Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid ...metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL) and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency.
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•ACSS2 is upregulated upon genetic deletion of Acly in vitro and in vivo•Acetate sustains viability in Acly-deficient MEFs, but proliferation is impaired•Low levels of acetate can supply abundant acetyl-CoA in the absence of ACLY•Acetate partially rescues lipogenesis and histone acetylation in ACLY deficiency
Zhao et al. demonstrate that ACLY deficiency causes upregulation of ACSS2 in proliferating cells in vitro and adipocytes in vivo. Acetate is needed for viability and is used for lipid synthesis and histone acetylation in the absence of ACLY. Proliferation is constrained in ACLY-deficient cells, despite ACSS2 compensation.
This review synthesizes evidence that altered fire frequency drives discontinuous ecosystem transitions from mesic grasslands to shrublands or woodlands in the Central Great Plains, USA. Long‐term ...fire manipulations reveal that grassland to shrubland transitions are triggered when fire‐free intervals increase from 1–3 years to ≥ 3–8 years, and longer fire returns (˜10 years or more) result in transitions to woodlands. Grazing and soil properties alter these fire thresholds. Grassland to shrubland transitions are abrupt and exhibit nonlinear relationships between driver and state variables. Transitions to shrublands and woodlands exhibit hysteresis, where reintroducing frequent fires does not reverse transitions in management‐relevant time‐scales (decades). Nonlinear transitions and hysteresis emerge because grasses generate positive feedbacks with fire that create strong demographic barriers for shrub and tree establishment. Fire‐free intervals allow shrubs and trees to reach a size sufficient to survive fire, reproduce and disrupt the fire feedback loop through competition. Synthesis. Mesic grasslands, shrublands and woodlands constitute self‐reinforcing states (alternative attractors) separated by critical fire frequency thresholds. Even without major shifts in climate, altered fire frequency can produce dramatic state changes, highlighting the importance of fire for predicting future ecosystem states. Local management should focus on prevention of unwanted transitions rather than post hoc restoration.
Hysteresis is a fundamental characteristic of alternative stable state theory, yet evidence of hysteresis is rare. In mesic grasslands, fire frequency regulates transition from grass‐ to ...shrub‐dominated system states. It is uncertain, however, if increasing fire frequency can reverse shrub expansion, or if grass‐shrub dynamics exhibit hysteresis. We implemented annual burning in two infrequently burned grasslands and ceased burning in two grasslands burned annually. With annual fires, grassland composition converged on that of long‐term annually burned vegetation due to rapid recovery of grass cover, although shrubs persisted. When annual burning ceased, shrub cover increased, but community composition did not converge with a long‐term infrequently burned reference site because of stochastic and lagged dispersal by shrubs, reflecting hysteresis. Our results demonstrated that annual burning can slow, but not reverse, shrub encroachment. In addition, reversing fire frequencies resulted in hysteresis because vegetation trajectories from grassland to shrubland differed from those of shrubland to grassland.
Hysteresis is a key characteristic of alternative stable state theory, yet evidence of hysteresis is rare. We implemented annual burning in two infrequently burned grasslands and ceased burning in two grasslands burned annually to test for hysteresis. Reversing fire frequencies in this 25–40 year long experiment resulted in hysteresis because vegetation trajectories from grassland to shrubland differed from those of shrubland to grassland.
•Callous-unemotional (CU) traits represent the affective features of psychopathy.•The heritability of CU traits likely lies between 36–67%.•Candidate gene studies implicate the serotonin and oxytocin ...systems in CU traits.•Epigenetic changes to serotonin and oxytocin genes are associated with CU traits.•No genome-wide loci for CU traits have yet been reported.
Callous-unemotional (CU) traits represent the affective features of psychopathy used to delineate youth at high risk for externalizing pathology. The genetic etiology CU traits is not currently well-understood.
The current review surveyed the literature for studies on the genetic underpinnings of CU traits and integrated information from 39 genetic studies.
The results from 24 studies with quantitative data suggest that the heritability for CU traits is likely between 36–67%. A majority of the 16 molecular genetic studies focused on candidate genes in the serotonin and oxytocin systems with results that have not been well replicated. Although two genome-wide association studies have been conducted, no genome-wide significant loci have been discovered.
There is some evidence to suggest that the serotonin and oxytocin systems may play a role in CU traits; however, there is currently not enough evidence to implicate specific genetic mechanisms. The authors encourage researchers to continue to apply the most up-to-date and relevant methodology, specifically collaborations and consortiums using genome-wide and polygenic methods.
Species diversity has declined in ecosystems worldwide as a result of habitat fragmentation, eutrophication, and land-use change. If such decline is to be halted ecological mechanisms that restore or ...maintain biodiversity are needed. Two long-term field experiments were performed in native grassland to assess the effects of fire, nitrogen addition, and grazing or mowing on plant species diversity. In one experiment, richness declined on burned and fertilized treatments, whereas mowing maintained diversity under these conditions. In the second experiment, loss of species diversity due to frequent burning was reversed by bison, a keystone herbivore in North American grasslands. Thus, mowing or the reestablishment of grazing in anthropogenically stressed grasslands enhanced biodiversity
Climate variability and periodic droughts have complex effects on carbon (C) fluxes, with uncertain implications for ecosystem C balance under a changing climate. Responses to climate change can be ...modulated by persistent effects of climate history on plant communities, soil microbial activity, and nutrient cycling (i.e., legacies). To assess how legacies of past precipitation regimes influence tallgrass prairie C cycling under new precipitation regimes, we modified a long‐term irrigation experiment that simulated a wetter climate for >25 years. We reversed irrigated and control (ambient precipitation) treatments in some plots and imposed an experimental drought in plots with a history of irrigation or ambient precipitation to assess how climate legacies affect aboveground net primary productivity (ANPP), soil respiration, and selected soil C pools. Legacy effects of elevated precipitation (irrigation) included higher C fluxes and altered labile soil C pools, and in some cases altered sensitivity to new climate treatments. Indeed, decades of irrigation reduced the sensitivity of both ANPP and soil respiration to drought compared with controls. Positive legacy effects of irrigation on ANPP persisted for at least 3 years following treatment reversal, were apparent in both wet and dry years, and were associated with altered plant functional composition. In contrast, legacy effects on soil respiration were comparatively short‐lived and did not manifest under natural or experimentally‐imposed “wet years,” suggesting that legacy effects on CO2 efflux are contingent on current conditions. Although total soil C remained similar across treatments, long‐term irrigation increased labile soil C and the sensitivity of microbial biomass C to drought. Importantly, the magnitude of legacy effects for all response variables varied with topography, suggesting that landscape can modulate the strength and direction of climate legacies. Our results demonstrate the role of climate history as an important determinant of terrestrial C cycling responses to future climate changes.
Historic precipitation manipulations in tallgrass prairie resulted in multi‐year carbon cycling legacy effects. Our study suggests that the sensitivity of carbon fluxes to climate perturbations can be shaped by previous climate patterns.
Sudden infant death syndrome (SIDS) is a leading cause of postneonatal infant mortality. Our previous meta-analyses showed that any breastfeeding is protective against SIDS with exclusive ...breastfeeding conferring a stronger effect.The duration of breastfeeding required to confer a protective effect is unknown.
To assess the associations between breastfeeding duration and SIDS.
Individual-level data from 8 case-control studies.
Case-control SIDS studies with breastfeeding data.
Breastfeeding variables, demographic factors, and other potential confounders were identified. Individual-study and pooled analyses were performed.
A total of 2267 SIDS cases and 6837 control infants were included. In multivariable pooled analysis, breastfeeding for <2 months was not protective (adjusted odds ratio aOR: 0.91, 95% confidence interval CI: 0.68-1.22). Any breastfeeding ≥2 months was protective, with greater protection seen with increased duration (2-4 months: aOR: 0.60, 95% CI: 0.44-0.82; 4-6 months: aOR: 0.40, 95% CI: 0.26-0.63; and >6 months: aOR: 0.36, 95% CI: 0.22-0.61). Although exclusive breastfeeding for <2 months was not protective (aOR: 0.82, 95% CI: 0.59-1.14), longer periods were protective (2-4 months: aOR: 0.61, 95% CI: 0.42-0.87; 4-6 months: aOR: 0.46, 95% CI: 0.29-0.74).
The variables collected in each study varied slightly, limiting our ability to include all studies in the analysis and control for all confounders.
Breastfeeding duration of at least 2 months was associated with half the risk of SIDS. Breastfeeding does not need to be exclusive to confer this protection.
U–Th–Pb zircon geochronology is an essential tool for quantifying the emplacement, differentiation and thermal evolution of crustal magmatic systems. However, the power of U–Pb zircon dates can be ...enhanced through complementary characterization of mineral texture and geochemistry, as this permits more detailed interpretations of geochronological datasets than conventionally achieved. Our approach to better relating zircon dates and geological processes consists of a multi-method analytical workflow, including cathodoluminescence imaging (CL), in situ LA-ICPMS/EPMA zircon geochemistry, U–Pb zircon ID-TIMS geochronology, and solution ICPMS zircon Trace Element Analysis (U–Pb TIMS-TEA). These methods are here applied to zircon from the Bergell Intrusion, a composite Alpine pluton preserving a ~10km mid-crustal transect. Hand samples of tonalite, granodiorite and hybridized granitoid each record 250–700kyr of autocrystic zircon growth. Bergell zircons are ubiquitously zoned with ca. 104–106yr growth histories, as evidenced by ID-TIMS analysis of microsampled fragments from single crystals. U–Pb TIMS-TEA data exhibit compositional trends on multiple spatiotemporal scales, including the handsample-scale, representing in situ differentiation at the emplacement level (e.g., Th/U); lithology-scale, defining trajectories corresponding to the production of tonalitic versus granodioritic magmas (Lu/Hf); and pluton-scale, indicating increasingly-evolved melts over ~1.6Myr of pluton assembly (Zr/Hf). These absolute TIMS-TEA temporal trends are corroborated by relative LA-ICPMS/EPMA core-to-rim geochemistry. We compare records of trace element evolution from TIMS-TEA, Bergell whole-rock geochemistry, and a global compilation of whole-rock geochemical data. These findings support zircon compositional evolution as a robust indicator of differentiation at local and crustal scales, and provide key empirical constraints on melt differentiation and cooling timescales in the middle crust.
•Introduction of zircon workflow, including LA-ICPMS transects, ID-TIMS geochronology, and solution ICPMS geochemistry.•Resolution of 104–106yr timescales of single zircon U–Pb age heterogeneity in mid-crustal plutonic rocks by ID-TIMS.•Temporal trends in zircon geochemistry are consistent with handsample-, lithology-, and pluton-scale differentiation.•Zircon growth histories permit determination of ~100–1000°C/Myr cooling rates in the middle to lower crust.
Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly ...understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high-fat diet (HFD) results in suppression of ATP citrate-lyase levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown. Here we examined the effects of HFD on levels of acyl-CoAs and histone acetylation in mouse white adipose tissue (WAT), liver, and pancreas. We report that mice consuming a HFD have reduced levels of acetyl-CoA and/or acetyl-CoA:CoA ratio in these tissues. In WAT and the pancreas, HFD also impacted the levels of histone acetylation; in particular, histone H3 lysine 23 acetylation was lower in HFD-fed mice. Genetic deletion of
in cultured adipocytes also suppressed acetyl-CoA and histone acetylation levels. In the liver, no significant effects on histone acetylation were observed with a HFD despite lower acetyl-CoA levels. Intriguingly, acetylation of several histone lysines correlated with the acetyl-CoA: (iso)butyryl-CoA ratio in liver. Butyryl-CoA and isobutyryl-CoA interacted with the acetyltransferase P300/CBP-associated factor (PCAF) in liver lysates and inhibited its activity
This study thus provides evidence that diet can impact tissue acyl-CoA and histone acetylation levels and that acetyl-CoA abundance correlates with acetylation of specific histone lysines in WAT but not in the liver.
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