Characterization of genome-wide H3K27ac profiles reveals a distinct PM2.5-associated histone modification signature

Complete list of differentially modified H3K27ac loci. (XLSX 69 kb

Singlino-driven Electroweak Baryogenesis in the Next-to-MSSM

We explore a new possibility of electroweak baryogenesis in the next-to-minimal supersymmetric standard model. In this model, a strong first-order electroweak phase transition can be achieved due to the additional singlet Higgs field. The new impact of its superpartner (singlino) on the baryon asymmetry is investigated by employing the closed-time-path formalism. We find that the CP violating source term fueled by the singlino could be large enough to generate the observed baryon asymmetry of the Universe without any conflicts with the current constraints from the non-observation of the Thallium, neutron and Mercury electric dipole moments.Comment: 11 pages, 2 figures. To appear in PL

Relative contributions of six lifestyle- and health-related exposures to epigenetic aging: The Coronary Artery Risk Development in Young Adults (CARDIA) study

BACKGROUND: DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavioral exposures, it is important to identify which of these exposures may have the strongest contributions to differences in GrimAA, to help guide potential intervention strategies. Here, we assessed the relative contributions of lifestyle- and health-related components, as well as their collective association, to GrimAA. RESULTS: We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with blood DNA methylation information at CARDIA Exam Year (Y) 20 (2005-2006, mean age 45.9 years). Six cumulative exposures by Y20 were included in the analysis: total packs of cigarettes, total alcohol consumption, education years, healthy diet score, sleep hours, and physical activity. We used quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods to assess the relative contribution of each exposure to a single overall association with GrimAA. We also assessed the collective association of the six components combined with GrimAA. Smoking showed the greatest positive contribution to GrimAA, accounting for 83.5% of overall positive associations of the six exposures with GrimAA (QGC weight = 0.835). The posterior inclusion probability (PIP) of smoking also achieved the highest score of 1.0 from BKMR analysis. Healthy diet and education years showed inverse contributions to GrimAA. We observed a U-shaped pattern in the contribution of alcohol consumption to GrimAA. While smoking was the greatest contributor across sex and race subgroups, the relative contributions of other components varied by subgroups. CONCLUSIONS: Smoking, alcohol consumption, and education showed the highest contributions to GrimAA in our study. Higher amounts of smoking and alcohol consumption were likely to contribute to greater GrimAA, whereas achieved education was likely to contribute to lower GrimAA. Identifying pertinent lifestyle- and health-related exposures in a context of collective components can provide direction for intervention strategies and suggests which components should be the primary focus for promoting younger GrimAA

The bacterium Pseudomonas protegens antagonizes the microalga Chlamydomonas reinhardtii using a blend of toxins

The unicellular alga Chlamydomonas reinhardtii and the bacterium Pseudomonas protegens serve as a model to study the interactions between photosynthetic and heterotrophic microorganisms. P . protegens secretes the cyclic lipopeptide orfamide A that interferes with cytosolic Ca 2+ homeostasis in C . reinhardtii resulting in deflagellation of the algal cells. Here, we studied the roles of additional secondary metabolites secreted by P . protegens using individual compounds and co‐cultivation of algae with bacterial mutants. Rhizoxin S2, pyrrolnitrin, pyoluteorin, 2,4‐diacetylphloroglucinol (DAPG) and orfamide A all induce changes in cell morphology and inhibit the growth of C . reinhardtii . Rhizoxin S2 exerts the strongest growth inhibition, and its action depends on the spatial structure of the environment (agar versus liquid culture). Algal motility is unaffected by rhizoxin S2 and is most potently inhibited by orfamide A (IC 50 = 4.1 μM). Pyrrolnitrin and pyoluteorin both interfere with algal cytosolic Ca 2+ homeostasis and motility whereas high concentrations of DAPG immobilize C . reinhardtii without deflagellation or disturbance of Ca 2+ homeostasis. Co‐cultivation with a regulatory mutant of bacterial secondary metabolism (Δ gacA ) promotes algal growth under spatially structured conditions. Our results reveal how a single soil bacterium uses an arsenal of secreted antialgal compounds with complementary and partially overlapping activities

Marijuana use and DNA methylation-based biological age in young adults

BACKGROUND: Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana\u27s effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation. RESULTS: A random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with available whole blood at examination years (Y) 15 and Y20 underwent epigenomic profiling. Four EAA estimates (intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration) were calculated from DNA methylation levels measured at Y15 and Y20. Ever use and cumulative marijuana-years were calculated from the baseline visit to Y15 and Y20, and recent marijuana use (both any and number of days of use in the last 30 days) were calculated at Y15 and Y20. Ever use of marijuana and each additional marijuana-year were associated with a 6-month (P \u3c 0.001) and a 2.5-month (P \u3c 0.001) higher average in GrimAge acceleration (GAA) using generalized estimating equations, respectively. Recent use and each additional day of recent use were associated with a 20-month (P \u3c 0.001) and a 1-month (P \u3c 0.001) higher GAA, respectively. A statistical interaction between marijuana-years and alcohol consumption on GAA was observed (P = 0.011), with nondrinkers exhibiting a higher GAA (β = 0.21 [95% CI 0.05, 0.36], P = 0.008) compared to heavy drinkers (β = 0.05 [95% CI - 0.09, 0.18], P = 0.500) per each additional marijuana-year. No associations were observed for the remaining EAA estimates. CONCLUSIONS: These findings suggest cumulative and recent marijuana use are associated with age-related epigenetic changes that are related to lifespan. These observed associations may be modified by alcohol consumption. Given the increase in use and legalization, these findings provide novel insight on the effect of marijuana use on the aging process as captured through blood DNA methylation

Brain-computer interface algorithm based on wavelet-phase stability analysis in motor imagery experiment

Severe movement or motor disability diseases such as amyotrophic lateral sclerosis (ALS), cerebral palsy (CB), and muscular dystrophy (MD) are types of diseases which lead to the total of function loss of body parts, usually limbs. Patient with an extreme motor impairment might suffers a lockedin state, resulting in the difficulty to perform any physical movements. These diseases are commonly being treated by a specific rehabilitation procedure with prescribed medication. However, the recovery process is time-consuming through such treatments. To overcome these issues, Brain- Computer Interface system is introduced in which one of its modalities is to translate thought via electroencephalography (EEG) signals by the user and generating desired output directly to an external artificial control device or human augmentation. Here, phase synchronization is implemented to complement the BCI system by analyzing the phase stability between two input signals. The motor imagery-based experiment involved ten healthy subjects aged from 24 to 30 years old with balanced numbers between male and female. Two aforementioned input signals are the respective reference data and the real time data were measured by using phase stability technique by indicating values range from 0 (least stable) to 1 (most stable). Prior to that, feature extraction was utilized by applying continuous wavelet transform (CWT) to quantify significant features on the basis of motor imagery experiment which are right and left imaginations. The technique was able to segregate different classes of motor imagery task based on classification accuracy. This study affirmed the approach’s ability to achieve high accuracy output measurements

Formulation of a novel HRV classification model as a surrogate fraudulence detection schema

Lie detection has been studied since a few decades ago, usually for the purpose of producing a scheme to assist in the investigation of identifying the culprit from a list of suspects. Heart Rate Variability (HRV) may be used as a method in lie detection due to its versatility and suitability. However, since its analysis is not instantaneous, a new experiment is described in this paper to overcome the problem. Additionally, a preliminary HRV classification model is designed to further enhance the classification model which is able to distinguish the lie from the truth for up to 80%

Capturing Hammerhead Ribozyme Structures in Action by Modulating General Base Catalysis

We have obtained precatalytic (enzyme–substrate complex) and postcatalytic (enzyme–product complex) crystal structures of an active full-length hammerhead RNA that cleaves in the crystal. Using the natural satellite tobacco ringspot virus hammerhead RNA sequence, the self-cleavage reaction was modulated by substituting the general base of the ribozyme, G12, with A12, a purine variant with a much lower pKa that does not significantly perturb the ribozyme's atomic structure. The active, but slowly cleaving, ribozyme thus permitted isolation of enzyme–substrate and enzyme–product complexes without modifying the nucleophile or leaving group of the cleavage reaction, nor any other aspect of the substrate. The predissociation enzyme-product complex structure reveals RNA and metal ion interactions potentially relevant to transition-state stabilization that are absent in precatalytic structures

Theory and phenomenology of two-Higgs-doublet models

We discuss theoretical and phenomenological aspects of two-Higgs-doublet extensions of the Standard Model. In general, these extensions have scalar mediated flavour changing neutral currents which are strongly constrained by experiment. Various strategies are discussed to control these flavour changing scalar currents and their phenomenological consequences are analysed. In particular, scenarios with natural flavour conservation are investigated, including the so-called type I and type II models as well as lepton-specific and inert models. Type III models are then discussed, where scalar flavour changing neutral currents are present at tree level, but are suppressed by either specific ansatze for the Yukawa couplings or by the introduction of family symmetries. We also consider the phenomenology of charged scalars in these models. Next we turn to the role of symmetries in the scalar sector. We discuss the six symmetry-constrained scalar potentials and their extension into the fermion sector. The vacuum structure of the scalar potential is analysed, including a study of the vacuum stability conditions on the potential and its renormalization-group improvement. The stability of the tree level minimum of the scalar potential in connection with electric charge conservation and its behaviour under CP is analysed. The question of CP violation is addressed in detail, including the cases of explicit CP violation and spontaneous CP violation. We present a detailed study of weak basis invariants which are odd under CP. A careful study of spontaneous CP violation is presented, including an analysis of the conditions which have to be satisfied in order for a vacuum to violate CP. We present minimal models of CP violation where the vacuum phase is sufficient to generate a complex CKM matrix, which is at present a requirement for any realistic model of spontaneous CP violation.Comment: v3: 180 pages, 506 references, new chapter 7 with recent LHC results; referee comments taken into account; submitted to Physics Report