Joint effect of phosphorus limitation and temperature on alkaline phosphatase activity and somatic growth in Daphnia magna

Alkaline phosphatase (AP) is a potential biomarker for phosphorus (P) limitation in zooplankton. However, knowledge about regulation of AP in this group is limited. In a laboratory acclimation experiment, we investigated changes in body AP concentration for Daphnia magna kept for 6 days at 10, 15, 20 and 25°C and fed algae with 10 different molar C:P ratios (95–660). In the same experiment, we also assessed somatic growth of the animals since phosphorus acquisition is linked to growth processes. Overall, non-linear but significant relationships of AP activity with C:P ratio were observed, but there was a stronger impact of temperature on AP activity than of P limitation. Animals from the lowest temperature treatment had higher normalized AP activity, which suggests the operation of biochemical temperature compensation mechanisms. Body AP activity increased by a factor of 1.67 for every 10°C decrease in temperature. These results demonstrate that temperature strongly influences AP expression. Therefore, using AP as a P limitation marker in zooplankton needs to consider possible confounding effects of temperature. Both temperature and diet affected somatic growth. The temperature effect on somatic growth, expressed as the Q10 value, responded non-linearly with C:P, with Q10 ranging between 1.9 for lowest food C:P ratio and 1.4 for the most P-deficient food. The significant interaction between those two variables highlights the importance of studying temperature-dependent changes of growth responses to food quality

Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe

Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes in Schizosaccharomyces pombe. This association is RNase sensitive, correlates with Pol II transcription and mRNA expression levels. Changes in Pol II occupancy were detected in a Upf1 deficient (upf1∆) strain, prevalently at genes showing a high Upf1 relative to Pol II association in wild-type. Additionally, an increased Ser2 Pol II signal was detected at all highly transcribed genes examined by ChIP-qPCR. Furthermore, upf1cells are hypersensitive to the transcription elongation inhibitor 6-azauracil. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated in upf1. These data envisage that by operating on the nascent transcript, Upf1 might influence Pol II phosphorylation and transcription

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Nordic Workshop on New Approach Methodologies (NAMs) : for Grouping and Read-Across under REACH and CLP

New Approach Methodologies (NAMs) are an emerging tool in toxicology for performing chemical risk assessment. NAMs reduce animal testing while increasing robustness, throughput and providing a mechanistic understanding of chemical modes-of-actions, in accordance with the Next Generation Risk Assessment principles. The workshop’s objective was to increase risk assessors’ understanding of the data produced by NAMs and their ability to use it for regulatory actions under REACH and CLP. It aimed to highlight the main challenges for NAMs, discuss possible advancements in using NAMs, and increase knowledge and competence within the relevant Nordic authorities. It also served to facilitate discussions about the obstacles to implementing NAMs in regulatory processes, and to identify strategies (including omics approaches) for increasing their use in read-across and grouping processes

Phosphorus limitation enhances parasite impact: feedback effects at the population level

Background Nutrient deficiency affects the growth and population dynamics of consumers. Endoparasites can be seen as consumers that drain carbon (C) or energy from their host while simultaneously competing for limiting resources such as phosphorus (P). Depending on the relative demands of the host and the parasite for the limiting nutrient, intensified resource competition under nutrient limitation can either reduce the parasite’s effect on the host or further reduce the fitness of the nutrient-limited host. So far, knowledge of how nutrient limitation affects parasite performance at the host population level and how this affects the host populations is limited. Results We followed the population growth of Daphnia magna that were uninfected or experimentally infected with a microsporidian, Glugoides intestinalis. The Daphnia were fed either P-sufficient or P-limited algae. The P-limited diet decreased the population density and biomass compared with the populations fed with the P-sufficient algae. In the P-sufficient populations, infection with the parasite reduced the population density but not the biomass of Daphnia, while in the P-limited populations, both the density and biomass of Daphnia decreased toward the end of the 32 day experiment compared with the uninfected controls. The infected animals from the P-limited populations had higher parasite spore cluster counts, while, in a separate experiment, host diet quality did not affect the number of parasites in individually kept Daphnia. Conclusions Because host diet quality did not affect parasite numbers at the individual level, we suggest that the higher parasite load in the P-limited populations is a result of feedback effects arising at the population level. Because of the density-dependent transmission of the parasite and the time lag between exposure and transmission, the lower host population density in the P-limited populations led to a higher spore:host ratio. This effect may have been further reinforced by decreases in filtration rates caused by crowding in the P-sufficient populations and/or increases in filtration rates as a response to poor food quality in the P-limited populations. The increases in exposure led to a higher parasite load and aggravated the negative effects of parasite infection at the population level

Data from: Phosphorus limitation enhances parasite impact: feedback effects at the population level

Background: Nutrient deficiency affects the growth and population dynamics of consumers. Endoparasites can be seen as consumers that drain carbon (C) or energy from their host while simultaneously competing for limiting resources such as phosphorus (P). Depending on the relative demands of the host and the parasite for the limiting nutrient, intensified resource competition under nutrient limitation can either reduce the parasite?s effect on the host or further reduce the fitness of the nutrient-limited host. So far, knowledge of how nutrient limitation affects parasite performance at the host population level and how this affects the host populations is limited. Results: We followed the population growth of Daphnia magna that were uninfected or experimentally infected with a microsporidian, Glugoides intestinalis. The Daphnia were fed either P-sufficient or P-limited algae. The P-limited diet decreased the population density and biomass compared with the populations fed with the P-sufficient algae. In the P-sufficient populations, infection with the parasite reduced the population density but not the biomass of Daphnia, while in the P-limited populations, both the density and biomass of Daphnia decreased toward the end of the 32?day experiment compared with the uninfected controls. The infected animals from the P-limited populations had higher parasite spore cluster counts, while, in a separate experiment, host diet quality did not affect the number of parasites in individually kept Daphnia. Conclusions: Because host diet quality did not affect parasite numbers at the individual level, we suggest that the higher parasite load in the P-limited populations is a result of feedback effects arising at the population level. Because of the density-dependent transmission of the parasite and the time lag between exposure and transmission, the lower host population density in the P-limited populations led to a higher spore:host ratio. This effect may have been further reinforced by decreases in filtration rates caused by crowding in the P-sufficient populations and/or increases in filtration rates as a response to poor food quality in the P-limited populations. The increases in exposure led to a higher parasite load and aggravated the negative effects of parasite infection at the population level

Bi-directional efects of vitamin B12 and methotrexate on Daphnia magna ftness and genomic methylation

Here we interrogated, using three separate but complementary experimental approaches, the impact of vitamin B12 availability and methotrexate exposure on Daphnia magna, which we hypothesised should have an opposite efect on One carbon metabolism (OCM). OCM is a vital biological process supporting a variety of physiological processes, including DNA methylation. Contrary to mammalian models, this process remains largely unexplored in invertebrates. The purpose of this study was to elucidate the impact of OCM short-term alteration on the ftness and epigenome of the keystone species, Daphnia. We used maternal age at reproduction, brood size and survival rates in combination with DNA methylation sensitive comet assay to determine the efects of vitamin B12 or MTX on ftness and the epigenome. Vitamin B12 had a positive infuence on Daphnia ftness and we provide evidence demonstrating that this may be associated with an increased level of genome-wide DNA methylation. Conversely, exposing D. magna to MTX negatively infuenced the ftness of the animals and was associated with loss of global DNA methylation, translating in decreased ftness. These results highlight the potential importance of OCM in invertebrates, providing novel evidence supporting a potential role for epigenetic modifcations to the genome in D. magna environmental adaptability.European Commission - Seventh Framework Programme (FP7)Norwegian Research Counci

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Next-generation sequencing of DNA from resting eggs: signatures of eutrophication in a lake's sediment

Hatching resting stages of ecologically important organisms such as Daphnia from lake sediments, referred to as resurrection ecology, is a powerful approach to assess changes in alleles and traits over time. However, the utility of the approach is constrained by a few obstacles, including low and/or biased hatching among genotypes. Here, we eliminated such bottlenecks by investigating DNA sequences isolated directly (i.e. without hatching) from resting eggs found in the sediments of Lake Constance spanning pre-, peri-, and post-eutrophication. While we expected genome-wide changes, we specifically expected changes in alleles related to pathways involved in mitigating effects of cyanobacterial toxins. We used pairwise FST-analyses to identify transcripts that showed strongest divergence among the four different populations and a clustering analysis to identify correlations between allele frequency shifts and changes in abiotic and biotic lake parameters. In a cluster that correlated with the increased abundance of cyanobacteria in Lake Constance we find genes that have been reported earlier to be differentially expressed in response to the cyanobacterial toxin microcystin and to microcystin-free cyanobacteria. We further reveal the enrichment of gene ontology terms that have been shown to be involved in microcystin-related responses in other organisms but not yet in Daphnia and as such are candidate loci for adaptation of natural Daphnia populations to increased cyanobacterial abundances. In conclusion this approach of investigating DNA extracted from Daphnia resting stages allowed to determine frequency changes of loci in a natural population over time