Adverse childhood experiences and mental health in young adults: a longitudinal survey

BACKGROUND: Adverse childhood experiences (ACEs) have been consistently linked to psychiatric difficulties in children and adults. However, the long-term effects of ACEs on mental health during the early adult years have been understudied. In addition, many studies are methodologically limited by use of non-representative samples, and few studies have investigated gender and racial differences. The current study relates self-reported lifetime exposure to a range of ACEs in a community sample of high school seniors to three mental health outcomes–depressive symptoms, drug abuse, and antisocial behavior–two years later during the transition to adulthood. METHODS: The study has a two-wave, prospective design. A systematic probability sample of high school seniors (N = 1093) was taken from communities of diverse socioeconomic status. They were interviewed in person in 1998 and over the telephone two years later. Gender and racial differences in ACE prevalence were tested with chi-square tests. Each mental health outcome was regressed on one ACE, controlling for gender, race/ethnicity, and SES to obtain partially standardized regression coefficients. RESULTS: Most ACEs were strongly associated with all three outcomes. The cumulative effect of ACEs was significant and of similar magnitude for all three outcomes. Except for sex abuse/assault, significant gender differences in the effects of single ACEs on depression and drug use were not observed. However, boys who experienced ACEs were more likely to engage in antisocial behavior early in young adulthood than girls who experienced similar ACEs. Where racial/ethnic differences existed, the adverse mental health impact of ACEs on Whites was consistently greater than on Blacks and Hispanics. CONCLUSION: Our sample of young adults from urban, socio-economically disadvantaged communities reported high rates of adverse childhood experiences. The public health impact of childhood adversity is evident in the very strong association between childhood adversity and depressive symptoms, antisocial behavior, and drug use during the early transition to adulthood. These findings, coupled with evidence that the impact of major childhood adversities persists well into adulthood, indicate the critical need for prevention and intervention strategies targeting early adverse experiences and their mental health consequences

Low-Temperature Preparation of Superparamagnetic CoFe2O4 Microspheres with High Saturation Magnetization

Based on a low-temperature route, monodispersed CoFe2O4 microspheres (MSs) were fabricated through aggregation of primary nanoparticles. The microstructural and magnetic characteristics of the as-prepared MSs were characterized by X-ray diffraction/photoelectron spectroscopy, scanning/transmitting electron microscopy, and vibrating sample magnetometer. The results indicate that the diameters of CoFe2O4 MSs with narrow size distribution can be tuned from over 200 to ~330 nm. Magnetic measurements reveal these MSs exhibit superparamagnetic behavior at room temperature with high saturation magnetization. Furthermore, the mechanism of formation of the monodispersed CoFe2O4 MSs was discussed on the basis of time-dependent experiments, in which hydrophilic PVP plays a crucial role

Mismatch Repair–Independent Increase in Spontaneous Mutagenesis in Yeast Lacking Non-Essential Subunits of DNA Polymerase ε

Yeast DNA polymerase ε (Pol ε) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template. In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol ε also has one essential subunit (Dpb2) and two smaller, non-essential subunits (Dpb3 and Dpb4) whose functions are not fully understood. To probe the functions of Dpb3 and Dpb4, here we investigate the consequences of their absence on the biochemical properties of Pol ε in vitro and on genome stability in vivo. The fidelity of DNA synthesis in vitro by purified Pol2/Dpb2, i.e. lacking Dpb3 and Dpb4, is comparable to the four-subunit Pol ε holoenzyme. Nonetheless, deletion of DPB3 and DPB4 elevates spontaneous frameshift and base substitution rates in vivo, to the same extent as the loss of Pol ε proofreading activity in a pol2-4 strain. In contrast to pol2-4, however, the dpb3Δdpb4Δ does not lead to a synergistic increase of mutation rates with defects in DNA mismatch repair. The increased mutation rate in dpb3Δdpb4Δ strains is partly dependent on REV3, as well as the proofreading capacity of Pol δ. Finally, biochemical studies demonstrate that the absence of Dpb3 and Dpb4 destabilizes the interaction between Pol ε and the template DNA during processive DNA synthesis and during processive 3′ to 5′exonucleolytic degradation of DNA. Collectively, these data suggest a model wherein Dpb3 and Dpb4 do not directly influence replication fidelity per se, but rather contribute to normal replication fork progression. In their absence, a defective replisome may more frequently leave gaps on the leading strand that are eventually filled by Pol ζ or Pol δ, in a post-replication process that generates errors not corrected by the DNA mismatch repair system

Revealing Higher Order Protein Structure Using Mass Spectrometry

International audienceThe development of rapid, sensitive, and accurate mass spectrometric methods for measuring peptides, proteins, and even intact protein assemblies has made mass spectrometry (MS) an extraordinarily enabling tool for structural biology. Here, we provide a personal perspective of the increasingly useful role that mass spectrometric techniques are exerting during the elucidation of higher order protein structures. Areas covered in this brief perspective include MS as an enabling tool for the high resolution structural biologist, for compositional analysis of endogenous protein complexes, for stoichiometry determination, as well as for integrated approaches for the structural elucidation of protein complexes. We conclude with a vision for the future role of MS-based techniques in the development of a multi-scale molecular microscope

Metaproteomics reveals potential mechanisms by which dietary resistant starch supplementation attenuates chronic kidney disease progression in rats.

BACKGROUND:Resistant starch is a prebiotic metabolized by the gut bacteria. It has been shown to attenuate chronic kidney disease (CKD) progression in rats. Previous studies employed taxonomic analysis using 16S rRNA sequencing and untargeted metabolomics profiling. Here we expand these studies by metaproteomics, gaining new insight into the host-microbiome interaction. METHODS:Differences between cecum contents in CKD rats fed a diet containing resistant starch with those fed a diet containing digestible starch were examined by comparative metaproteomics analysis. Taxonomic information was obtained using unique protein sequences. Our methodology results in quantitative data covering both host and bacterial proteins. RESULTS:5,834 proteins were quantified, with 947 proteins originating from the host organism. Taxonomic information derived from metaproteomics data surpassed previous 16S RNA analysis, and reached species resolutions for moderately abundant taxonomic groups. In particular, the Ruminococcaceae family becomes well resolved-with butyrate producers and amylolytic species such as R. bromii clearly visible and significantly higher while fibrolytic species such as R. flavefaciens are significantly lower with resistant starch feeding. The observed changes in protein patterns are consistent with fiber-associated improvement in CKD phenotype. Several known host CKD-associated proteins and biomarkers of impaired kidney function were significantly reduced with resistant starch supplementation. Data are available via ProteomeXchange with identifier PXD008845. CONCLUSIONS:Metaproteomics analysis of cecum contents of CKD rats with and without resistant starch supplementation reveals changes within gut microbiota at unprecedented resolution, providing both functional and taxonomic information. Proteins and organisms differentially abundant with RS supplementation point toward a shift from mucin degraders to butyrate producers

Metaproteomics reveals potential mechanisms by which dietary resistant starch supplementation attenuates chronic kidney disease progression in rats.

BACKGROUND:Resistant starch is a prebiotic metabolized by the gut bacteria. It has been shown to attenuate chronic kidney disease (CKD) progression in rats. Previous studies employed taxonomic analysis using 16S rRNA sequencing and untargeted metabolomics profiling. Here we expand these studies by metaproteomics, gaining new insight into the host-microbiome interaction. METHODS:Differences between cecum contents in CKD rats fed a diet containing resistant starch with those fed a diet containing digestible starch were examined by comparative metaproteomics analysis. Taxonomic information was obtained using unique protein sequences. Our methodology results in quantitative data covering both host and bacterial proteins. RESULTS:5,834 proteins were quantified, with 947 proteins originating from the host organism. Taxonomic information derived from metaproteomics data surpassed previous 16S RNA analysis, and reached species resolutions for moderately abundant taxonomic groups. In particular, the Ruminococcaceae family becomes well resolved-with butyrate producers and amylolytic species such as R. bromii clearly visible and significantly higher while fibrolytic species such as R. flavefaciens are significantly lower with resistant starch feeding. The observed changes in protein patterns are consistent with fiber-associated improvement in CKD phenotype. Several known host CKD-associated proteins and biomarkers of impaired kidney function were significantly reduced with resistant starch supplementation. Data are available via ProteomeXchange with identifier PXD008845. CONCLUSIONS:Metaproteomics analysis of cecum contents of CKD rats with and without resistant starch supplementation reveals changes within gut microbiota at unprecedented resolution, providing both functional and taxonomic information. Proteins and organisms differentially abundant with RS supplementation point toward a shift from mucin degraders to butyrate producers