570 Biowissenschaften; Biologie
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Objective:
Stunting (height-for-age < −2 SD) is one of the forms of undernutrition and is frequent among children of low- and middle-income countries. But stunting perSe is not a synonym of undernutrition. We investigated association between body height and indicators of energetic undernutrition at three critical thresholds for thinness used in public health: (1) BMI SDS < −2; (2) mid-upper arm circumference divided by height (MUAC (mm) × 10/height (cm) < 1·36) and (3) mean skinfold thickness (SF) < 7 mm and to question the reliability of thresholds as indicators of undernutrition.
Design:
Cross-sectional study; breakpoint analysis.
Setting:
Rural and urban regions of Indonesia and Guatemala – different socio-economic status (SES).
Participants:
1716 Indonesian children (6·0–13·2 years) and 3838 Guatemalan children (4·0–18·9 years) with up to 50 % stunted children.
Results:
When separating the regression of BMI, MUAC or SF, on height into distinguishable segments (breakpoint analysis), we failed to detect relevant associations between height, and BMI, MUAC or SF, even in the thinnest and shortest children. For BMI and SF, the breakpoint analysis either failed to reach statistical significance or distinguished at breakpoints above critical thresholds. For MUAC, the breakpoint analysis yielded negative associations between MUAC/h and height in thin individuals. Only in high SES Guatemalan children, SF and height appeared mildly associated with R2 = 0·017.
Conclusions:
Currently used lower thresholds of height-for-age (stunting) do not show relevant associations with anthropometric indicators of energetic undernutrition. We recommend using the catch-up growth spurt during early re-feeding instead as immediate and sensitive indicator of past undernourishment. We discuss the primacy of education and social-economic-political-emotional circumstances as responsible factors for stunting.
What Colin Reynolds could tell us about nutrient limitation, N:P ratios and eutrophication control
(2020)
Colin Reynolds exquisitely consolidated our understanding of driving forces shaping phytoplankton communities and those setting the upper limit to biomass yield, with limitation typically shifting from light in winter to phosphorus in spring. Nonetheless, co-limitation is frequently postulated from enhanced growth responses to enrichments with both N and P or from N:P ranging around the Redfield ratio, concluding a need to reduce both N and P in order to mitigate eutrophication. Here, we review the current understanding of limitation through N and P and of co-limitation. We conclude that Reynolds is still correct: (i) Liebig's law of the minimum holds and reducing P is sufficient, provided concentrations achieved are low enough; (ii) analyses of nutrient limitation need to exclude evidently non-limiting situations, i.e. where soluble P exceeds 3-10 mu g/l, dissolved N exceeds 100-130 mu g/l and total P and N support high biomass levels with self-shading causing light limitation; (iii) additionally decreasing N to limiting concentrations may be useful in specific situations (e.g. shallow waterbodies with high internal P and pronounced denitrification); (iv) management decisions require local, situation-specific assessments. The value of research on stoichiometry and co-limitation lies in promoting our understanding of phytoplankton ecophysiology and community ecology.
Forage availability has been suggested as one driver of the observed decline in honey bees. However, little is known about the effects of its spatiotemporal variation on colony success. We present a modeling framework for assessing honey bee colony viability in cropping systems. Based on two real farmland structures, we developed a landscape generator to design cropping systems varying in crop species identity, diversity, and relative abundance. The landscape scenarios generated were evaluated using the existing honey bee colony model BEEHAVE, which links foraging to in-hive dynamics. We thereby explored how different cropping systems determine spatiotemporal forage availability and, in turn, honey bee colony viability (e.g., time to extinction, TTE) and resilience (indicated by, e.g., brood mortality). To assess overall colony viability, we developed metrics,P(H)andP(P,)which quantified how much nectar and pollen provided by a cropping system per year was converted into a colony's adult worker population. Both crop species identity and diversity determined the temporal continuity in nectar and pollen supply and thus colony viability. Overall farmland structure and relative crop abundance were less important, but details mattered. For monocultures and for four-crop species systems composed of cereals, oilseed rape, maize, and sunflower,P(H)andP(P)were below the viability threshold. Such cropping systems showed frequent, badly timed, and prolonged forage gaps leading to detrimental cascading effects on life stages and in-hive work force, which critically reduced colony resilience. Four-crop systems composed of rye-grass-dandelion pasture, trefoil-grass pasture, sunflower, and phacelia ensured continuous nectar and pollen supply resulting in TTE > 5 yr, andP(H)(269.5 kg) andP(P)(108 kg) being above viability thresholds for 5 yr. Overall, trefoil-grass pasture, oilseed rape, buckwheat, and phacelia improved the temporal continuity in forage supply and colony's viability. Our results are hypothetical as they are obtained from simplified landscape settings, but they nevertheless match empirical observations, in particular the viability threshold. Our framework can be used to assess the effects of cropping systems on honey bee viability and to develop land-use strategies that help maintain pollination services by avoiding prolonged and badly timed forage gaps.
The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0 center dot 45-0 center dot 58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0 center dot 62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0 center dot 62 and r(traditional Mediterranean Diet Score (tMDS)) 0 center dot 51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0 center dot 70). The predefined DP correlated moderately (r 0 center dot 40-0 center dot 60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.
Role of diversification rates and evolutionary history as a driver of plant naturalization success
(2020)
Human introductions of species beyond their natural ranges and their subsequent establishment are defining features of global environmental change. However, naturalized plants are not uniformly distributed across phylogenetic lineages, with some families contributing disproportionately more to the global alien species pool than others. Additionally, lineages differ in diversification rates, and high diversification rates have been associated with characteristics that increase species naturalization success. Here, we investigate the role of diversification rates in explaining the naturalization success of angiosperm plant families.
We use five global data sets that include native and alien plant species distribution, horticultural use of plants, and a time-calibrated angiosperm phylogeny. Using phylogenetic generalized linear mixed models, we analysed the effect of diversification rate, different geographical range measures, and horticultural use on the naturalization success of plant families.
We show that a family's naturalization success is positively associated with its evolutionary history, native range size, and economic use. Investigating interactive effects of these predictors shows that native range size and geographic distribution additionally affect naturalization success. High diversification rates and large ranges increase naturalization success, especially of temperate families.
We suggest this may result from lower ecological specialization in temperate families with large ranges, compared with tropical families with smaller ranges.
Global biodiversity is under high and rising anthropogenic pressure. Yet, how the taxonomic, phylogenetic, and functional facets of biodiversity are affected by different threats over time is unclear. This is particularly true for the two main drivers of the current biodiversity crisis: habitat destruction and overexploitation. We provide the first long-term assessment of multifaceted biodiversity changes caused by these threats for any tropical region. Focussing on larger mammals in South America's 1.1 million km(2) Gran Chaco region, we assessed changes in multiple biodiversity facets between 1985 and 2015, determined which threats drive those changes, and identified remaining key areas for all biodiversity facets. Using habitat and threat maps, we found, first, that between 1985 and 2015 taxonomic (TD), phylogenetic (PD) and functional (FD) diversity all declined drastically across over half of the area assessed. FD declined about 50% faster than TD and PD, and these declines were mainly driven by species loss, rather than species turnover. Second, habitat destruction, hunting, and both threats together contributed similar to 57%, similar to 37%, and similar to 6% to overall facet declines, respectively. However, hunting pressure increased where TD and PD declined most strongly, whereas habitat destruction disproportionally contributed to FD declines. Third, just 23% of the Chaco would have to be protected to safeguard the top 17% of all three facets. Our findings uncover a widespread impoverishment of mammal species richness, evolutionary history, and ecological functions across broad areas of the Chaco due to increasing habitat destruction and hunting. Moreover, our results pinpoint key areas that should be preserved and managed to maintain all facets of mammalian diversity across the Chaco. More generally, our work highlights how long-term changes in biodiversity facets can be assessed and attributed to specific threats, to better understand human impacts on biodiversity and to guide conservation planning to mitigate them.
Invasive species frequently differentiate phenotypically in novel environments within a few generations, often even with limited genetic variation. For the invasive plants Solidago canadensis and S. gigantea, we tested whether such differentiation might have occurred through heritable epigenetic changes in cytosine methylation. In a 2-year common-garden experiment, we grew plants from seeds collected along a latitudinal gradient in their non-native Central European range to test for trait differentiation and whether differentiation disappeared when seeds were treated with the demethylation agent zebularine. Microsatellite markers revealed no population structure along the latitudinal gradient in S. canadensis, but three genetic clusters in S. gigantea. Solidago canadensis showed latitudinal clines in flowering phenology and growth. In S. gigantea, the number of clonal offspring decreased with latitude. Although zebularine had a significant effect on early growth, probably through effects on cytosine methylation, latitudinal clines remained (or even got stronger) in plants raised from seeds treated with zebularine. Thus, our experiment provides no evidence that epigenetic mechanisms by selective cytosine methylation contribute to the observed phenotypic differentiation in invasive goldenrods in Central Europe.
Trehalose 6-phosphate (Tre6P) is a sucrose signalling metabolite that has been implicated in regulation of shoot branching, but its precise role is not understood.
We expressed tagged forms of TREHALOSE-6-PHOSPHATE SYNTHASE1 (TPS1) to determine where Tre6P is synthesized in arabidopsis (Arabidopsis thaliana), and investigated the impact of localized changes in Tre6P levels, in axillary buds or vascular tissues, on shoot branching in wild-type and branching mutant backgrounds.
TPS1 is expressed in axillary buds and the subtending vasculature, as well as in the leaf and stem vasculature. Expression of a heterologous Tre6P phosphatase (TPP) to lower Tre6P in axillary buds strongly delayed bud outgrowth in long days and inhibited branching in short days. TPP expression in the vasculature also delayed lateral bud outgrowth and decreased branching. Increased Tre6P in the vasculature enhanced branching and was accompanied by higher expression of FLOWERING LOCUS T (FT) and upregulation of sucrose transporters. Increased vascular Tre6P levels enhanced branching in branched1 but not in ft mutant backgrounds.
These results provide direct genetic evidence of a local role for Tre6P in regulation of axillary bud outgrowth within the buds themselves, and also connect Tre6P with systemic regulation of shoot branching via FT.
Ecosystems with highly pulsed water supply must be better understood as climate change may increase frequency and severity of intense storms, droughts and floods. Here we collected data over 3 years (2016-2018) in the episodic wetland outflow channel (Aluize), Banhine National Park, in which the system state changed from dry to wet to dry. Field sampling included vegetation records, small-scale vegetation zoning, the seed bank and water and soil quality. The same main plant species were found in both dry and wet conditions across the riverbed of the outflow channel. We found only very few diaspores of plants in the soil after prolonged drought. In the subsequent flooded state, we examined very dense vegetation on the water surface, which was dominated by the gramineous species Paspalidium obtusifolium. This species formed a compact floating mat that was rooted to the riverbed. The Cyperaceae Bolboschoenus glaucus showed high clonal growth in the form of root tubers, which likely serve as important food reservoir during drought. Soil and water analyses do not indicate a limitation by nutrients. We outline how resident people may change the plant community structure with an increasing practice of setting fire to the meadows in the dried-up riverbed to facilitate plant regrowth as food for their livestock.
The shape of a defense-growth trade-off governs seasonal trait dynamics in natural phytoplankton
(2020)
Theory predicts that trade-offs, quantifying costs of functional trait adjustments, crucially affect community trait adaptation to altered environmental conditions, but empirical verification is scarce. We evaluated trait dynamics (antipredator defense, maximum growth rate, and phosphate affinity) of a lake phytoplankton community in a seasonally changing environment, using literature trait data and 21 years of species-resolved high-frequency biomass measurements. The trait data indicated a concave defense-growth trade-off, promoting fast-growing species with intermediate defense. With seasonally increasing grazing pressure, the community shifted toward higher defense levels at the cost of lower growth rates along the trade-off curve, while phosphate affinity explained some deviations from it. We discuss how low fitness differences of species, inferred from model simulations, in concert with stabilizing mechanisms, e.g., arising from further trait dimensions, may lead to the observed phytoplankton diversity. In conclusion, quantifying trade-offs is key for predictions of community trait adaptation and biodiversity under environmental change.
Studies on the diversity, distribution and ecological role of Saprolegniales (Oomycota) in freshwater ecosystems are currently receiving attention due to a greater understanding of their role in carbon cycling in various aquatic ecosystems. In this study, we characterized several Saprolegniales species isolated from Anzali lagoon, Gilan province, Iran, using morphological and molecular methods. Four species of Saprolegnia were identified, including S. anisospora and S. diclina as first reports for Iran, as well as Achlya strains, which were closely related to A. bisexualis, A. debaryana and A. intricata. Evaluation of the ligno-, cellulo- and chitinolytic activities was performed using plate assay methods. Most of the Saprolegniales isolates were obtained in autumn, and nearly 50% of the strains showed chitinolytic and cellulolytic activities. However, only a few Saprolegniales strains showed lignolytic activities. This study has important implications for better understanding the ecological niche of oomycetes, and to differentiate them from morphologically similar, but functionally different aquatic fungi in freshwater ecosystems.
Adverse environmental conditions are detrimental to plant growth and development. Acclimation to abiotic stress conditions involves activation of signaling pathways which often results in changes in gene expression via networks of transcription factors (TFs). Mediator is a highly conserved co-regulator complex and an essential component of the transcriptional machinery in eukaryotes. Some Mediator subunits have been implicated in stress-responsive signaling pathways; however, much remains unknown regarding the role of plant Mediator in abiotic stress responses. Here, we use RNA-seq to analyze the transcriptional response of Arabidopsis thaliana to heat, cold and salt stress conditions. We identify a set of common abiotic stress regulons and describe the sequential and combinatorial nature of TFs involved in their transcriptional regulation. Furthermore, we identify stress-specific roles for the Mediator subunits MED9, MED16, MED18 and CDK8, and putative TFs connecting them to different stress signaling pathways. Our data also indicate different modes of action for subunits or modules of Mediator at the same gene loci, including a co-repressor function for MED16 prior to stress. These results illuminate a poorly understood but important player in the transcriptional response of plants to abiotic stress and identify target genes and mechanisms as a prelude to further biochemical characterization.
Being born large for gestational age is associated with increased global placental DNA methylation
(2020)
Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001).
Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.
Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone.
Methods: Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (mu CT) for changes in trabecular and cortical architecture and mass.
Results: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture.
Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary.
Metagenomic sequencing has revolutionised our knowledge of virus diversity, with new virus sequences being reported faster than ever before. However, virus discovery from metagenomic sequencing usually depends on detectable homology: without a sufficiently close relative, so-called ‘dark’ virus sequences remain unrecognisable. An alternative approach is to use virus-identification methods that do not depend on detecting homology, such as virus recognition by host antiviral immunity. For example, virus-derived small RNAs have previously been used to propose ‘dark’ virus sequences associated with the Drosophilidae (Diptera). Here, we combine published Drosophila data with a comprehensive search of transcriptomic sequences and selected meta-transcriptomic datasets to identify a completely new lineage of segmented positive-sense single-stranded RNA viruses that we provisionally refer to as the Quenyaviruses. Each of the five segments contains a single open reading frame, with most encoding proteins showing no detectable similarity to characterised viruses, and one sharing a small number of residues with the RNA-dependent RNA polymerases of single- and double-stranded RNA viruses. Using these sequences, we identify close relatives in approximately 20 arthropods, including insects, crustaceans, spiders, and a myriapod. Using a more conserved sequence from the putative polymerase, we further identify relatives in meta-transcriptomic datasets from gut, gill, and lung tissues of vertebrates, reflecting infections of vertebrates or of their associated parasites. Our data illustrate the utility of small RNAs to detect viruses with limited sequence conservation, and provide robust evidence for a new deeply divergent and phylogenetically distinct RNA virus lineage.
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
The prevalence of vitamin A deficiency in sub-Saharan Africa necessitates effective approaches to improve provitamin A content of major staple crops. Cassava holds much promise for food security in sub-Saharan Africa, but a negative correlation between beta-carotene, a provitamin A carotenoid, and dry matter content has been reported, which poses a challenge to cassava biofortification by conventional breeding. To identify suitable material for genetic transformation in tissue culture with the overall aim to increase beta-carotene and maintain starch content as well as better understand carotenoid composition, root and leaf tissues from thirteen field-grown cassava landraces were analyzed for agronomic traits, carotenoid, chlorophyll, and starch content. The expression of five genes related to carotenoid biosynthesis were determined in selected landraces. Analysis revealed a weak negative correlation between starch and beta-carotene content, whereas there was a strong positive correlation between root yield and many carotenoids including beta-carotene. Carotenoid synthesis genes were expressed in both white and yellow cassava roots, but phytoene synthase 2 (PSY2), lycopene-epsilon-cyclase (LCY epsilon), and beta-carotenoid hydroxylase (CHY beta) expression were generally higher in yellow roots. This study identified lines with reasonably high content of starch and beta-carotene that could be candidates for biofortification by further breeding or plant biotechnological means.
Under an ecological speciation scenario, the radiation of African weakly electric fish (genus Campylomormyrus) is caused by an adaptation to different food sources, associated with diversification of the electric organ discharge (EOD). This study experimentally investigates a phenotype-environment correlation to further support this scenario. Our behavioural experiments showed that three sympatric Campylomormyrus species with significantly divergent snout morphology differentially react to variation in substrate structure. While the short snout species (C. tamandua) exhibits preference to sandy substrate, the long snout species (C. rhynchophorus) significantly prefers a stone substrate for feeding. A third species with intermediate snout size (C. compressirostris) does not exhibit any substrate preference. This preference is matched with the observation that long-snouted specimens probe deeper into the stone substrate, presumably enabling them to reach prey more distant to the substrate surface. These findings suggest that the diverse feeding apparatus in the genus Campylomormyrus may have evolved in adaptation to specific microhabitats, i.e., substrate structures where these fish forage. Whether the parallel divergence in EOD is functionally related to this adaptation or solely serves as a prezygotic isolation mechanism remains to be elucidated.
In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop.
Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers
(2020)
Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.
Pollen records from Siberia are mostly absent in global or Northern Hemisphere synthesis works. Here we present a taxonomically harmonized and temporally standardized pollen dataset that was synthesized using 173 palynological records from Siberia and adjacent areas (northeastern Asia, 42-75 degrees N, 50-180 degrees E). Pollen data were taxonomically harmonized, i.e. the original 437 taxa were assigned to 106 combined pollen taxa. Age-depth models for all records were revised by applying a constant Bayesian age-depth modelling routine. The pollen dataset is available as count data and percentage data in a table format (taxa vs. samples), with age information for each sample. The dataset has relatively few sites covering the last glacial period between 40 and 11.5 ka (calibrated thousands of years before 1950 CE) particularly from the central and western part of the study area. In the Holocene period, the dataset has many sites from most of the area, with the exception of the central part of Siberia. Of the 173 pollen records, 81 % of pollen counts were downloaded from open databases (GPD, EPD, PANGAEA) and 10 % were contributions by the original data gatherers, while a few were digitized from publications. Most of the pollen records originate from peatlands (48 %) and lake sediments (33 %). Most of the records (83 %) have >= 3 dates, allowing the establishment of reliable chronologies. The dataset can be used for various purposes, including pollen data mapping (example maps for Larix at selected time slices are shown) as well as quantitative climate and vegetation reconstructions. The datasets for pollen counts and pollen percentages are available at https://doi.org/10.1594/PANGAEA.898616 (Cao et al., 2019a), also including the site information, data source, original publication, dating data, and the plant functional type for each pollen taxa.
External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic responses. Here, we aim to address differential epigenetic responses on a gene and gene pathway level in two organs, liver and testis. We chose these organs, because the liver is the main metabolic and thermoregulation organ, and epigenetic modifications in testis are potentially transmitted to the F2 generation. We focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to an ambient temperature increase of 10 degrees C, and investigated differential methylated regions of sons sired before and after the paternal exposure using Reduced Representation Bisulfite Sequencing. We detected both a highly tissue-specific epigenetic response, reflected in genes involved in organ-specific metabolic pathways, and a more general regulation of single genes epigenetically modified in both organs. We conclude that genomes are context-specifically differentially epigenetically regulated in response to temperature increase. These findings emphasize the epigenetic relevance in cell differentiation, which is essential for the specific function(s) of complex organs, and is represented in a diverse molecular regulation of genes and gene pathways. The results also emphasize the paternal contribution to adaptive processes.
Tre6P synthesis by TPS1 is essential for embryogenesis and postembryonic growth in Arabidopsis, and appropriate Suc signaling by Tre6P is dependent on the noncatalytic domains of TPS1. In Arabidopsis (Arabidopsis thaliana), TREHALOSE-6-PHOSPHATE SYNTHASE1 (TPS1) catalyzes the synthesis of the sucrose-signaling metabolite trehalose 6-phosphate (Tre6P) and is essential for embryogenesis and normal postembryonic growth and development. To understand its molecular functions, we transformed the embryo-lethal tps1-1 null mutant with various forms of TPS1 and with a heterologous TPS (OtsA) from Escherichia coli, under the control of the TPS1 promoter, and tested for complementation. TPS1 protein localized predominantly in the phloem-loading zone and guard cells in leaves, root vasculature, and shoot apical meristem, implicating it in both local and systemic signaling of Suc status. The protein is targeted mainly to the nucleus. Restoring Tre6P synthesis was both necessary and sufficient to rescue the tps1-1 mutant through embryogenesis. However, postembryonic growth and the sucrose-Tre6P relationship were disrupted in some complementation lines. A point mutation (A119W) in the catalytic domain or truncating the C-terminal domain of TPS1 severely compromised growth. Despite having high Tre6P levels, these plants never flowered, possibly because Tre6P signaling was disrupted by two unidentified disaccharide-monophosphates that appeared in these plants. The noncatalytic domains of TPS1 ensure its targeting to the correct subcellular compartment and its catalytic fidelity and are required for appropriate signaling of Suc status by Tre6P.
The biosynthesis of the molybdenum cofactor (Moco) is highly conserved among all kingdoms of life. In all molybdoenzymes containing Moco, the molybdenum atom is coordinated to a dithiolene group present in the pterin-based 6-alkyl side chain of molybdopterin (MPT). In general, the biosynthesis of Moco can be divided into four steps in in bacteria: (i) the starting point is the formation of the cyclic pyranopterin monophosphate (cPMP) from 5 '-GTP, (ii) in the second step the two sulfur atoms are inserted into cPMP leading to the formation of MPT, (iii) in the third step the molybdenum atom is inserted into MPT to form Moco and (iv) in the fourth step bis-Mo-MPT is formed and an additional modification of Moco is possible with the attachment of a nucleotide (CMP or GMP) to the phosphate group of MPT, forming the dinucleotide variants of Moco. This review presents an update on the well-characterized Moco biosynthesis in the model organism Escherichia coli including novel discoveries from the recent years.
Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.
Aim This study investigates taxonomic and phylogenetic diversity in diatom genera to evaluate assembly rules for eukaryotic microbes across the Siberian tree line. We first analysed how phylogenetic distance relates to taxonomic richness and turnover. Second, we used relatedness indices to evaluate if environmental filtering or competition influences the assemblies in space and through time. Third, we used distance-based ordination to test which environmental variables shape diatom turnover. Location Yakutia and Taymyria, Russia: we sampled 78 surface sediments and a sediment core, extending to 7,000 years before present, to capture the forest-tundra transition in space and time respectively. Taxon Arctic freshwater diatoms. Methods We applied metabarcoding to retrieve diatom diversity from surface and core sedimentary DNA. The taxonomic assignment binned sequence types (lineages) into genera and created taxonomic (abundance of lineages within different genera) and phylogenetic datasets (phylogenetic distances of lineages within different genera). Results Contrary to our expectations, we find a unimodal relationship between phylogenetic distance and richness in diatom genera. We discern a positive relationship between phylogenetic distance and taxonomic turnover in spatially and temporally distributed diatom genera. Furthermore, we reveal positive relatedness indices in diatom genera across the spatial environmental gradient and predominantly in time slices at a single location, with very few exceptions assuming effects of competition. Distance-based ordination of taxonomic and phylogenetic turnover indicates that lake environment variables, like HCO3- and water depth, largely explain diatom turnover. Main conclusion Phylogenetic and abiotic assembly rules are important in understanding the regional assembly of diatom genera across lakes in the Siberian tree line ecotone. Using a space-time approach we are able to exclude the influence of geography and elucidate that lake environmental variables primarily shape the assemblies. We conclude that some diatom genera have greater capabilities to adapt to environmental changes, whereas others will be putatively replaced or lost due to the displacement of the Arctic tundra biome under recent global warming.
Model-derived relationships between chlorophyll a (Chl-a) and nutrients and temperature have fundamental implications for understanding complex interactions among water quality measures used for lake classification, yet accuracy comparisons of different approaches are scarce. Here, we (1) compared Chl-a model performances across linear and nonlinear statistical approaches; (2) evaluated single and combined effects of nutrients, depth, and temperature as lake surface water temperature (LSWT) or altitude on Chl-a; and (3) investigated the reliability of the best water quality model across 13 lakes from perialpine and central Balkan mountain regions. Chl-a was modelled using in situ water quality data from 157 European lakes; elevation data and LSWT in situ data were complemented by remote sensing measurements. Nonlinear approaches performed better, implying complex relationships between Chl-a and the explanatory variables. Boosted regression trees, as the best performing approach, accommodated interactions among predictor variables. Chl-a-nutrient relationships were characterized by sigmoidal curves, with total phosphorus having the largest explanatory power for our study region. In comparison with LSWT, utilization of altitude, the often-used temperature surrogate, led to different influence directions but similar predictive performances. These results support utilizing altitude in models for Chl-a predictions. Compared to Chl-a observations, Chl-a predictions of the best performing approach for mountain lakes (oligotrophic-eutrophic) led to minor differences in trophic state categorizations. Our findings suggest that both models with LSWT and altitude are appropriate for water quality predictions of lakes in mountain regions and emphasize the importance of incorporating interactions among variables when facing lake management challenges.
Resilience trinity
(2020)
Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi-faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time-horizons: 1) reactive, when there is an imminent threat to ES resilience and a high pressure to act, 2) adjustive, when the threat is known in general but there is still time to adapt management and 3) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology and engineering are often implicitly focussing on provident, adjustive or reactive resilience, respectively, but these different notions of resilience and their corresponding social, ecological and economic tradeoffs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer-term management actions are not missed while urgent threats to ES are given priority.
Broad and unspecific use of antibiotics accelerates spread of resistances. Sensitive and robust pathogen detection is thus important for a more targeted application. Bacteriophages contain a large repertoire of pathogen-binding proteins. These tailspike proteins (TSP) often bind surface glycans and represent a promising design platform for specific pathogen sensors. We analysed bacteriophage Sf6 TSP that recognizes the O-polysaccharide of dysentery-causing Shigella flexneri to develop variants with increased sensitivity for sensor applications. Ligand polyrhamnose backbone conformations were obtained from 2D H-1,H-1-trNOESY NMR utilizing methine-methine and methine-methyl correlations. They agreed well with conformations obtained from molecular dynamics (MD), validating the method for further predictions. In a set of mutants, MD predicted ligand flexibilities that were in good correlation with binding strength as confirmed on immobilized S. flexneri O-polysaccharide (PS) with surface plasmon resonance. In silico approaches combined with rapid screening on PS surfaces hence provide valuable strategies for TSP-based pathogen sensor design.
The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding.
Coarse-grained molecular model for the Glycosylphosphatidylinositol anchor with and without protein
(2020)
Glycosylphosphatidylinositol (GPI) anchors are a unique class of complex glycolipids that anchor a great variety of proteins to the extracellular leaflet of plasma membranes of eukaryotic cells. These anchors can exist either with or without an attached protein called GPI-anchored protein (GPI-AP) both in vitro and in vivo. Although GPIs are known to participate in a broad range of cellular functions, it is to a large extent unknown how these are related to GPI structure and composition. Their conformational flexibility and microheterogeneity make it difficult to study them experimentally. Simplified atomistic models are amenable to all-atom computer simulations in small lipid bilayer patches but not suitable for studying their partitioning and trafficking in complex and heterogeneous membranes. Here, we present a coarse-grained model of the GPI anchor constructed with a modified version of the MARTINI force field that is suited for modeling carbohydrates, proteins, and lipids in an aqueous environment using MARTINI's polarizable water. The nonbonded interactions for sugars were reparametrized by calculating their partitioning free energies between polar and apolar phases. In addition, sugar-sugar interactions were optimized by adjusting the second virial coefficients of osmotic pressures for solutions of glucose, sucrose, and trehalose to match with experimental data. With respect to the conformational dynamics of GPI-anchored green fluorescent protein, the accessible time scales are now at least an order of magnitude larger than for the all-atom system. This is particularly important for fine-tuning the mutual interactions of lipids, carbohydrates, and amino acids when comparing to experimental results. We discuss the prospective use of the coarse-grained GPI model for studying protein-sorting and trafficking in membrane models.
We expressed Dictyostelium lamin (NE81) lacking both a functional nuclear localization signal and a CAAX-box for C-terminal lipid modification. This lamin mutant assembled into supramolecular, three-dimensional clusters in the cytosol that disassembled at the onset of mitosis and re-assembled in late telophase, thus mimicking the behavior of the endogenous protein. As disassembly is regulated by CDK1-mediated phosphorylation at serine 122, we generated a phosphomimetic S122E mutant called GFP-NE81-S122E-∆NLS∆CLIM. Surprisingly, during imaging, the fusion protein assembled into cytosolic clusters, similar to the protein lacking the phosphomimetic mutation. Clusters disassembled again in the darkness. Assembly could be induced with blue but not green or near ultraviolet light, and it was independent of the fusion tag. Assembly similarly occurred upon cell flattening. Earlier reports and own observations suggested that both blue light and cell flattening could result in a decrease of intracellular pH. Indeed, keeping the cells at low pH also reversibly induced cluster formation. Our results indicate that lamin assembly can be induced by various stress factors and that these are transduced via intracellular acidification. Although these effects have been shown in a phosphomimetic CDK1 mutant of the Dictyostelium lamin, they are likely relevant also for wild-type lamin.
Island disharmony refers to the biased representation of higher taxa on islands compared to their mainland source regions and represents a central concept in island biology. Here, we develop a generalizable framework for approximating these source regions and conduct the first global assessment of island disharmony and its underlying drivers. We compiled vascular plant species lists for 178 oceanic islands and 735 mainland regions. Using mainland data only, we modelled species turnover as a function of environmental and geographic distance and predicted the proportion of shared species between each island and mainland region. We then quantified the over- or under-representation of families on individual islands (representational disharmony) by contrasting the observed number of species against a null model of random colonization from the mainland source pool, and analysed the effects of six family-level functional traits on the resulting measure. Furthermore, we aggregated the values of representational disharmony per island to characterize overall taxonomic bias of a given flora (compositional disharmony), and analysed this second measure as a function of four island biogeographical variables. Our results indicate considerable variation in representational disharmony both within and among plant families. Examples of generally over-represented families include Urticaceae, Convolvulaceae and almost all pteridophyte families. Other families such as Asteraceae and Orchidaceae were generally under-represented, with local peaks of over-representation in known radiation hotspots. Abiotic pollination and a lack of dispersal specialization were most strongly associated with an insular over-representation of families, whereas other family-level traits showed minor effects. With respect to compositional disharmony, large, high-elevation islands tended to have the most disharmonic floras. Our results provide important insights into the taxon- and island-specific drivers of disharmony. The proposed framework allows overcoming the limitations of previous approaches and provides a quantitative basis for incorporating functional and phylogenetic approaches into future studies of island disharmony.
Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans
(2020)
Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence.
Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication.
Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low.
Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
Research publications and data nowadays should be publicly available on the internet and, theoretically, usable for everyone to develop further research, products, or services. The long-term accessibility of research data is, therefore, fundamental in the economy of the research production process. However, the availability of data is not sufficient by itself, but also their quality must be verifiable. Measures to ensure reuse and reproducibility need to include the entire research life cycle, from the experimental design to the generation of data, quality control, statistical analysis, interpretation, and validation of the results. Hence, high-quality records, particularly for providing a string of documents for the verifiable origin of data, are essential elements that can act as a certificate for potential users (customers). These records also improve the traceability and transparency of data and processes, therefore, improving the reliability of results. Standards for data acquisition, analysis, and documentation have been fostered in the last decade driven by grassroot initiatives of researchers and organizations such as the Research Data Alliance (RDA). Nevertheless, what is still largely missing in the life science academic research are agreed procedures for complex routine research workflows. Here, well-crafted documentation like standard operating procedures (SOPs) offer clear direction and instructions specifically designed to avoid deviations as an absolute necessity for reproducibility. Therefore, this paper provides a standardized workflow that explains step by step how to write an SOP to be used as a starting point for appropriate research documentation.
Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.
Human and murine studies identified the lysosomal enzyme acid sphingomyelinase (ASM) as a target for antidepressant therapy and revealed its role in the pathophysiology of major depression. In this study, we generated a mouse model with overexpression of Asm (Asm-tg(fb)) that is restricted to the forebrain to rule out any systemic effects of Asm overexpression on depressive-like symptoms. The increase in Asm activity was higher in male Asm-tg(fb) mice than in female Asm-tg(fb) mice due to the breeding strategy, which allows for the generation of wild-type littermates as appropriate controls. Asm overexpression in the forebrain of male mice resulted in a depressive-like phenotype, whereas in female mice, Asm overexpression resulted in a social anxiogenic-like phenotype. Ceramides in male Asm-tg(fb) mice were elevated specifically in the dorsal hippocampus. mRNA expression analyses indicated that the increase in Asm activity affected other ceramide-generating pathways, which might help to balance ceramide levels in cortical brain regions. This forebrain-specific mouse model offers a novel tool for dissecting the molecular mechanisms that play a role in the pathophysiology of major depression.
Objective
Plant carnivory is distributed across the tree of life and has evolved at least six times independently, but sequenced and annotated nuclear genomes of carnivorous plants are currently lacking. We have sequenced and structurally annotated the nuclear genome of the carnivorous Roridula gorgonias and that of a non-carnivorous relative, Madeira’s lily-of-the-valley-tree, Clethra arborea, both within the Ericales. This data adds an important resource to study the evolutionary genetics of plant carnivory across angiosperm lineages and also for functional and systematic aspects of plants within the Ericales.
Results
Our assemblies have total lengths of 284 Mbp (R. gorgonias) and 511 Mbp (C. arborea) and show high BUSCO scores of 84.2% and 89.5%, respectively. We used their predicted genes together with publicly available data from other Ericales’ genomes and transcriptomes to assemble a phylogenomic data set for the inference of a species tree. However, groups of orthologs showed a marked absence of species represented by a transcriptome. We discuss possible reasons and caution against combining predicted genes from genome- and transriptome-based assemblies.
Differentially-charged liposomes interact with alphaherpesviruses and interfere with virus entry
(2020)
Exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane is induced by infection with several members of the Alphaherpesvirinae subfamily. There is evidence that PS is used by the equine herpesvirus type 1 (EHV-1) during entry, but the exact role of PS and other phospholipids in the entry process remains unknown. Here, we investigated the interaction of differently charged phospholipids with virus particles and determined their influence on infection. Our data show that liposomes containing negatively charged PS or positively charged DOTAP (N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium) inhibited EHV-1 infection, while neutral phosphatidylcholine (PC) had no effect. Inhibition of infection with PS was transient, decreased with time, and was dose dependent. Our findings indicate that both cationic and anionic phospholipids can interact with the virus and reduce infectivity, while, presumably, acting through different mechanisms. Charged phospholipids were found to have antiviral effects and may be used to inhibit EHV-1 infection.
The other-race effect (ORE) can be described as difficulties in discriminating between faces of ethnicities other than one’s own, and can already be observed at approximately 9 months of age. Recent studies also showed that infants visually explore same-and other-race faces differently. However, it is still unclear whether infants’ looking behavior for same- and other-race faces is related to their face discrimination abilities. To investigate this question we conducted a habituation–dishabituation experiment to examine Caucasian 9-month-old infants’ gaze behavior, and their discrimination of same- and other-race faces, using eye-tracking measurements. We found that infants looked longer at the eyes of same-race faces over the course of habituation, as compared to other-race faces. After habituation, infants demonstrated a clear other-race effect by successfully discriminating between same-race faces, but not other-race faces. Importantly, the infants’ ability to discriminate between same-race faces significantly correlated with their fixation time towards the eyes of same-race faces during habituation. Thus, our findings suggest that for infants old enough to begin exhibiting the ORE, gaze behavior during habituation is related to their ability to differentiate among same-race faces, compared to other-race faces.
Luminescent Ionogels with Excellent Transparency, High Mechanical Strength, and High Conductivity
(2020)
The paper describes a new kind of ionogel with both good mechanical strength and high conductivity synthesized by confining the ionic liquid (IL) 1-butyl-3-methylimidazolium bis(trifluoromethane sulfonyl)imide ([Bmim][NTf₂]) within an organic–inorganic hybrid host. The organic–inorganic host network was synthesized by the reaction of methyltrimethoxysilane (MTMS), tetraethoxysilane (TEOS), and methyl methacrylate (MMA) in the presence of a coupling agent, offering the good mechanical strength and rapid shape recovery of the final products. The silane coupling agent 3-methacryloxypropyltrimethoxysilane (KH-570) plays an important role in improving the mechanical strength of the inorganic–organic hybrid, because it covalently connected the organic component MMA and the inorganic component SiO₂. Both the thermal stability and mechanical strength of the ionogel significantly increased by the addition of IL. The immobilization of [Bmim][NTf₂] within the ionogel provided the final ionogel with an ionic conductivity as high as ca. 0.04 S cm⁻¹ at 50 °C. Moreover, the hybrid ionogel can be modified with organosilica-modified carbon dots within the network to yield a transparent and flexible ionogel with strong excitation-dependent emission between 400 and 800 nm. The approach is, therefore, a blueprint for the construction of next-generation multifunctional ionogels.
Consensify
(2020)
A standard practise in palaeogenome analysis is the conversion of mapped short read data into pseudohaploid sequences, frequently by selecting a single high-quality nucleotide at random from the stack of mapped reads. This controls for biases due to differential sequencing coverage, but it does not control for differential rates and types of sequencing error, which are frequently large and variable in datasets obtained from ancient samples. These errors have the potential to distort phylogenetic and population clustering analyses, and to mislead tests of admixture using D statistics. We introduce Consensify, a method for generating pseudohaploid sequences, which controls for biases resulting from differential sequencing coverage while greatly reducing error rates. The error correction is derived directly from the data itself, without the requirement for additional genomic resources or simplifying assumptions such as contemporaneous sampling. For phylogenetic and population clustering analysis, we find that Consensify is less affected by artefacts than methods based on single read sampling. For D statistics, Consensify is more resistant to false positives and appears to be less affected by biases resulting from different laboratory protocols than other frequently used methods. Although Consensify is developed with palaeogenomic data in mind, it is applicable for any low to medium coverage short read datasets. We predict that Consensify will be a useful tool for future studies of palaeogenomes.
Highly luminescent indium phosphide zinc sulfide (InPZnS) quantum dots (QDs), with zinc selenide/zinc sulfide (ZnSe/ZnS) shells, were synthesized. The QDs were modified via a post-synthetic ligand exchange reaction with 3-mercaptopropionic acid (MPA) and 11-mercaptoundecanoic acid (MUA) in different MPA:MUA ratios, making this study the first investigation into the effects of mixed ligand shells on InPZnS QDs. Moreover, this article also describes an optimized method for the correlation of the QD size vs. optical absorption of the QDs. Upon ligand exchange, the QDs can be dispersed in water. Longer ligands (MUA) provide more stable dispersions than short-chain ligands. Thicker ZnSe/ZnS shells provide a better photoluminescence quantum yield (PLQY) and higher emission stability upon ligand exchange. Both the ligand exchange and the optical properties are highly reproducible between different QD batches. Before dialysis, QDs with a ZnS shell thickness of ~4.9 monolayers (ML), stabilized with a mixed MPA:MUA (mixing ratio of 1:10), showed the highest PLQY, at ~45%. After dialysis, QDs with a ZnS shell thickness of ~4.9 ML, stabilized with a mixed MPA:MUA and a ratio of 1:10 and 1:100, showed the highest PLQYs, of ~41%. The dispersions were stable up to 44 days at ambient conditions and in the dark. After 44 days, QDs with a ZnS shell thickness of ~4.9 ML, stabilized with only MUA, showed the highest PLQY, of ~34%.