Influence of hydrological connectivity on winter limnology in 1 floodplain lakes 2 of the Saskatchewan River Delta, SK

Globally, hydrological connectivity between rivers and their floodplains has been reduced by river flow management and land transformation. The Saskatchewan River Delta is North America’s largest inland delta and a hub for fish and fur production. To determine the influence of connectivity on limnology within this northern floodplain, water chemistry and stable isotopes (δ18O and δ236 H) were analyzed during the winter of 2014 in shallow lakes along a hydrological gradient. A total of five lake connectivity categories were determined by optical remote-sensing images of surface water coverage area from years of varying flood intensities. Accuracy of categories were verified by degree of 18O and 239 H enrichment within lakes. Both isotopes showed marked successional enrichment between connectivity categories with more isolated lakes exhibiting greater enrichment. Water chemistry in lakes with greater connectivity to the main channel were characterized by higher pH, dissolved oxygen, nitrates and sulfates, and lower total nitrogen, total phosphorus, and ammonium, compared to more isolated lakes. These findings illustrate how connectivity influences water chemistry in northern floodplain lakes and how it might determine the suitability of these lakes as winter refuge for fishes. Additionally, our study provides supporting evidence for the effective use of optical remote sensing imagery, an inexpensive and accessible source of data for researchers, when determining connectivity characteristics of large northern floodplain systems. Additionally, this study provides further evidence that the inundation of floodplain lakes by river water during peak discharge has an impact on the conditions within the lakes long into the winter ice-cover season. Understanding the year-round influence of river-floodplain connection is imperative for assessing potential impacts of climate change and future water regulation on such ecosystem

Body size is more important than diet in determining stable-isotope estimates of trophic position in crocodilians

The trophic position of a top predator, synonymous with food-chain length, is one of the most fundamental attributes of ecosystems. Stable isotope ratios of nitrogen (δ 15N) have been used to estimate trophic position of organisms due to the predictable enrichment of 15N in consumer tissues relative to their diet. Previous studies in crocodilians have found upward ontogenetic shifts in their 'trophic position'. However, such increases are not expected from what is known about crocodilian diets because ontogenetic shifts in diet relate to taxonomic categories of prey rather than shifts to prey from higher trophic levels. When we analysed dietary information from the literature on the four Amazonian crocodilians, ontogenetic shifts in dietary-based trophic position (TPdiet) were minimal, and differed from those estimated using δ 15N data (TPSIA). Thus, ontogenetic shifts in TPSIA may result not only from dietary assimilation but also from trophic discrimination factors (TDF or Δ 15N) associated with body size. Using a unique TDF value to estimate trophic position of crocodilians of all sizes might obscure conclusions about ontogenetic shifts in trophic position. Our findings may change the way that researchers estimate trophic position of organisms that show orders of magnitude differences in size across their life span. © 2018 The Author(s)

Pollen and spores as biological recorders of past ultraviolet irradiance

Solar ultraviolet (UV) irradiance is a key driver of climatic and biotic change. Ultraviolet irradiance modulates stratospheric warming and ozone production, and influences the biosphere from ecosystem-level processes through to the largest scale patterns of diversification and extinction. Yet our understanding of ultraviolet irradiance is limited because no method has been validated to reconstruct its flux over timescales relevant to climatic or biotic processes. Here, we show that a recently developed proxy for ultraviolet irradiance based on spore and pollen chemistry can be used over long (105 years) timescales. Firstly we demonstrate that spatial variations in spore and pollen chemistry correlate with known latitudinal solar irradiance gradients. Using this relationship we provide a reconstruction of past changes in solar irradiance based on the pollen record from Lake Bosumtwi in Ghana. As anticipated, variations in the chemistry of grass pollen from the Lake Bosumtwi record show a link to multiple orbital precessional cycles (19-21 thousand years). By providing a unique, local proxy for broad spectrum solar irradiance, the chemical analysis of spores and pollen offers unprecedented opportunities to decouple solar variability, climate and vegetation change through geologic time and a new proxy with which to probe the Earth system

One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening

The potential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) escape mutants is a threat to the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutation landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site. We identified escape mutants for five nAbs, including three from the public germline class VH3-53 elicited by natural coronavirus disease 2019 (COVID-19) infection. Escape mutations predominantly mapped to the periphery of the angiotensin-converting enzyme 2 (ACE2) recognition site on the RBD with K417, D420, Y421, F486, and Q493 as notable hotspots. We provide libraries, methods, and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2. &nbsp;</p

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application

Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.We acknowledge funding from the Wellcome Human Cell Atlas Strategic Science Support (WT211276/Z/18/Z); M.H. is funded by Wellcome (WT107931/Z/15/Z), The Lister Institute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre; S.A.T. is funded by Wellcome (WT206194), ERC Consolidator and EU MRG-Grammar awards and; S.B. is funded by Wellcome (WT110104/Z/15/Z) and St. Baldrick’s Foundation; E.L. is funded by a Wellcome Sir Henry Dale and Royal Society Fellowships, European Haematology Association, Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and BBSRC

Energy intake and expenditure assessed ‘in-season’ in an elite European rugby union squad.

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Sport Science on 09/06/2015, available online: http://www.tandfonline.com/doi/pdf/10.1080/17461391.2015.1042528Rugby union (RU) is a complex high-intensity intermittent collision sport with emphasis placed on players possessing high lean body mass and low body fat. After an 8 to 12-week pre-season focused on physiological adaptations, emphasis shifts towards competitive performance. However, there are no objective data on the physiological demands or energy intake (EI) and energy expenditure (EE) for elite players during this period. Accordingly, in-season training load using global positioning system and session rating of perceived exertion (sRPE), alongside six-day assessments of EE and EI were measured in 44 elite RU players. Mean weekly distance covered was 7827 ± 954 m and 9572 ± 1233 m with a total mean weekly sRPE of 1776 ± 355 and 1523 ± 434 AU for forwards and backs, respectively. Mean weekly EI was 16.6 ± 1.5 and 14.2 ± 1.2 megajoules (MJ) and EE was 15.9 ± 0.5 and 14 ± 0.5 MJ. Mean carbohydrate (CHO) intake was 3.5 ± 0.8 and 3.4 ± 0.7 g.kg-1 body mass, protein intake was 2.7 ± 0.3 and 2.7 ± 0.5 g.kg-1 body mass, and fat intake was 1.4 ± 0.2 and 1.4 ± 0.3 g.kg-1 body mass. All players who completed the food diary self-selected a 'low' CHO 'high' protein diet during the early part of the week, with CHO intake increasing in the days leading up to a match, resulting in the mean EI matching EE. Based on EE and training load data, the EI and composition seems appropriate, although further research is required to evaluate if this diet is optimal for match day performance

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years