Canopy Interception of Acid Deposition in Southern Ontario

The impact of tree canopies on acid deposition was examined. Differences in the chemical composition of unintercepted precipitation (dustfall) and canopy was intercepted precipitation (throughfall) at 18 southern Ontario forests, collected during the summers of 1995-1996, were chemically analyzed. The methodology of collection and analysis validated using consistency checks for interception loss, maintenance of electrical neutrality and ion correlation. T-test analyses found throughfall fluxes of K+, Ca2+, Mg2+, and NO3- were significantly higher than dustfall flux (p < 0.05), consistent with other studies. Barrie and nearby sites at Orillia and Bracebridge had larger dustfall depositions of base cations and Cl- suggesting a nearby source of these ions. T-tests revealed large exceedances of pH and sulphate concentration in dustfall over throughfall at the two Scarborough sites; a local point source of sulphates in the Greater Toronto Area was suspected

Angiogenin protects motoneurons against hypoxic injury.

Cells can adapt to hypoxia through the activation of hypoxia-inducible factor-1 (HIF-1), which in turn regulates the expression of hypoxia-responsive genes. Defects in hypoxic signaling have been suggested to underlie the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). We have recently identified mutations in the hypoxia-responsive gene, angiogenin (ANG), in ALS patients, and have shown that ANG is constitutively expressed in motoneurons. Here, we show that HIF-1alpha is sufficient and required to activate ANG in cultured motoneurons exposed to hypoxia, although ANG expression does not change in a transgenic ALS mouse model or in sporadic ALS patients. Administration of recombinant ANG or expression of wild-type ANG protected motoneurons against hypoxic injury, whereas gene silencing of ang1 significantly increased hypoxia-induced cell death. The previously reported ALS-associated ANG mutations (Q12L, K17I, R31K, C39W, K40I, I46V) all showed a reduced neuroprotective activity against hypoxic injury. Our data show that ANG plays an important role in endogenous protective pathways of motoneurons exposed to hypoxia, and suggest that loss of function rather than loss of expression of ANG is associated with ALS

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to searchfor astrophysical neutrino sources. It has so far provided compelling evidencefor a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 observedin coincidence with the high-energy neutrino IceCube-170922A detected byIceCube. The detection of very-high-energy gamma rays (VHE, $\mathrm{E} >100\,\mathrm{GeV}$) from this source helped establish the coincidence andconstrained the modeling of the blazar emission at the time of the IceCubeevent. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) -FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program oftarget-of-opportunity observations of neutrino alerts sent by IceCube. Thisprogram has two main components. One are the observations of known gamma-raysources around which a cluster of candidate neutrino events has been identifiedby IceCube (Gamma-ray Follow-Up, GFU). Second one is the follow-up of singlehigh-energy neutrino candidate events of potential astrophysical origin such asIceCube-170922A. GFU has been recently upgraded by IceCube in collaborationwith the IACT groups. We present here recent results from the IACT follow-upprograms of IceCube neutrino alerts and a description of the upgraded IceCubeGFU system.<br

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Secretome of mesenchymal stem cells and its impact on Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible loss of lung function that stem from two mechanisms, inflammation and senescence. Crosstalk between these two mechanisms accelerate the development of COPD, thus targeting these two pathways may offer benefits in the treatment of COPD. Growing amount of evidence have shown that mesenchymal stem cells as a promising candidate for the treatment of COPD. Over the years, many studies conducted to decipher the therapeutic effect of MSC in COPD and the mechanisms involve, in the hope of utilizing these cells as new therapeutic strategy for COPD. However, the cell-based therapy by using the MSC presented with many obstacles including low engraftment at the site of injury, the risk of microvascular occlusion, unwanted differentiation, and also the risk of malignant transformation. Recently, recently researchers begin to look at the possibility of using MSC derived extracellular vesicles as an alternative to MSC. Here we review the effect of MSC and MSC derived EV in modulating inflammation, and senescence in COPD. We also review current treatment and the side effect in COPD, and senolytic drugs, a new therapeutic strategy targeting the senescent cells

Using a geographic information system to assess local scale methylmercury exposure from fish in nine communities of the Eeyou Istchee territory (James Bay, Quebec, Canada)

Exposure to methylmercury is a concern for those who rely on fish as a traditional food in the Eeyou Istchee territory of James Bay, Quebec, Canada, because industrial land uses overlap with community water bodies where fish are harvested. Consequently, this study assessed if traditional practices, particularly fishing, increased the risk of exposure to methylmercury from the consumption of locally harvested fish. We designed a geographic information system (GIS) that included land use and fish methylmercury tissue concentrations to assess clustering of potential hot spots. We also used generalized linear models to assess the association of fish consumption to blood organic-mercury concentrations, and logistic regression models to assess the probability of fish exceeding the safety threshold for methylmercury tissue concentrations in areas of high intensity land use. The GIS demonstrated significant clustered hot spots around regions of hydroelectric and mining land use. Our results also revealed that adult consumption of pike, lake trout and/or walleye, and child consumption of pike or walleye were significantly associated with blood organic-mercury concentrations. Further, large fish harvested in a community with high intensity land use yielded a 77% probability that the fish exceeded the safety threshold. From a human exposure perspective, our study highlights the need for further research on children who consume fish from this region

Soil Nutrient Supply in Cultivated Bush Bean–Potato Intercropping Grown in Subarctic Soil Managed with Agroforestry

To address food insecurity in northern Canada, some isolated communities started gardening initiatives to reduce dependencies on expensive foods flown in to communities. From 2012–2014, soils in northern Ontario James Bay lowlands were cultivated with bush beans and potatoes, grown in sole and intercropping configurations, in an open field and an agroforestry system enclosed by willow trees. The objective of this study was to compare the supply rates of 15 plant-available nutrients in these soils using in situ ion exchange membranes. After three years of cultivation, the agroforestry site had significantly greater supply of PO4, Ca, and Zn and these nutrients had positive correlations with yield. By contrast, the open site had significantly greater supply of Mg, SO4, and B; these nutrients, and Al, had negative correlations with yield. Whilst there were no differences between sole and intercropping configurations, significantly greater supply of NO3, Ca, Cu, Fe, and Zn occurred early in the growing season, compared to significantly greater supply of K, SO4, B, and Al later in the season. Significantly greater yields have been harvested in the agroforestry site and it is suspected that the presence of a willow shelterbelt improves the microclimate and plant-available PO4, Ca, and Zn

Health and Wellness Impacts of Traditional Physical Activity Experiences on Indigenous Youth: A Systematic Review

Traditional physical activities have numerous physiological and psychosocial benefits for Indigenous youth around the world. Little is known about the positive health and wellness impacts of traditional physical activity experiences on Indigenous youths. The aim of this systematic review is to explore the holistic health and wellness impacts of traditional physical activities on Indigenous youth from certain North American and Oceania geographic areas. A systematic search of four electronic databases (PubMed, ERIC, Scopus and Web of Science) was conducted to identify peer-reviewed publications of qualitative research exploring the diverse health experiences of traditional physical activities for Indigenous youth in Canada, the United States of America, New Zealand and Australia. A qualitative synthesis of studies between 2006 and 2018 were included, and findings were synthesized using an integrated Indigenous-ecological model, which broadly captures health and wellness impacts under intrapersonal, interpersonal, organizational, community and policy level outcomes using medicine wheel teachings. In total, nine studies were identified via this search. Overall, the literature described numerous emotional, mental and spiritual benefits of traditional physical activity, and youth experiences were affected by familial and communal relationships, and systemic factors. Among Indigenous youth, this research shows the importance of including traditional physical activity in future programs and partnerships with community expertise