Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
- MeSH
- celogenomová asociační studie * MeSH
- dítě MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- nefrotický syndrom * genetika MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Using in situ data of 2014-2018, the summers Emiliania huxleyi blooms in the Barents Sea were studied. The blooms were recorded in the upper mixed layer in July and August every year, during which they spread to cover large areas and were associated with Atlantic waters. The E. huxleyi abundance revealed interannual variability, with the highest values (up to 12 × 106 cells/L) in July 2016. Bloom is characterized by a sharp seasonal thermocline, water surface temperature of about 7.14-11.7 °C, low silicate (0.45 ± 0.08 μM) and nitrogen (0.74 ± 0.16 μM) concentration, high phosphorus concentration (0.09 ± 0.01 μM) and nitrogen to phosphorus ratio significantly below the Redfield ratio. Data confirming the hypothesis of limiting the growth of diatoms by nitrogen concentration are presented. When E. huxleyi bloomed, its biomass exceeded 70% of the total phytoplankton biomass, species diversity was low, and diatoms were practically absent, and dinoflagellates were usually represented by large species.
- MeSH
- dusík MeSH
- fosfor MeSH
- fytoplankton MeSH
- Haptophyta * MeSH
- rozsivky * MeSH
- Publikační typ
- časopisecké články MeSH
We hypothesize that algae with different cell compositions are differently perceived by their predators and consequently subjected to selective grazing. Five populations of the diatom Phaeodactylum tricornutum that differed in organic and elemental composition, but were otherwise identical, were generated by acclimation to distinct growth regimes. The different populations were then mixed in pairs and subjected to predation by either the rotifer Brachionus plicatilis or the copepod Acartia tonsa. The presence of rotifers had no impact on the ratio between any two algal populations. The presence of copepods, however, affected the ratio between algae previously acclimated to a medium containing 1 mM NH4+ and algae acclimated to 0.5 mM NO3- , and to either a lower irradiance or a higher CO2 concentration. We discuss the possible reason for the influence of different nutritional histories on the vulnerability of algae to predators. The differential impact of grazers on the growth of algae with different nutritional histories may result from direct selective grazing (i.e., grazers can detect algae with the most palatable cell composition), alone or combined to an asymmetric utilization of the nutrients regenerated after predation by co-existing algal populations. Our results strongly suggest that the nutritional history of algae can influence the relationships between phytoplankton and grazers and hint at the possibility that algal cell composition is potentially subject to natural selection, because it influences the probability that algae survive predation.
- MeSH
- Copepoda * MeSH
- fytoplankton MeSH
- rozsivky * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chromera velia is a marine photosynthetic relative of human apicomplexan parasites. It has been isolated from coral reefs and is indicted for being involved in symbioses with hermatypic corals. C. velia has been subject to intensive research, but still very little is known of its response to light quality and quantity. Here, we have studied the growth and compositional responses of C. velia to culture under monochromatic light (blue, green or red), at two photon flux densities (PFD, 20 and 100 μmol photons m-2 s-1). Our results show that C. velia growth rate is unaffected by the quality of light, whereas it responds to PFD. However, light quality influenced cell size, which was smaller for cells exposed to blue monochromatic light, regardless of PFD. PFD strongly influenced carbon allocation: at 20 μmol photons m-2 s-1, carbon was mainly allocated into proteins while at 100 μmol photons m-2 s-1, carbon was allocated mainly into carbohydrate and lipid pools. The blue light treatment caused a decrease in the lipids and carbohydrates to proteins and thus suggested to affect nitrogen metabolism in acclimated cells. Whole-cell absorption spectra revealed the existence of red-shifted chlorophyll a antenna not only under red light but in all low PFD treatments. These findings show the ability of C. velia to successfully adapt and thrive in spectrally very different environments of coral reefs.
We report the results of simple experiments which support the hypothesis that changes in ocean chemistry beginning in the Mesozoic Era resulted in an increase in the nutritional quality per mole of C and per cell of planktonic algal biomass compared to earlier phytoplankton. We cultured a cyanobacterium, a diatom, a dinoflagellate, and a green alga in media mimicking aspects of the chemistry of Palaeozoic and Mesozoic-Cenozoic oceans. Substantial differences emerged in the quality of algal biomass between the Palaeozoic and Mesozoic-Cenozoic growth regimes; these differences were strongly affected by interspecific interactions (i.e., the co-existence of different species alters responses to the chemistry of the medium). The change was in the direction of a Mesozoic-Cenozoic biomass enriched in protein per mole C, although cells contained less carbon overall. This would lead to a lower C:N ratio. On the assumption that Mesozoic-Cenozoic grazers' assimilation of total C was similar to that of their earlier counterparts, their diet would be stoichiometrically closer to their C:N requirement. This, along with an increase in mean cell size among continental shelf phytoplankton, could have helped to facilitate observed evolutionary changes in the Mesozoic marine fauna. In turn, increased grazing pressure would have operated as a selective force for the radiation of phytoplankton clades better equipped with antigrazing capabilities (sensu lato), as found widely in phytoplankton with biomineralization. Our results emphasize potential links between changing seawater chemistry, increased predation pressure and the rise to ecological dominance of chlorophyll a+c algae in Mesozoic oceans. The experiments also suggest a potential role for ocean chemistry in changes of marine trophic structure from the Palaeozoic to the later Mesozoic Era.
- MeSH
- biomasa * MeSH
- chlorofyl a metabolismus MeSH
- chlorofyl metabolismus MeSH
- fytoplankton metabolismus MeSH
- oceány a moře MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Geografické názvy
- oceány a moře MeSH
The diatom Phaeodactylum tricornutum was cultured in five different growth regimes to obtain cells with different composition. Pairs of populations subjected to different treatments were then mixed in a communal culture regime that differed from those of origin. After 6 h, the ratio between the two populations was verified by flow cytometry. Alterations in this ratio were found when cells previously grown at 1 mM NH4+ were mixed with GeO2 - and 0.5 mM NH4+ -grown cells. The nutritional background may thus make cells differently suited to new environmental conditions and afford advantages in terms of reproductive potential. Competitive interactions between populations may result from the differences in the expressed proteome and/or in the availability of tools for regulatory responses. This may have relevance to the persistence of phenotypically neutral variants present in the population best suited to the new condition, after the interaction of the conspecifics with different nutritional histories.
The assimilation of N-NO3- requires more energy than that of N-NH4+ . This becomes relevant when energy is limiting and may impinge differently on cell energy budget depending on depth, time of the day and season. We hypothesize that N-limited and energy-limited cells of the oceanic cyanobacterium Synechococcus sp. differ in their response to the N source with respect to growth, elemental stoichiometry and carbon allocation. Under N limitation, cells retained almost absolute homeostasis of elemental and organic composition, and the use of NH4+ did not stimulate growth. When energy was limiting, however, Synechococcus grew faster in NH4+ than in NO3- and had higher C (20%), N (38%) and S (30%) cell quotas. Furthermore, more C was allocated to protein, whereas the carbohydrate and lipid pool size did not change appreciably. Energy limitation also led to a higher photosynthetic rate relative to N limitation. We interpret these results as an indication that, under energy limitation, the use of the least expensive N source allowed a spillover of the energy saved from N assimilation to the assimilation of other nutrients. The change in elemental stoichiometry influenced C allocation, inducing an increase in cell protein, which resulted in a stimulation of photosynthesis and growth.
- MeSH
- adenosintrifosfát metabolismus MeSH
- amoniové sloučeniny farmakologie MeSH
- bakteriální proteiny metabolismus MeSH
- biomasa MeSH
- dusičnany farmakologie MeSH
- dusík metabolismus MeSH
- energetický metabolismus * účinky léků MeSH
- fosfor metabolismus MeSH
- fotosyntéza účinky léků MeSH
- kyslík metabolismus MeSH
- lipidy analýza MeSH
- sacharidy analýza MeSH
- síra metabolismus MeSH
- Synechococcus cytologie účinky léků růst a vývoj metabolismus MeSH
- uhlík metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
This work originates from three facts: (i) changes in CO2 availability influence metabolic processes in algal cells; (ii) Spatial and temporal variations of nitrogen availability cause repercussions on phytoplankton physiology; (iii) Growth and cell composition are dependent on the stoichiometry of nutritional resources. In this study, we assess whether the impact of rising pCO2 is influenced by N availability, through the impact that it would have on the C/N stoichiometry, in conditions of N sufficiency. Our experiments used the dinoflagellate Protoceratium reticulatum, which we cultured under three CO2 regimes (400, 1,000, and 5,000 ppmv, pH of 8.1) and either variable (the NO3(-) concentration was always 2.5 mmol · L(-1) ) or constant (NO3(-) concentration varied to maintain the same Ci /NO3(-) ratio at all pCO2 ) Ci /NO3(-) ratio. Regardless of N availability, cells had higher specific growth rates, but lower cell dry weight and C and N quotas, at elevated CO2 . The carbohydrate pool size and the C/N was unaltered in all treatments. The lipid content only decreased at high pCO2 at constant Ci /NO3(-) ratio. In the variable Ci /NO3(-) conditions, the relative abundance of Rubisco (and other proteins) also changed; this did not occur at constant Ci /NO3(-) . Thus, the biomass quality of P. reticulatum for grazers was affected by the Ci /NO3(-) ratio in the environment and not only by the pCO2 , both with respect to the size of the main organic pools and the composition of the expressed proteome.
The acquisition and assimilation of inorganic C have been investigated in several of the 15 clades of the Ochrophyta other than diatoms, with biochemical, physiological and genomic data indicating significant mechanistic variation. Form ID Rubiscos in the Ochrophyta are characterized by a broad range of kinetics values. In spite of relatively high K0.5CO2 and low CO2 : O2 selectivity, diffusive entry of CO2 occurs in the Chrysophyceae and Synurophyceae. Eustigmatophyceae and Phaeophyceae, on the contrary, have CO2 concentrating mechanisms, usually involving the direct or indirect use of [Formula: see text] This variability is possibly due to the ecological contexts of the organism. In brown algae, C fixation generally takes place through a classical C3 metabolism, but there are some hints of the occurrence of C4 metabolism and low amplitude CAM in a few members of the Fucales. Genomic data show the presence of a number of potential C4 and CAM genes in Ochrophyta other than diatoms, but the other core functions of many of these genes give a very limited diagnostic value to their presence and are insufficient to conclude that C4 photosynthesis is present in these algae.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'.
The carbon-concentrating mechanisms (CCMs) of cyanobacteria counteract the low CO2 affinity and CO2:O2 selectivities of the Rubisco of these photolithotrophs and the relatively low oceanic CO2 availability. CCMs have a significant energy cost; if light is limiting, the use of N sources whose assimilation demands less energy could permit a greater investment of energy into CCMs and inorganic C (Ci) assimilation. To test this, we cultured Synechococcus sp. UTEX LB 2380 under either N or energy limitation, in the presence of NO3- or NH4+. When growth was energy-limited, NH4+-grown cells had a 1.2-fold higher growth rate, 1.3-fold higher dissolved inorganic carbon (DIC)-saturated photosynthetic rate, 19% higher linear electron transfer, 80% higher photosynthetic 1/K1/2(DIC), 2.0-fold greater slope of the linear part of the photosynthesis versus DIC curve, 3.5-fold larger intracellular Ci pool, and 2.3-fold higher Zn quota than NO3--grown cells. When energy was not limiting growth, there were not differences between NH4+- and NO3--grown cells, except for higher linear electron transfer and larger intracellular Ci pool.We conclude that, when energy limits growth, cells that use the cheaper N source divert energy from N assimilation to C acquisition and assimilation; this does not happen when energy is not limiting.
