High-fat diet-induced resistance to helminth infection via alternative induction of type 2 immunity

Gastrointestinal nematode infections cause morbidity and socioeconomic loss in the most deprived communities. The shift in the context of obesity has led to spatial overlap with endemic gastrointestinal nematode regions resulting in the emergence of a novel comorbidity. Despite this, the impact of a high-fat diet (HFD) on immune-regulated protection against gastrointestinal infections remains largely unknown. We employed the murine model of nematode infection, Trichuris muris, to investigate the effect of an HFD on the immune response against chronic infection. Surprisingly, diet-induced obesity drove parasite expulsion in both single and repeated trickle low doses of T. muris eggs. Mechanistically, an HFD increased the expression of the ST2 receptor on CD4+ T cells, priming an enhanced type 2 helper T (Th2) cell cytokine production following interleukin (IL)-33 stimulation ex vivo. Despite IL-33−/− mice demonstrating that IL-33 is not critical for host protective immunity to T. muris under a conventional diet, HFD-fed T-cell deplete mice adoptively transferred with ST2−/− CD4 T cells were unable to expel a T. muris infection unlike those transferred with ST2-sufficient cells. Collectively, this study demonstrates that an HFD primes CD4+ T cells to utilize the IL-33-ST2 axis in a novel induction of type 2 immunity, providing insights into the emerging comorbidities of obesity and nematode infection

Psychosocial correlates with depressive symptoms six years after a first episode of psychosis as compared with findings from a general population sample

BACKGROUND: Depression is frequently occurring during and after psychosis. The aim of this study was to analyze if the psychosocial characteristics associated with depression/depressive symptoms in the late phase of a first episode psychosis (FEP) population were different compared to persons from the general population. METHODS: A questionnaire was sent out to all individuals six years after their FEP and to a general population sample. Depressive symptoms were recorded using a self-rating scale, the Major Depression Inventory. RESULTS: Formerly FEP persons had a higher representation of depressive symptoms/depression, unemployment, financial problems and insufficient social network. Depressive symptoms/depression were found to be associated with psychosocial problems. An age and gender effect was found in the general population, but not in the FEP sample. When the psychosocial characteristics were taken into account there were no association between having had FEP and depressive symptoms. CONCLUSIONS: The association between having been a FEP patient and depressive symptoms/depression disappeared when negative social aspects were taken into account

Assessing trends and predictors of tuberculosis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Variety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines.</p> <p>Methods</p> <p>The generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales.</p> <p>Results</p> <p>We found that (<it>i</it>) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person^-1yr^-1, (<it>ii</it>) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (<it>iii</it>) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (<it>iv</it>) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations.</p> <p>Conclusions</p> <p>The proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.</p

Spatial extent and historical context of North Sea oxygen depletion in August 2010

Prompted by recent observations of seasonal low dissolved oxygen from two moorings in the North Sea, a hydrographic survey in August 2010 mapped the spatial extent of summer oxygen depletion. Typical near-bed dissolved oxygen saturations in the stratified regions of the North Sea were 75–80 % while the well-mixed regions of the southern North Sea reached 90 %. Two regions of strong thermal stratification, the area between the Dooley and Central North Sea Currents and the area known as the Oyster Grounds, had oxygen saturations as low as 65 and 70 % (200 and 180 µmol dm-3) respectively. Low dissolved oxygen was apparent in regions characterised by low advection, high stratification, elevated organic matter production from the spring bloom and a deep chlorophyll maximum. Historical data over the last century from the International Council for the Exploration of the Sea oceanographic database highlight an increase in seasonal oxygen depletion and a warming over the past 20 years. The 2010 survey is consistent with, and reinforces, the signal of recent depleted oxygen at key locations seen in the (albeit sparse) historical data

Endothelin-1 enhances fibrogenic gene expression, but does not promote DNA synthesis or apoptosis in hepatic stellate cells

BACKGROUND: In liver injury, the pool of hepatic stellate cell (HSC) increases and produces extracellular matrix proteins, decreasing during the resolution of fibrosis. The profibrogenic role of endothelin-1 (ET-1) in liver fibrosis remains disputed. We therefore studied the effect of ET-1 on proliferation, apoptosis and profibrogenic gene expression of HSCs. RESULTS: First passage HSC predominantly expressed endothelin A receptor (ETAR) mRNA and 4th passage HSC predominantly expressed the endothelin B receptor (ETBR) mRNA. ET-1 had no effect on DNA synthesis in 1st passage HSC, but reduced DNA synthesis in 4th passage HSC by more than 50%. Inhibition of proliferation by endothelin-1 was abrogated by ETBR specific antagonist BQ788, indicating a prominent role of ETBR in growth inhibition. ET-1 did not prevent apoptosis induced by serum deprivation or Fas ligand in 1st or 4th passage HSC. However, ET-1 increased procollagen α1(I), transforming growth factor β-1 and matrix metalloproteinase (MMP)-2 mRNA transcripts in a concentration-dependent manner in 1st, but not in 4th passage HSC. Profibrogenic gene expression was abrogated by ETAR antagonist BQ123. Both BQ123 and BQ788 attenuated the increase of MMP-2 expression by ET-1. CONCLUSION: We show that ET-1 stimulates fibrogenic gene expression for 1st passage HSC and it inhibits HSC proliferation for 4th passage HSC. These data indicate the profibrogenic and antifibrogenic action of ET-1 for HSC are involved in the process of liver fibrosis

The intraductal approach to the breast: raison d'être

Opportunities for the detection, prediction, and treatment of breast cancer exist at three biological levels: systemically via the blood, at the whole organ level, and within the individual ductal lobular structures of the breast. This review covers the evaluation of approaches targeted to the ductal lobular units, where breast cancer begins. Studies to date suggest the presence of 5 to 12 independent ductal lobular systems per breast, each harboring complex cellular fluids contributed by local and systemic processes. New techniques for accessing and interrogating these systems offer the potential to gauge the microenvironment of the breast and distill biological risk profiles

Inferring transient dynamics of human populations from matrix non-normality

This is the final version of the article. Available from Springer Verlag via the DOI in this record.In our increasingly unstable and unpredictable world, population dynamics rarely settle uniformly to long-term behaviour. However, projecting period-by-period through the preceding fluctuations is more data-intensive and analytically involved than evaluating at equilibrium. To efficiently model populations and best inform policy, we require pragmatic suggestions as to when it is necessary to incorporate short-term transient dynamics and their effect on eventual projected population size. To estimate this need for matrix population modelling, we adopt a linear algebraic quantity known as non-normality. Matrix non-normality is distinct from normality in the Gaussian sense, and indicates the amplificatory potential of the population projection matrix given a particular population vector. In this paper, we compare and contrast three well-regarded metrics of non-normality, which were calculated for over 1000 age-structured human population projection matrices from 42 European countries in the period 1960 to 2014. Non-normality increased over time, mirroring the indices of transient dynamics that peaked around the millennium. By standardising the matrices to focus on transient dynamics and not changes in the asymptotic growth rate, we show that the damping ratio is an uninformative predictor of whether a population is prone to transient booms or busts in its size. These analyses suggest that population ecology approaches to inferring transient dynamics have too often relied on suboptimal analytical tools focussed on an initial population vector rather than the capacity of the life cycle to amplify or dampen transient fluctuations. Finally, we introduce the engineering technique of pseudospectra analysis to population ecology, which, like matrix non-normality, provides a more complete description of the transient fluctuations than the damping ratio. Pseudospectra analysis could further support non-normality assessment to enable a greater understanding of when we might expect transient phases to impact eventual population dynamics.This work was funded by Wellcome Trust New Investigator 103780 to TE, who is also funded by NERC Fellowship NE/J018163/1. JB gratefully acknowledges the ESRC Centre for Population Change ES/K007394/1

Public Attitudes Towards Moral Enhancement. Evidence that Means Matter Morally

To gain insight into the reasons that the public may have for endorsing or eschewing pharmacological moral enhancement for themselves or for others, we used empirical tools to explore public attitudes towards these issues. Participants (N = 293) from the United States were recruited via Amazon’s Mechanical Turk and were randomly assigned to read one of several contrastive vignettes in which a 13-year-old child is described as bullying another student in school and then is offered an empathy-enhancing program. The empathy-enhancing program is described as either involving taking a pill or playing a video game on a daily basis for four weeks. In addition, participants were asked to imagine either their own child bullying another student at school, or their own child being bullied by another student. This resulted in a 2 × 2 between-subjects design. In an escalating series of morally challenging questions, we asked participants to rate their overall support for the program; whether they would support requiring participation; whether they would support requiring participation of children who are at higher risk to become bullies in the future; whether they would support requiring participation of all children or even the entire population; and whether they would be willing to participate in the program themselves. We found that people were significantly more troubled by pharmacological as opposed to non-pharmacological moral enhancement interventions. The results indicate that members of the public for the greater part oppose pharmacological moral bioenhancement, yet are open to non-biomedical means to attain moral enhancement. [248 words]