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257 result(s) for "Thomson, Russell"
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Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: Relevance to trypanosome lysis
Significance African trypanosomes are parasites that can cause African sleeping sickness in humans. Host defense against some of these is provided by the human serum factor apolipoprotein L-1 (APOL1), which causes swelling and lysis of susceptible trypanosomes. Lysis follows uptake of APOL1 into acidic parasite endosomes and is thought to involve ion influx across the plasma membrane. In this paper we show that, after interaction of APOL1 with lipid bilayers at acidic pH, subsequent pH neutralization triggers the opening of pH-gated channels that selectively conduct cations across the bilayer. Based on these results, we propose a mechanism of trypanosome lysis that involves endocytic recycling of APOL1 and the opening of APOL1-induced cation-selective channels, at neutral pH, in the parasite plasma membrane. Apolipoprotein L-1 (APOL1), the trypanolytic factor of human serum, can lyse several African trypanosome species including Trypanosoma brucei brucei , but not the human-infective pathogens T. brucei rhodesiense and T. brucei gambiense , which are resistant to lysis by human serum. Lysis follows the uptake of APOL1 into acidic endosomes and is apparently caused by colloid-osmotic swelling due to an increased ion permeability of the plasma membrane. Here we demonstrate that nanogram quantities of full-length recombinant APOL1 induce ideally cation-selective macroscopic conductances in planar lipid bilayers. The conductances were highly sensitive to pH: their induction required acidic pH (pH 5.3), but their magnitude could be increased 3,000-fold upon alkalinization of the milieu (pK ₐ = 7.1). We show that this phenomenon can be attributed to the association of APOL1 with the bilayer at acidic pH, followed by the opening of APOL1-induced cation-selective channels upon pH neutralization. Furthermore, the conductance increase at neutral pH (but not membrane association at acidic pH) was prevented by the interaction of APOL1 with the serum resistance-associated protein, which is produced by T. brucei rhodesiense and prevents trypanosome lysis by APOL1. These data are consistent with a model of lysis that involves endocytic recycling of APOL1 and the formation of cation-selective channels, at neutral pH, in the parasite plasma membrane.
Integrating abundance and functional traits reveals new global hotspots of fish diversity
Global reef fish diversity is studied with metrics incorporating species abundances and functional traits; these identify diversity hotspots corresponding to the diversity of functional traits amongst individuals in the community, and greater evenness in the abundance of reef fishes at higher latitudes, findings that contrast with patterns reported previously using traditional richness-based methods. Cooler biodiversity hotspots revealed Traditional measures of biodiversity record species richness across different areas — in other words, they just count the number of species. This approach takes no account of the fact that different species will have different abundances, or that the range of functional traits present in a community is not dependent solely on the number of species. This paper presents a new measure of functional diversity, incorporating species abundances and functional traits into a global census of a vertebrate group —2,473 marine reef fish species — at 1,844 sites. The results reveal previously unknown diversity hotspots in temperate regions and in the Tropical Eastern Pacific, which are outside the species-rich tropical regions traditionally associated with high biodiversity. Species richness has dominated our view of global biodiversity patterns for centuries 1 , 2 . The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management 3 , 4 . However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling) 5 . Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao’s Q 6 ), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only 7 , 8 . There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites (‘community evenness’), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness 2 , 4 . Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.
Consistent multi-level trophic effects of marine reserve protection across northern New Zealand
Investigates whether a system of no-take marine reserves generates consistent biodiversity outcomes, based on systematic Reef Life Survey censuses of rocky reef fishes, invertebrates and macroalgae at eight marine reserves across northern NZ and the Kermadec Islands. Assesses ecological responses of reef assemblages to protection from fishing, including potential trophic cascades, using a control-impact design for the six marine reserves studied with associated reference sites, and also by comparing observations at reserve sites with predictions from random forest models that assume reserve locations are fished. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Multiple lifestyle factors and depressed mood: a cross-sectional and longitudinal analysis of the UK Biobank (N = 84,860)
Background There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as ‘healthy controls’ (HC). Methods To this end, we assessed the relationships between 6 key lifestyle factors (measured via self-report) and depressed mood (measured via a relevant item from the Patient Health Questionnaire) in individuals with a history of or current MDD and healthy controls (HCs). Cross-sectional analyses were performed in the UK Biobank baseline sample, and longitudinal analyses were conducted in those who completed the Mental Health Follow-up. Results Cross-sectional analysis of 84,860 participants showed that in both MDD and HCs, physical activity, healthy diet, and optimal sleep duration were associated with less frequency of depressed mood (all p  < 0.001; ORs 0.62 to 0.94), whereas screen time and also tobacco smoking were associated with higher frequency of depressed mood (both p  < 0.0001; ORs 1.09 to 1.36). In the longitudinal analysis, the lifestyle factors which were protective of depressed mood in both MDD and HCs were optimal sleep duration (MDD OR = 1.10; p  < 0.001, HC OR = 1.08; p  < 0.001) and lower screen time (MDD OR = 0.71; p  < 0.001, HC OR = 0.80; p  < 0.001). There was also a significant interaction between healthy diet and MDD status ( p  = 0.024), while a better-quality diet was indicated to be protective of depressed mood in HCs (OR = 0.92; p  = 0.045) but was not associated with depressed mood in the MDD sample. In a cross-sectional (OR = 0.91; p  < 0.0001) analysis, higher frequency of alcohol consumption was surprisingly associated with reduced frequency of depressed mood in MDD, but not in HCs. Conclusions Our data suggest that several lifestyle factors are associated with depressed mood, and in particular, it calls into consideration habits involving increased screen time and a poor sleep and dietary pattern as being partly implicated in the germination or exacerbation of depressed mood.
Apolipoprotein L-1 renal risk variants form active channels at the plasma membrane driving cytotoxicity
Recently evolved alleles of Apolipoprotein L-1 ( APOL1 ) provide increased protection against African trypanosome parasites while also significantly increasing the risk of developing kidney disease in humans. APOL1 protects against trypanosome infections by forming ion channels within the parasite, causing lysis. While the correlation to kidney disease is robust, there is little consensus concerning the underlying disease mechanism. We show in human cells that the APOL1 renal risk variants have a population of active channels at the plasma membrane, which results in an influx of both Na + and Ca 2+ . We propose a model wherein APOL1 channel activity is the upstream event causing cell death, and that the activate-state, plasma membrane-localized channel represents the ideal drug target to combat APOL1-mediated kidney disease.
Global conservation outcomes depend on marine protected areas with five key features
Marine protected areas (MPAs) are an important and increasing component of marine conservation strategy, but their effectiveness is variable and debated; now a study has assembled data from a global sample of MPAs and demonstrates that effectiveness depends on five key properties: whether any fishing is allowed, enforcement levels, age, size and degree of isolation. Five steps to marine protection Marine protected areas are an important and increasing component of marine conservation strategy, but their effectiveness is variable and much debated. These authors assemble data from a global sample of fished regions and 87 marine protected areas and demonstrate that the effectiveness of a protected area depends on five key properties: how much fishing is allowed, enforcement levels, how long protection has been in place, area and degree of isolation. Conservation is assured only when all five of these boxes have been ticked. In line with global targets agreed under the Convention on Biological Diversity, the number of marine protected areas (MPAs) is increasing rapidly, yet socio-economic benefits generated by MPAs remain difficult to predict and under debate 1 , 2 . MPAs often fail to reach their full potential as a consequence of factors such as illegal harvesting, regulations that legally allow detrimental harvesting, or emigration of animals outside boundaries because of continuous habitat or inadequate size of reserve 3 , 4 , 5 . Here we show that the conservation benefits of 87 MPAs investigated worldwide increase exponentially with the accumulation of five key features: no take, well enforced, old (>10 years), large (>100 km 2 ), and isolated by deep water or sand. Using effective MPAs with four or five key features as an unfished standard, comparisons of underwater survey data from effective MPAs with predictions based on survey data from fished coasts indicate that total fish biomass has declined about two-thirds from historical baselines as a result of fishing. Effective MPAs also had twice as many large (>250 mm total length) fish species per transect, five times more large fish biomass, and fourteen times more shark biomass than fished areas. Most (59%) of the MPAs studied had only one or two key features and were not ecologically distinguishable from fished sites. Our results show that global conservation targets based on area alone will not optimize protection of marine biodiversity. More emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.
Reef Fishes at All Trophic Levels Respond Positively to Effective Marine Protected Areas
Marine Protected Areas (MPAs) offer a unique opportunity to test the assumption that fishing pressure affects some trophic groups more than others. Removal of larger predators through fishing is often suggested to have positive flow-on effects for some lower trophic groups, in which case protection from fishing should result in suppression of lower trophic groups as predator populations recover. We tested this by assessing differences in the trophic structure of reef fish communities associated with 79 MPAs and open-access sites worldwide, using a standardised quantitative dataset on reef fish community structure. The biomass of all major trophic groups (higher carnivores, benthic carnivores, planktivores and herbivores) was significantly greater (by 40% - 200%) in effective no-take MPAs relative to fished open-access areas. This effect was most pronounced for individuals in large size classes, but with no size class of any trophic group showing signs of depressed biomass in MPAs, as predicted from higher predator abundance. Thus, greater biomass in effective MPAs implies that exploitation on shallow rocky and coral reefs negatively affects biomass of all fish trophic groups and size classes. These direct effects of fishing on trophic structure appear stronger than any top down effects on lower trophic levels that would be imposed by intact predator populations. We propose that exploitation affects fish assemblages at all trophic levels, and that local ecosystem function is generally modified by fishing.
The Combined Effect of Common Genetic Risk Variants on Circulating Lipoproteins Is Evident in Childhood: A Longitudinal Analysis of the Cardiovascular Risk in Young Finns Study
Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are modifiable risk factors for cardiovascular disease. Several genetic loci for predisposition to abnormal LDL-C, HDL-C and TG have been identified. However, it remains unclear whether these loci are consistently associated with serum lipid levels at each age or with unique developmental trajectories. Therefore, we assessed the association between genome wide association studies (GWAS) derived polygenic genetic risk scores and LDL-C, HDL-C, and triglyceride trajectories from childhood to adulthood using data available from the 27-year European 'Cardiovascular Risk in Young Finns' Study. For 2,442 participants, three weighted genetic risk scores (wGRSs) for HDL-C (38 SNPs), LDL-C (14 SNPs) and triglycerides (24 SNPs) were computed and tested for association with serum lipoprotein levels measured up to 8 times between 1980 and 2011. The categorical analyses revealed no clear divergence of blood lipid trajectories over time between wGRSs categories, with participants in the lower wGRS quartiles tending to have average lipoprotein concentrations 30 to 45% lower than those in the upper-quartile wGRS beginning at age 3 years and continuing through to age 49 years (where the upper-quartile wGRS have 4-7 more risk alleles than the lower wGRS group). Continuous analyses, however, revealed a significant but moderate time-dependent genetic interaction for HDL-C levels, with the association between HDL-C and the continuous HDL-C risk score weakening slightly with age. Conversely, in males, the association between the continuous TG genetic risk score and triglycerides levels tended to be lower in childhood and become more pronounced after the age of 25 years. Although the influence of genetic factors on age-specific lipoprotein values and developmental trajectories is complex, our data show that wGRSs are highly predictive of HDL-C, LDL-C, and triglyceride levels at all ages.
A global assessment of the direct and indirect benefits of marine protected areas for coral reef conservation
Aim Marine protected areas (MPAs) are increasingly implemented to conserve or restore coral reef biodiversity, yet evidence of their benefits for enhancing coral cover is limited and variable. Location 30 MPAs worldwide and nearby sites (within 10 km). Taxa Cover of key functional groups for coral (total, branching, massive and tabular), and algae (total, filamentous, foliose) and total biomass of reef fish trophic groups (excavator, scraper, browser, higher carnivore). Methods We used a global dataset obtained using standardized survey methods at 465 sites associated with 30 MPAs in 28 ecoregions to test the effects of five key MPA attributes (>10 years old, well‐enforced, no‐take, large and isolated) on coral cover, algal cover and reef fish biomass. We also tested the direct (reducing disturbance by human activities) versus indirect pathways (increasing grazing potential through recovering populations of herbivorous fishes) by which MPAs can influence coral and algal cover. Results Only well‐enforced, no‐take and old (>10 years) MPAs had higher total coral cover (response ratio 1.08–1.19×) than fished sites, mostly due to the increased cover of massive coral growth forms (1.34–2.06×). This effect arose through both the direct influence of protection and indirect benefits of depressed algal cover by recovering herbivorous fish biomass. Neither the direct (standardized coefficient = 0.06) nor indirect effects (standardized coefficient = 0.04) of no‐take protection on coral cover were particularly strong, likely reflecting regional differences in fishing gear, targeted species and trophic webs. Conclusions MPAs promote the persistence of some functional groups of corals, and thus represent an important management tool, globally.
Assessing National Biodiversity Trends for Rocky and Coral Reefs through the Integration of Citizen Science and Scientific Monitoring Programs
Reporting progress against targets for international biodiversity agreements is hindered by a shortage of suitable biodiversity data. We describe a cost-effective system involving Reef Life Survey citizen scientists in the systematic collection of quantitative data covering multiple phyla that can underpin numerous marine biodiversity indicators at high spatial and temporal resolution. We then summarize the findings of a continental- and decadal-scale State of the Environment assessment for rocky and coral reefs based on indicators of ecosystem state relating to fishing, ocean warming, and invasive species and describing the distribution of threatened species. Fishing impacts are widespread, whereas substantial warming-related change affected some regions between 2005 and 2015. Invasive species are concentrated near harbors in southeastern Australia, and the threatened-species index is highest for the Great Australian Bight and Tasman Sea. Our approach can be applied globally to improve reporting against biodiversity targets and enhance public and policymakers’ understanding of marine biodiversity trends.