The temperature–productivity squeeze: constraints on brook trout growth along an Appalachian river continuum

We tested the hypothesis that brook trout growth rates are controlled by a complex interaction of food availability, water temperature, and competitor density. We quantified trout diet, growth, and consumption in small headwater tributaries characterized as cold with low food and high trout density, larger tributaries characterized as cold with moderate food and moderate trout density, and large main stems characterized as warm with high food and low trout density. Brook trout consumption was highest in the main stem where diets shifted from insects in headwaters to fishes and crayfish in larger streams. Despite high water temperatures, trout growth rates also were consistently highest in the main stem, likely due to competitively dominant trout monopolizing thermal refugia. Temporal changes in trout density had a direct negative effect on brook trout growth rates. Our results suggest that competition for food constrains brook trout growth in small streams, but access to thermal refugia in productive main stem habitats enables dominant trout to supplement growth at a watershed scale. Brook trout conservation in this region should seek to relieve the “temperature–productivity squeeze,” whereby brook trout productivity is constrained by access to habitats that provide both suitable water temperature and sufficient prey.     

A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5–97.5 percentile)] at 15.4 (7.2–31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5–97.5 percentile)] to 13.0 (6.6–25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.     

IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation

The role of inflammation on atherosclerosis and restenosis is well established. Restenosis is thought to be a complex response to injury, which includes early thrombus formation, acute inflammation and neo-intimal growth. Inflammatory cells are likely contributors in the host response to vascular injury, via cytokines and chemokines secretion, including TNF-alpha (TNF). We have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (ECs) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL-10KO) displayed significantly delayed Re-endothelialization and enhanced neo-intimal growth compared to their WT counterparts. Exogenous recombinant IL-10 treatment dramatically blunted the neo-intimal thickening while significantly accelerating the recovery of the injured endothelium in WT mice. In vitro, IL-10 inhibited negative effects of TNF on ECs proliferation, ECs cell cycle, ECs-monocyte adhesion and ECs apoptosis. Furthermore, IL-10 treatment attenuated TNF-induced smooth muscle cells proliferation. Our data suggest that IL-10 differentially regulate endothelial and vascular smooth cells proliferation and function and thus inhibits neo-intimal hyperplasia. Thus, these results may provide insights necessary to develop new therapeutic strategies to limit vascular restenosis during percutaneous coronary intervention (PCI) in the clinics.     

30 Days Wild: Development and Evaluation of a Large-Scale Nature Engagement Campaign to Improve Well-Being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature.     

Effects of febrile temperature on adenoviral infection and replication: implications for viral therapy of cancer

We previously conducted a phase I/II study using arterial infusions of ONYX-015 (dl1520), a replication-selective adenoviral vector, with E1b deleted, for patients with metastatic colorectal cancer. No dose-limiting toxicities occurred, but >90% of the patients experienced fever. The effects of temperature on the replication of dl1520 in normal and transformed cells had not been studied. Therefore, replication and cell viability assays were performed with a panel of nontransformed and transformed cell lines cultured at 37 and 39.5 degrees C and treated with adenovirus type 5 (Ad5) or dl1520. Ad5-mediated cytolytic effects were inhibited and production of infectious particles decreased by >1,000-fold in the nontransformed cells at 39.5 degrees C. Seven of nine of the tumor cell lines retained significant cell-killing effects when treated with Ad5 at 39.5 degrees C. When dl1520 was used, no cytolytic effects were observed at 39.5 degrees C in the nontransformed cell lines; however, cytolytic effects occurred in six of nine tumor cell lines at 39.5 degrees C. Notably, a subset of the tumor cell lines demonstrated increased dl1520-mediated cytolytic effect and replication at 39.5 degrees C. Suppression of Ad5 and dl1520 replication at 39.5 degrees C was not related to p53 status or HSP70 expression. Also, at 39.5 degrees C, E1a expression was inhibited in nontransformed cells but was still abundant in the transformed cells, indicating that a novel early block in viral replication occurred in the nontransformed cells. Fever may therefore augment the therapeutic index of oncolytic viruses by inhibiting replication in normal cells while permitting or enhancing viral replication in some tumor cells.     

Human Enteropathogen Load in Activated Sewage Sludge and Corresponding Sewage Sludge End Products

This study demonstrated a significant reduction in the concentrations of Cryptosporidium parvum and Cryptosporidium hominis oocysts, Giardia lamblia cysts, and spores of human-virulent microsporidia in dewatered and biologically stabilized sewage sludge cake end products compared to those of the respective pathogens in the corresponding samples collected during the sludge activation process.