) and the ratio of energy expenditure (EE) to BMR (EE/BMR). Correlation analyses were undertaken to compare the SFHQ variables with those of the quantitative FFQ. SETTING: Hangzhou, Zhejiang Province, China. SUBJECTS: A total of 404 men over 45 years old with or without prostate cancer were recruited from eight hospitals.RESULTS: The partial correlation coefficients, controlling for age and family history of prostate cancer, were moderate to high (P<0.05) for preserved foods intake, fat consumption and tea drinking variables between the SFHQ and the quantitative FFQ. The average EI/BMR was 1.72, with 76% of subjects exceeding the Goldberg cut-off value of 1.35. Apart from weight, BMI, EE/BMR and MET, there were no significant differences in characteristics between low (<1.35) and normal EI/BMR groups. CONCLUSIONS: The FFQ is demonstrated to be a valid instrument to measure energy and food intake for elderly men in southeast China

Tea and lycopene protect against prostate cancer

Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men.Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake

Does the Consumption of Green Tea Reduce the Risk of Lung Cancer Among Smokers?

Experimental and epidemiological studies were reviewed to assess whether the consumption of green tea could reduce the risk of lung cancer in smokers. Articles published since 1990 were located by searching electronic databases PubMed, Ovid and Science Direct, using keywords ‘lung cancer’, ‘tea’ and ‘smoking’ without any restriction on language. After relevant articles had been located, further papers were obtained from their reference lists. Evidence from experimental studies (in vitro animal and human trials) suggested that regular intake of green tea may be protective against tobacco carcinogens. However, the mechanism behind the protective effect is only partly understood. In most of the epidemiological studies reviewed, the green tea exposure was within 5 years of the interview or follow-up, which would coincide with the induction period and latent period of lung cancer. Longer term studies are thus needed to further quantify the cancer risk. There is some evidence suggesting regular intake of green tea at high level (>3 cups per day) may reduce the risk of smokers developing lung cancer. Improvement in measuring green tea intake is required in order to confirm the evidence from epidemiological studies

Deciphering the general factor in interest measures: response style or attitude

Unrotated factor analyses of interest data have consistently yielded a general factor of interests, an overarching factor with uniformly high loadings across interest subscales and individual items. The theoretical significance of this general factor of interest is still debated. In this paper, we aim to discriminate between two dominant interpretations of the general factor of interest—as either a substantive factor with meaning in the field of personality and interest, or as a measurement artifact which should be disregarded. Across four independent samples, we evaluate these competing interpretations of the general factor. We compare the general factor with broad personality measures that represent a general propensity for ‘liking’ stimuli, as well as an index of acquiescent response styles. More specifically, we test the general factor against measures of dispositional attitudes, neutral objects satisfaction, and acquiescent responding. Our results support the idea that the general factor of interests can be explained more from the standpoint of a general dispositional attitude to respond favorably towards objects and activities, rather than an acquiescence response style or neutral objects satisfaction. The general factor of interests can thus be used to offer insight into an individuals’ personality and is worth reporting in interest assessment results

Resolving the order parameter of High-Tc_{c} Superconductors through quantum pumping spectroscopy

The order parameter of High-T$_{c}$ superconductors through a series of experiments has been quite conclusively demonstrated to not be of the normal $s-wave$ type. It is either a pure $d_{x^{2}-y^{2}}$-wave type or a mixture of a $d_{x^{2}-y^{2}}-wave$ with a small imaginary $s-wave$ or $d_{xy}-wave$ component. In this work a distinction is brought out among the four types, i.e., $s- wave$, $d_{x^{2}-y^{2}}- wave$, $d_{x^{2}-y^{2}}+is - wave$ and $d_{x^{2}-y^{2}}+id_{xy}- wave$ types with the help of quantum pumping spectroscopy. This involves a normal metal double barrier structure in contact with a High-T$_{c}$ superconductor. The pumped current, heat and noise show different characteristics with change in order parameter revealing quite easily the differences among these.Comment: 11 pages, 3 figures, 1 table, Manuscript revised with new material on d+id' cas

Organizational Resources, Country Institutions, and National Culture behind Firm Survival and Growth during COVID-19

This paper provides one of the first comprehensive and most updated studies on the effects of firms’ organizational resources, country institutions, and national culture on the survival and growth of private firms around the world during the COVID-19 pandemic. Analyzing World Bank Enterprise Follow-up Surveys on COVID-19 that cover 18,770 firms in 36 countries, the paper documents four sets of findings. (1) During the pandemic, firms with favorable organizational resources (state ownership and affiliation with parent companies) are more likely to survive and grow, whereas firms with foreign ownership or more financial obstacles are less likely to survive or grow. Firms in countries with a higher per capita income, a lower COVID-19 spread, and a less stringent COVID-19 control policy are more likely to survive and grow. (2) Favorable ownership and parent-company affiliations help cushion the pandemic shock during the pandemic. (3) The relationship between firm characteristics and firm survival/growth is significantly affected by the stringency of a country’s COVID-19 policy. (4) Firm survival and growth are positively related to a country’s cultural tendency in terms of long-term orientation and are not significantly related to uncertainty avoidance and individualism. The overall quality of country governance is negatively linked to the odds for firm survival as well as revenue and employment growth

A two-part mixed-effects model for analyzing clustered time-to-event data with clumping at zero

In longitudinal epidemiological studies consisting of a baseline stage and a follow-up stage, observations at the baseline stage may contain a countable proportion of negative responses. The time-to-event outcomes of those observations corresponding to negative responses at baseline can be denoted as zeros, which are excluded from standard survival analysis. Consequently, some important information on these subjects is therefore lost in the analysis. Furthermore, subjects are often clustered within hospitals, communities or health service centers, resulting in correlated observations. The framework of the two-part model has been developed and utilized widely to analyze semi-continuous data or count data with excess zeros, but its application to clustered time-to-event data with clumping at zero remains sparse.This study was partially supported by China Scholarship Council (Grant NO: 201406240008)

Laboratory-directed evolution as a tool for anticipating insecticide resistance

The evolution of insecticide resistance provides a eukaryotic model system for studying enzyme evolution. Understanding the molecular basis of insecticide resistance can assist both the development of new methods to combat resistance and the anticipation of future resistance. Three insect species have independently evolved catalytic organophosphate (OP) insecticide resistance through a single active-site mutation (Gly\u3eAsp) in the αE7 enzyme1-3. To explore the evolutionary potential of αE7, we subjected αE7 from the blowfly Lucilia cuprina to nine rounds of mutation and selection, resulting in a \u3e1000-fold increase in OP-hydrolase activity and a kcat / KM \u3e 106 M-1 min-1. Kinetic and structural analysis of the evolutionary trajectory revealed the molecular basis for the increase in catalytic efficiency. Mutations occurring in the early stages of the trajectory enrich the productive side chain conformation of the key aspartic acid residue, while mutations in later stages remodel the binding pocket. Remarkably, mutations appearing in the later rounds yielded larger improvements in catalytic efficiency compared to initial mutations, indicating that the initial Gly\u3eAsp mutation represents only a fraction of the αE7 evolutionary potential. Worryingly, this suggests that the Gly\u3eAsp could be the first of many steps toward efficient OP-insecticide detoxification. Please click Additional Files below to see the full abstract