Heritability has traditionally been thought to be a characteristic feature of the genetic material of an organism—notably, its DNA. However, it is now clear that inheritance not based on DNA sequence ...exists in multiple organisms, with examples found in microbes, plants, and invertebrate and vertebrate animals. In mammals, the molecular mechanisms have been challenging to elucidate, in part due to difficulties in designing robust models and approaches. Here we review some of the evidence, concepts, and potential mechanisms of non-DNA sequence-based transgenerational inheritance. We highlight model systems and discuss whether phenotypes are replicated or reconstructed over successive generations, as well as whether mechanisms operate at transcriptional and/or posttranscriptional levels. Finally, we explore the short- and long-term implications of non-DNA sequence-based inheritance. Understanding the effects of non-DNA sequence-based mechanisms is key to a full appreciation of heritability in health and disease.
Cytosine methylation is an ancient epigenetic modification yet its function and extent within genomes is highly variable across eukaryotes. In mammals, methylation controls transposable elements and ...regulates the promoters of genes. In insects, DNA methylation is generally restricted to a small subset of transcribed genes, with both intergenic regions and transposable elements (TEs) depleted of methylation. The evolutionary origin and the function of these methylation patterns are poorly understood. Here we characterise the evolution of DNA methylation across the arthropod phylum. While the common ancestor of the arthropods had low levels of TE methylation and did not methylate promoters, both of these functions have evolved independently in centipedes and mealybugs. In contrast, methylation of the exons of a subset of transcribed genes is ancestral and widely conserved across the phylum, but has been lost in specific lineages. A similar set of genes is methylated in all species that retained exon-enriched methylation. We show that these genes have characteristic patterns of expression correlating to broad transcription initiation sites and well-positioned nucleosomes, providing new insights into potential mechanisms driving methylation patterns over hundreds of millions of years.
Significance Autism spectrum disorder (ASD), encompassing impaired communication and social interaction, and repetitive stereotypic behavior and language, affects 1–2% of predominantly male ...individuals and is an enormous medical and economic problem for which there is no documented, mechanism-based treatment. In a placebo-controlled, randomized, double-blind clinical trial, daily oral administration for 18 wk of the phytochemical sulforaphane (derived from broccoli sprouts) to 29 young men with ASD substantially (and reversibly) improved behavior compared with 15 placebo recipients. Behavior was quantified by both parents/caregivers and physicians by three widely accepted measures. Sulforaphane, which showed negligible toxicity, was selected because it upregulates genes that protect aerobic cells against oxidative stress, inflammation, and DNA-damage, all of which are prominent and possibly mechanistic characteristics of ASD.
Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13–27) with moderate to severe ASD received the phytochemical sulforaphane ( n = 29)—derived from broccoli sprout extracts—or indistinguishable placebo ( n = 15). The effects on behavior of daily oral doses of sulforaphane (50–150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC ( P < 0.001, comparing treatments) and 17% for SRS scores ( P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication ( P = 0.015–0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.
Understanding strongly correlated phases of matter, such as the quark-gluon plasma and neutron stars, and in particular the dynamics of such systems, for example, following a Hamiltonian quench (a ...sudden change in some Hamiltonian parameter, such as the strength of interparticle interactions) is a fundamental challenge in modern physics. Ultracold atomic gases are excellent quantum simulators for these problems, owing to their tunable interparticle interactions and experimentally resolvable intrinsic timescales. In particular, they provide access to the unitary regime, in which the interactions are as strong as allowed by quantum mechanics. This regime has been extensively studied in Fermi gases
. The less-explored unitary Bose gases
offer possibilities
such as universal physics controlled solely by the gas density
and new forms of superfluidity
. Here, through momentum- and time-resolved studies, we explore degenerate and thermal homogeneous Bose gases quenched to unitarity. In degenerate samples, we observe universal post-quench dynamics in agreement with the emergence of a prethermal state
with a universal non-zero condensed fraction
. In thermal gases, the dynamic and thermodynamic properties generally depend on the gas density and the temperature, but we find that they can still be expressed in terms of universal dimensionless functions. Surprisingly, we find that the total quench-induced correlation energy is independent of the gas temperature. These measurements provide quantitative benchmarks and challenges for the theory of unitary Bose gases.
IMPORTANCE: While air pollutants at historical levels have been associated with cardiovascular and respiratory diseases, it is not known whether exposure to contemporary air pollutant concentrations ...is associated with progression of emphysema. OBJECTIVE: To assess the longitudinal association of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon exposure with change in percent emphysema assessed via computed tomographic (CT) imaging and lung function. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Air and Lung Studies conducted in 6 metropolitan regions of the United States, which included 6814 adults aged 45 to 84 years recruited between July 2000 and August 2002, and an additional 257 participants recruited from February 2005 to May 2007, with follow-up through November 2018. EXPOSURES: Residence-specific air pollutant concentrations (O3, PM2.5, NOx, and black carbon) were estimated by validated spatiotemporal models incorporating cohort-specific monitoring, determined from 1999 through the end of follow-up. MAIN OUTCOMES AND MEASURES: Percent emphysema, defined as the percent of lung pixels less than −950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scans (2010-2018). Spirometry was performed up to 3 times per participant (2004-2018). RESULTS: Among 7071 study participants (mean range age at recruitment, 60 45-84 years; 3330 47.1% were men), 5780 were assigned outdoor residential air pollution concentrations in the year of their baseline examination and during the follow-up period and had at least 1 follow-up CT scan, and 2772 had at least 1 follow-up spirometric assessment, over a median of 10 years. Median percent emphysema was 3% at baseline and increased a mean of 0.58 percentage points per 10 years. Mean ambient concentrations of PM2.5 and NOx, but not O3, decreased substantially during follow-up. Ambient concentrations of O3, PM2.5, NOx, and black carbon at study baseline were significantly associated with greater increases in percent emphysema per 10 years (O3: 0.13 per 3 parts per billion 95% CI, 0.03-0.24; PM2.5: 0.11 per 2 μg/m3 95% CI, 0.03-0.19; NOx: 0.06 per 10 parts per billion 95% CI, 0.01-0.12; black carbon: 0.10 per 0.2 μg/m3 95% CI, 0.01-0.18). Ambient O3 and NOx concentrations, but not PM2.5 concentrations, during follow-up were also significantly associated with greater increases in percent emphysema. Ambient O3 concentrations, but not other pollutants, at baseline and during follow-up were significantly associated with a greater decline in forced expiratory volume in 1 second per 10 years (baseline: 13.41 mL per 3 parts per billion 95% CI, 0.7-26.1; follow-up: 18.15 mL per 3 parts per billion 95% CI, 1.59-34.71). CONCLUSIONS AND RELEVANCE: In this cohort study conducted between 2000 and 2018 in 6 US metropolitan regions, long-term exposure to ambient air pollutants was significantly associated with increasing emphysema assessed quantitatively using CT imaging and lung function.
Dynamics of dissolved organic matter (DOM) in ecosystems are controlled by a suite of interacting physical, chemical, and biological factors. Growing recognition of the associations between microbial ...communities and metabolism and intrinsic DOM characteristics, highlight the potential importance of microbe-DOM relationships to modulate the role and fate of DOM, yet these relationships are difficult to isolate because they often operate across confounding environmental gradients. In a controlled laboratory incubation (44 days), we integrated DOM bulk and molecular characterization, bacterial abundances, microbial assemblage composition, nutrient concentrations, and cellular respiration to discern the structural dynamics of biological processing among DOM sources from different allochthonous litters (grass, deciduous leaves, and evergreen needles). We identified two periods, consistent among DOM sources, where processing dynamics differed. Further, bulk fluorescent analyses showed shifts from low to high excitation and emission wavelengths, indicating the biological production of more complex/degraded materials over time. Molecular level analyses revealed similar temporal patterns among DOM sources in the production and consumption of individual chemical components varying in reactivity and heteroatomic content. Despite these similarities, total carbon (C) removed and carbon dioxide (CO₂) accumulation differed by ~ 20% and 25% among DOM sources. This range in C processing was apparently tied to key chemical properties of the DOM (e.g., initial DOM composition, N content, and labile nature) as well as differential reorganization of the microbial populations that decomposed the DOM. We conclude that the production, transformation, and consumption of C in aquatic ecosystems is strongly dependent on the source and character of DOM as well as the structure of the microbial communities present, both of which change as DOM is processed over time. It is crucial that stream C processing models represent this complexity accurately.
Fungal pathogens, among other stressors, negatively impact the productivity and population size of honey bees, one of our most important pollinators (1, 2), in particular their brood (larvae and ...pupae) (3, 4). Understanding the factors that influence disease incidence and prevalence in brood may help us improve colony health and productivity. Here, we examined the capacity of a honey bee-associated bacterium, Bombella apis, to suppress the growth of fungal pathogens and ultimately protect bee brood from infection. Our results showed that strains of
inhibit the growth of two insect fungal pathogens, Beauveria bassiana and Aspergillus flavus,
. This phenotype was recapitulated
; bee broods supplemented with
were significantly less likely to be infected by A. flavus. Additionally, the presence of
reduced sporulation of A. flavus in the few bees that were infected. Analyses of biosynthetic gene clusters across
strains suggest antifungal candidates, including a type 1 polyketide, terpene, and aryl polyene. Secreted metabolites from
alone were sufficient to suppress fungal growth, supporting the hypothesis that fungal inhibition is mediated by an antifungal metabolite. Together, these data suggest that
can suppress fungal infections in bee brood via secretion of an antifungal metabolite.
Fungi can play critical roles in host microbiomes (5-7), yet bacterial-fungal interactions are understudied. For insects, fungi are the leading cause of disease (5, 8). In particular, populations of the European honey bee (Apis mellifera), an agriculturally and economically critical species, have declined in part due to fungal pathogens. The presence and prevalence of fungal pathogens in honey bees have far-reaching consequences, endangering other species and threatening food security (1, 2, 9). Our research highlights how a bacterial symbiont protects bee brood from fungal infection. Further mechanistic work could lead to the development of new antifungal treatments.
This paper represents a DNA barcode data release for 3,400 specimens representing 521 species of fishes from 6 areas across the Caribbean and western central Atlantic regions (FAO Region 31). Merged ...with our prior published data, the combined efforts result in 3,964 specimens representing 572 species of marine fishes and constitute one of the most comprehensive DNA barcoding "coverages" for a region reported to date. The barcode data are providing new insights into Caribbean shorefish diversity, allowing for more and more accurate DNA-based identifications of larvae, juveniles, and unknown specimens. Examples are given correcting previous work that was erroneous due to database incompleteness.
Microbes influence soil organic matter decomposition and the long‐term stabilization of carbon (C) in soils. We contend that by revising the representation of microbial processes and their ...interactions with the physicochemical soil environment, Earth system models (ESMs) will make more realistic global C cycle projections. Explicit representation of microbial processes presents considerable challenges due to the scale at which these processes occur. Thus, applying microbial theory in ESMs requires a framework to link micro‐scale process‐level understanding and measurements to macro‐scale models used to make decadal‐ to century‐long projections. Here we review the diversity, advantages, and pitfalls of simulating soil biogeochemical cycles using microbial‐explicit modeling approaches. We present a roadmap for how to begin building, applying, and evaluating reliable microbial‐explicit model formulations that can be applied in ESMs. Drawing from experience with traditional decomposition models, we suggest the following: (1) guidelines for common model parameters and output that can facilitate future model intercomparisons; (2) development of benchmarking and model‐data integration frameworks that can be used to effectively guide, inform, and evaluate model parameterizations with data from well‐curated repositories; and (3) the application of scaling methods to integrate microbial‐explicit soil biogeochemistry modules within ESMs. With contributions across scientific disciplines, we feel this roadmap can advance our fundamental understanding of soil biogeochemical dynamics and more realistically project likely soil C response to environmental change at global scales.
Key Points
Microbial‐explicit models differ in predictions from conventional models
Applying microbial‐explicit models may improve global C cycle projections
Spanning microbial to global scales requires integrative model‐data approaches
Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive ...clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.
An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration.
We derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema.
QCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.
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