Variation In Species Research Articles

Evolution of the correlated genomic variation landscape across a divergence continuum in the genus Castanopsis.

The heterogeneous landscape of genomic variation has been well documented in population genomic studies. However, disentangling the intricate interplay of evolutionary forces influencing the genetic variation landscape over time remains challenging. In this study, we assembled a chromosome-level genome for Castanopsis eyrei and sequenced the whole genomes of 276 individuals from 12 Castanopsis species, spanning a broad divergence continuum. We found highly correlated genomic variation landscapes across these species. Furthermore, variations in genetic diversity and differentiation along the genome were strongly associated with recombination rates and gene density. These results suggest that long-term linked selection and conserved genomic features have contributed to the formation of a common genomic variation landscape. By examining how correlations between population summary statistics change throughout the species divergence continuum, we determined that background selection alone does not fully explain the observed patterns of genomic variation; the effects of recurrent selective sweeps must be considered. We further revealed that extensive gene flow has significantly influenced patterns of genomic variation in Castanopsis species. The estimated admixture proportion correlated positively with recombination rate and negatively with gene density, supporting a scenario of selection against gene flow. Additionally, putative introgression regions exhibited strong signals of positive selection, an enrichment of functional genes, and reduced genetic burdens, indicating that adaptive introgression has played a role in shaping the genomes of hybridizing species. This study provides insights into how different evolutionary forces have interacted in driving the evolution of the genomic variation landscape.

Benthic foraminifera biomass on the continental slope and São Paulo plateau of Santos Basin (SE Brazil): Comparison of different estimation methods

The biomass of benthic foraminifera stands out in marine environments compared to other meiofaunal organisms. Estimating the biomass of these organisms is a valuable biotic descriptor for understanding the carbon cycle and the flow of particulate organic matter. This study estimates the biomass of benthic foraminifera on the slope and plateau of the Santos Basin (SE Brazil) using the biovolume and cytoplasmic occupancy methodology. This work applies a non-destructive biovolume method of estimating biomass by the direct visualization of cytoplasmic occupancy (DV) compared with pre-established (in the literature) percentages of cytoplasmic occupation of the test volume: an average of 32 % (GE) and 35 % (AL). Although there was no statistically significant difference (p < 0.05) between DV and cytoplasmic percentages, it is recognized that the calculation of GE and AL can bias the results. We, therefore, emphasize the need to assess biomass according to species composition and ultrastructural variability. The species with the biggest individuals (>250 μm) contributed most to biomass in the Santos Basin and are considered k-strategists. In contrast, the species with smaller specimens (250–63 μm) are considered r-strategists, contributing more to the density in the study area. This study highlights the discrepancy between the abundant species biomass results by measuring all specimens and the extrapolation of the population for less sample effort, probably due to biological (e.g. intra/inter species variations) and environmental (e.g. availability of food and oxygen) factors. Based on the ecology of the species, the biomass estimates seem to reveal a relationship with the quantity and quality of organic matter, which will be investigated in the future. Future studies should consider the internal structures and address potential errors resulting from cytoplasm dehydration when staining and drying are performed.

HEMATOLOGY AND BIOCHEMISTRY REFERENCE VALUES IN NESTLING RED KITES (MILVUS MILVUS) IN SHORT-TERM HUMAN CARE IN ENGLAND.

Between the years 2022 and 2023, 62 red kite (Milvus milvus) nestlings were translocated from England to Spain to bolster declining populations in mainland Europe as part of a wider conservation initiative. Health examinations were undertaken by veterinarians ahead of translocation, including examination of hematology and biochemistry parameters from blood samples. This study aimed to establish reference values for these parameters in nestling red kites for use in future translocations or for other clinical purposes. All individuals included in the analysis were clinically healthy at the time of sampling. Biochemical reference intervals were comparable to published values for other Accipitridae, although differences in hematology were noted: PCV was generally lower; and WBC counts higher than (up to triple) those reported for related species of a similar age. It is hypothesized that these differences reflect species variations or the effects of the stress of recent capture on the immune system of the red kites. A Leucocytozoon species was identified on blood smears of six of the red kites. The reference intervals presented in this study are representative of free-living red kite nestlings in England that have recently been captured for conservation translocation purposes.

Elemental composition of post-wildfire biomass ashes and partly burned woody species in Bohemian Switzerland National Park, Czech Republic.

The study explored the post-wildfire elemental composition of parts (wood, bark, branch, cone, trunk, litter, twig, needle, sward, fallow, sapling, etc.) and by-products (biomass ashes, partly burnt parts, and char) of different woody species in the Bohemian Switzerland National Park, Czech Republic, and considered their effects on soils. Multi-elemental analysis of the fire by-products of the woody species was determined with inductively coupled plasma-optical emission spectrometry and mass spectrometry and compared with control biomass samples unaffected by wildfire. Most fire by-products were slightly alkaline, with acidic ashes obtained from blueberry wood. The by-products of the wildfire were characterized by varied total contents of macro (P, Ca, K, Mg, and S), micro (Na, Mn, Fe, Cu, and Zn), and other elements (B, Co, Mo, and V) vital to soil fertility and plant growth. The mean content of macro elements in the biomass ashes was up to 4.16 P, 23.5 Ca, 2.48Mg, 63K, and 5.57 S g kg-1. These values were comparatively lower than published data for ashes obtained under optimized conditions, e.g., those combusted in power generation facilities. Conversely, partly burnt parts-an indication of incomplete combustion-had higher 9.22 P, 79 Ca, and 5.99Mggkg-1 contents in spruce needles than in biomass ashes and the control. Variations in woody species and anthropogenic activities in areas of wildfires produced varied As, Cd, Cr, Ni, and Pb contents above EU fertilizer regulation. Caution in applying biomass ashes from wildfires on fields is required due to risk/toxic elements input from anthropogenic activities. Wildfire effects on the elemental composition of woody species can provide information on plant parts most suitable for biomass ashes for soil and ecosystem safety.

Molecular analysis of feces reveals gastrointestinal nematodes in reintroduced wild asses of the Negev desert

Reintroduced animals face disease risks, potentially impacting both the reintroduced and the local wildlife/domestic populations. This study focuses on the Asiatic wild asses (Equus hemionus) reintroduced to the Negev desert in southern Israel. Despite potential threats of disease spill-over to and from domesticated donkeys and horses in the area, there are no records of the gastrointestinal nematodes (GIN) of the wild ass population. We used DNA metabarcoding on fecal samples of wild asses collected across seasons and habitats, near water sources that they frequently use. Ten GIN species were detected in the feces, nine belonging to the family Strongylidae, which commonly infects and causes disease in equids worldwide, such as horses, zebras, and donkeys. Some of these Strongylidae species are also found in domesticated equids in Israel, thus raising concerns regarding potential parasite transmission between wild and domestic animals. The high prevalence of certain GIN species suggests frequent transmission, likely due to the congregation of the wild asses around water sources. While we observed statistically significant variations in some GIN species across seasons and habitats, we did not find clear overall differences between GIN communities. DNA metabarcoding proves to be a valuable tool for identifying GIN species in wild animals, with potential applications in monitoring their health and preventing disease transmission to and from domestic animals.

Variability of lead-zinc sulfide ore slurry rheological properties and its influence on flotation conditions

We investigated how the rheological characteristics of a flotation slurry change in response to variations in mineral species, slurry concentration, and particle size; slurry pH; and trap and rheological control reagent concentrations using slurries containing galena, sphalerite, quartz, and kaolinite. The results indicate that reducing particle size and increasing slurry concentration leads to varying degrees of increase in apparent viscosity and yield stress. At the same particle size, the slurry exhibits the following order of apparent viscosity and yield stress: kaolinite &gt; galena &gt; sphalerite &gt; quartz. In addition, as the slurry’s apparent viscosity and yield stress increase, the rheology decreases, creating progressively unfavorable conditions for the flotation of lead, zinc, and other target minerals. Furthermore, changes in pH have no significant effect on the slurry’s rheology when the slurry is comprised of vein minerals. Moreover, galena and sphalerite depict particle agglomeration in the slurry. Ultimately, the addition of sodium silicate as a rheological control reagent substantially enhances the slurry’s rheological properties. This results in a system where problematic minerals like kaolinite are more effectively dispersed, thereby promoting efficient lead-zinc mineral flotation. Regarding the flotation of lead sulfide and zinc minerals, the addition of kaolinite raises the apparent viscosity of the mixed slurry, hindering the flotation of the target minerals. Conversely, quartz lowers the apparent viscosity aiding the flotation separation process. Understanding the relationship between flotation conditions and the pulp’s rheological properties can provide valuable guidance for subsequent flotation tests.

Insertions and Deletions: Computational Methods, Evolutionary Dynamics, and Biological Applications.

Insertions and deletions constitute the second most important source of natural genomic variation. Insertions and deletions make up to 25% of genomic variants in humans and are involved in complex evolutionary processes including genomic rearrangements, adaptation, and speciation. Recent advances in long-read sequencing technologies allow detailed inference of insertions and deletion variation in species and populations. Yet, despite their importance, evolutionary studies have traditionally ignored or mishandled insertions and deletions due to a lack of comprehensive methodologies and statistical models of insertions and deletion dynamics. Here, we discuss methods for describing insertions and deletion variation and modeling insertions and deletions over evolutionary time. We provide practical advice for tackling insertions and deletions in genomic sequences and illustrate our discussion with examples of insertions and deletion-induced effects in human and other natural populations and their contribution to evolutionary processes. We outline promising directions for future developments in statistical methodologies that would allow researchers to analyze insertions and deletion variation and their effects in large genomic data sets and to incorporate insertions and deletions in evolutionary inference.

Variations of silicon species, dissolution and crystallinity within sichars prepared under different heating rate

Silicon within Si-rich biochars (sichar) plays a crucial role in immobilizing heavy metals and providing slow-releasing bioavailable silicon for silicophilic plants. However, the impact of heating rate on the silicon properties and carbon‑silicon interactions in sichars remains unclear. In this study, rice husk was used as a silicon-rich biomass to prepare sichars at different heating rates (10, 30 and 60 °C per minute, and ultra-fast-pyrolysis), then experiments such as silicon concentration measurement, Raman and XRD characterization were conducted. The results showed that a faster heating rate reduced the carbon content during pyrolysis while promoted the formation of amorphous silica, resulting in a threefold increase in dissolved silicon in sichars prepared at 400 °C. Additionally, we observed the formation of a meta-stable SiO2 polymorph (tridymite) in rice husk-derived biochars under fast heating, differing from the previously observed quartz generated at slow heating rates. Regarding the CSi relationship, a faster heating rate facilitated the removal of the surface carbon layer, exposing the underlying silicon layer. This led to more soluble silicon species and less encapsulated silicon, resulting in a continuous release and cumulative silicon dissolution amount 1.2 times and 1.6–1.9 times higher, respectively, than those in slow heating rate-derived sichars. Consequently, this enhanced silicon uptake in rice seedlings. Our findings indicate that beyond pyrolysis temperature, the heating rate significantly affects the silicon species, silicon dissolution behavior, and carbon‑silicon relationships of biochar, ultimately determines the properties and applications of sichars.

Specific leaf area and its within-individual variation in understory evergreen and deciduous woody species in New Zealand

Specific leaf area (SLA) plays a critical role in carbon assimilation and nutrient cycling. While leaf habit (deciduous vs. evergreen) has often been recognized as a reliable predictor of SLA—with deciduous species typically having higher mean SLA values due to lower concentration of structural components compared to evergreens—high variation in SLA among evergreen species suggests further investigation of variation for species with this leaf habit could improve predictions of SLA effects on community and ecosystem processes. Furthermore, the presence of leaves of different ages in evergreen plants, emerging over multiple years, could amplify the within-individual variation in SLA, which remains underexplored. Here we report variations of SLA measured from c. 2000 leaves collected from 36 individuals across 19 woody species in an understory environment in New Zealand (NZ). We found that while most deciduous species, predominantly non-native, clustered towards higher SLA values, evergreen species presented a wide SLA spectrum. Moreover, we found that while being deciduous, having a smaller leaf size, and younger leaves, collected from lateral branches, correlated with elevated SLA values, the leaf habit did not primarily drive the within-individual SLA variation. Instead, smaller leaf size emerged as a significant predictor of within-individual SLA variation. The branch-order effect on SLA underscores a methodological consideration: accurate estimation of total leaf area in evergreen trees requires representative sampling across all branch orders. Our study also highlights the need for integrating leaf traits such as leaf size and branch order into functional trait analyses. Further research is vital to understand the underlying mechanisms of these trait variations and their impacts on ecosystem functioning.

Phenotypic variability of Montastraea cavernosa and Porites astreoides along a depth gradient from shallow to mesophotic reefs in the Cayman Islands

Phenotypic variability is the ability of the same species to express different phenotypes under different environmental conditions. Several coral species that exist along a broad depth distribution have been shown to differ in skeletal morphology and nutrient acquisition at different depths, which has been attributed to variability in response to differing levels of light availability. This study examined the phenotypic variability of two common depth generalist corals, Montastraea cavernosa and Porites astreoides, along a gradient from 10 to 50 m in the Cayman Islands, by examining changes in skeletal morphology, photophysiology, symbiont cell density, and chlorophyll concentration. Skeletal features of M. cavernosa were found to increase in size from 10 to 30 m, but returned to smaller sizes from 30 to 50 m, while P. astreoides skeletal features continued to increase in size from 10 to 40 m. No differences were observed in either symbiont density or chlorophyll concentration across depths for either species. However, all photophysiological parameters exhibited significant depth-dependent variations in both species, revealing adaptive strategies to different light environments. These results suggest that both species have high variability in response to depth. Patterns of skeletal morphology and photophysiology, however, suggest that M. cavernosa may be more variable in regulating photosynthetic efficiency compared to P. astreoides, which likely facilitates the broader depth distribution of this species.

Existence of multiple transitions of the critical state due to anesthetics

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject.

A multi-peak performance landscape for scale biting in an adaptive radiation of pupfishes.

The physical interactions between organisms and their environment ultimately shape diversification rates, but the contributions of biomechanics to evolutionary divergence are frequently overlooked. Here, we estimated a performance landscape for biting in an adaptive radiation of Cyprinodon pupfishes, including scale-biting and molluscivore specialists, and compared performance peaks with previous estimates of the fitness landscape in this system. We used high-speed video to film feeding strikes on gelatin cubes by scale eater, molluscivore, generalist and hybrid pupfishes and measured bite dimensions. We then measured five kinematic variables from 227 strikes using the SLEAP machine-learning model. We found a complex performance landscape with two distinct peaks best predicted gel-biting performance, corresponding to a significant non-linear interaction between peak gape and peak jaw protrusion. Only scale eaters and their hybrids were able to perform strikes within the highest performance peak, characterized by larger peak gapes and greater jaw protrusion. A performance valley separated this peak from a lower performance peak accessible to all species, characterized by smaller peak gapes and less jaw protrusion. However, most individuals exhibited substantial variation in strike kinematics and species could not be reliably distinguished by their strikes, indicating many-to-many mapping of morphology to performance. The two performance peaks observed in the lab were partially consistent with estimates of a two-peak fitness landscape measured in the wild, with the exception of the new performance peak for scale eaters. We thus reveal a new bimodal non-linear biomechanical model that connects morphology to performance to fitness in a sympatric radiation of trophic niche specialists.

Leaf–Soil C:N:P Stoichiometry and Homeostasis Characteristics of Plantations in the Yellow River Floodplain in Western Shandong, China

The concentrations and ratios of plants C, N, and P serve as important indicators of ecological processes. However, how plant and soil C:N:P relationships and ratios change with forest stand types remain unclear. Here, we analyzed the ecological stoichiometric characteristics by measuring leaf and soil organic C, total N, and P contents in four stand types in Liaocheng, including Populus tomentosa Carrière pure forest, Populus tomentosa–Robinia pseudoacacia L. mixture forests, Platanus orientalis L. pure forest, and Salix matsudana Koidz. pure forests. We find that (1) The N and P leaf contents varied significantly across the four forest stands, with Populus tomentosa–Robinia pseudoacacia mixture forests having higher P levels. Platanus orientalis pure forests had lower C and N but higher P levels compared to others. (2) Uncoupled cycling of P in leaf–soil systems due to environmental influences, but C and N elements showed coupled cycles in some forest stands. (3) Populus tomentosa pure forests, Populus tomentosa–Robinia pseudoacacia mixture forests, Platanus orientalis pure forests are limited by N, and Salix matsudana pure forests are limited by both N and P elements. Overall, environmental factors, in addition to species variations, influence the C, N, P, and C:N:P ratios in leaves and soils of different forest stand types. Enhancing conservation and efficient use of N and P elements is crucial for sustainable plantation forest management to promote optimal growth in the region.

Temperature and biodiversity influence community stability differently in birds and fishes.

Determining the factors that affect community stability is crucial to understanding the maintenance of biodiversity and ecosystem functioning in the face of global warming. We investigated how four temperature components (that is, median, variability, trend and extremes) affected diversity-synchrony-stability relationships for 1,246 bird and 580 fish communities from temperate regions. We hypothesized a stabilizing effect on the community if the variation in species' response to changing median temperature decreases overall community synchrony (hypothesis H1) and if temperature extremes reduce interspecific synchrony at extreme abundances due to variation in species' thermal tolerance limits (hypothesis H2). We found support for H1 in fish and for H2 in bird communities. Here we showed that the abiotic components (that is, the median, variability, trend and extremes of temperature) had more indirect effects on community stability, predominantly by affecting the biotic components (that is, diversity, synchrony). Considering various temperature components' direct as well as indirect impacts on stability for terrestrial versus aquatic communities will improve our mechanistic understanding of biodiversity change in response to global climatic stressors.

Intraspecific trait variation of carrion beetle species and communities across elevations

Abstract Filtering processes across environmental gradients can structure patterns of trait variation within communities. The community‐weighted mean (CWM) is a metric that is commonly used to indicate the directionality of such filtering processes and the optimal adaptive strategy of taxa within community. Proximity to the CWM indicates higher fitness, and deviations from this optimal value result in changes in the relative abundances of coexisting species. We investigated patterns of intraspecific trait variation in four coexisting carrion beetle species (Coleoptera: Silphidae) across elevational gradients. The study was conducted in temperate forest ecosystems with distinct natural vegetation zones ranging from 950 m to 1700 m above sea level. Of the 12 traits measured, we found that intraspecific variation ranged from 34% (body length) to 100% (ratio of elytra length, head length and head width to body length) and accounted for a larger proportion of variation than interspecific variation in 7 traits. For most traits, trait range, which indicates the niche breadth of species at a given elevation, was positively correlated with relative abundance. The CWMs of traits associated with long‐distance dispersal decreased with elevation, whereas those associated with microhabitat use showed the opposite trend. Soil temperature influenced tibia length after controlling for the effects of species identity, but soil water content had no effect on trait variation. Patterns of variation in body width and thorax width of two beetle species supported the CWM‐optimality hypothesis; however, patterns of trait variation in body width and thorax length of another species showed an opposite trend. Our study identifies several traits that can be highly variable within carrion beetle species. Such high levels of intraspecific trait variation may enable populations to adapt across a wide range of elevations and vegetation types.

Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports.

This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease.

Mangiferin alleviates cisplatin-induced ototoxicity in sensorineural hearing loss

Mangiferin(MGF) exhibits crucial biological roles, including antioxidant and anti-inflammatory functions. However, how to clearly elucidate the functioning mechanism of MGF for inhibiting cisplatin-induced hearing loss requires in-depth investigation. In this work, we aimed at gaining insight into how MGF functions as the protective agent against cisplatin-triggered ototoxicity using various assays. The variation for reactive oxygen species (ROS) concentrations was determined with MitoSOX-Red and 2′,7′-Dichlorodihydrofluorescein diacetate staining (DCFH-DA). The protective function and corresponding mechanism of MGF in hair cell survival in the House Ear Institute-Organ of Corti (HEI-OC1) cell line were assessed using RNA sequencing (RNA-Seq). Our findings demonstrated that MGF significantly alleviated cisplatin-induced injury to hair cells in vitro, encompassing cell lines and cochlear explants, as well as in vivo models, including C57BL/6 J mice and zebrafish larvae. Mechanistic studies revealed that MGF reversed the increased accumulation of ROS and inhibited cell apoptosis through mitochondrial-mediated intrinsic pathway. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting data indicated MGF protected against cisplatin-mediated ototoxicity via the mitogen-activated protein kinase pathway (MAPK). These findings demonstrated MGF has significant potential promise in combating cisplatin-induced ototoxicity, offering a foundation for expanded investigation into therapeutic approaches for auditory protection.

Plasticity drives the trait variation of a foundation marsh species migrating into coastal forests with sea‐level rise

AbstractClimate‐driven ecosystem shifts occur through turnover in the foundation species which structure the landscape. Therefore, to predict the fate of areas undergoing climate‐driven ecosystem shifts, one approach is to characterize ecological and evolutionary responses of foundation species along dynamic environmental gradients. One such gradient is the ecotone between tidal marshes and maritime forests in coastal areas of the US Mid‐Atlantic region where accelerated sea‐level rise and coastal storms of increased frequency and intensity are driving forest dieback and inland marsh migration. Mid‐Atlantic tidal marshes are structured by marsh grasses which act as foundation species, and these grasses exhibit trait variation across their distribution from established marsh interior to their inland migration front. We conducted a reciprocal transplant experiment with Spartina patens, a dominant high marsh grass and foundation species, between established populations in the high marsh and range edge populations in the forest understory at three Mid‐Atlantic sites. We monitored environmental conditions in marsh and forest understory habitats, measured plant traits (above‐ and belowground biomass, specific leaf area, leaf N and C concentrations) in transplanted and reference non‐transplanted individuals, and used microsatellite markers to determine the genetic identity of transplants to quantify clonality between habitats and sites. Individuals transplanted into the forest understory exhibited a plastic shift in resource allocation to aboveground structures associated with light acquisition, with shifts in transplants making them more morphologically similar to reference individuals sampled from the forest habitat. Clonal diversity and genetic distance among transplants were relatively high at two of three sites, but individuals at all sites exhibited trans‐habitat plasticity regardless of clonal diversity or a lack thereof. Individuals grown in the forest understory showed lower vegetative and reproductive fitness. Nevertheless, the trait plasticity exhibited by this species allowed individuals from the forest that were transplanted into the marsh to recoup significant biomass in only a single growing season. We predict high plasticity will facilitate the persistence of colonizing S. patens individuals under suboptimal forest shade conditions until forest dieback increases light availability, ultimately promoting continued inland migration of this foundation species under sea‐level rise.

Redox heterogeneity in mouse embryonic stem cells individualizes cell fate decisions

Pluripotent embryonic stem cells (ESCs) can develop into any cell type in the body. Yet, the regulatory mechanisms that govern cell fate decisions during embryogenesis remain largely unknown. We now demonstrate that mouse ESCs (mESCs) display large natural variations in mitochondrial reactive oxygen species (mitoROS) levels that individualize their nuclear redox state, H3K4me3 landscape, and cell fate. While mESCs with high mitoROS levels (mitoROSHIGH) differentiate toward mesendoderm and form the primitive streak during gastrulation, mESCs, which generate less ROS, choose the alternative neuroectodermal fate. Temporal studies demonstrated that mesendodermal (ME) specification of mitoROSHIGH mESCs is mediated by a Nrf2-controlled switch in the nuclear redox state, triggered by the accumulation of redox-sensitive H3K4me3 marks, and executed by a hitherto unknown ROS-dependent activation process of the Wnt signaling pathway. In summary, our study explains how ESC heterogeneity is generated and used by individual cells to decide between distinct cellular fates.

Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease.

Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD. We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT. Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and -.233, p < .05), insulin (r = .327 and -.236, p < .05) and c-peptide (r = .318 and -.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity. This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.