A Model of Proto-Anti-Codon RNA Enzymes Requiring l-Amino Acid Homochirality

All living organisms encode the 20 natural amino acid units of polypeptides using a universal scheme of triplet nucleotide “codons”. Disparate features of this codon scheme are potentially informative of early molecular evolution: (i) the absence of any codons for d-amino acids; (ii) the odd combination of alternate codon patterns for some amino acids; (iii) the confinement of synonymous positions to a codon’s third nucleotide; (iv) the use of 20 specific amino acids rather than a number closer to the full coding potential of 64; and (v) the evolutionary relationship of patterns in stop codons to amino acid codons. Here I propose a model for an ancestral proto-anti-codon RNA (pacRNA) auto-aminoacylation system and show that pacRNAs would naturally manifest features of the codon table. I show that pacRNAs could implement all the steps for auto-aminoacylation: amino acid coordination, intermediate activation of the amino acid by the 5′-end of the pacRNA, and 3′-aminoacylation of the pacRNA. The anti-codon cradles of pacRNAs would have been able to recognize and coordinate only a small number of l-amino acids via hydrogen bonding. A need for proper spatial coordination would have limited the number of chargeable amino acids for all anti-codon sequences, in addition to making some anti-codon sequences unsuitable. Thus, the pacRNA model implies that the idiosyncrasies of the anti-codon table and l-amino acid homochirality co-evolved during a single evolutionary period. These results further imply that early life consisted of an aminoacylated RNA world with a richer enzymatic potential than ribonucleotides alone

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Both Trait and State Mindfulness Predict Lower Aggressiveness via Anger Rumination: a Multilevel Mediation Analysis

Trait mindfulness, or the capacity for nonjudgmental, present-centered attention, predicts lower aggression in cross-sectional samples, an effect mediated by reduced anger rumination. Experimental work also implicates state mindfulness (i.e., fluctuations around one's typical mindfulness) in aggression. Despite evidence that both trait and state mindfulness predict lower aggression, their relative impact and their mechanisms remain unclear. Higher trait mindfulness and state increases in mindfulness facets may reduce aggression-related outcomes by (1) limiting the intensity of anger, or (2) limiting rumination on anger experiences. The present study tests two hypotheses: First, that both trait and state mindfulness contribute unique variance to lower aggressiveness, and second, that the impact of both trait and state mindfulness on aggressiveness will be uniquely partially mediated by both anger intensity and anger rumination. 86 participants completed trait measures of mindfulness, anger intensity, and anger rumination, then completed diaries for 35 days assessing mindfulness, anger intensity, anger rumination, anger expression, and self-reported and behavioral aggressiveness. Using multilevel zero-inflated regression, we examined unique contributions of trait and state mindfulness facets to daily anger expression and aggressiveness. We also examined the mediating roles of anger intensity and anger rumination at both trait and state levels. Mindfulness facets predicted anger expression and aggressiveness indirectly through anger rumination after controlling for indirect pathways through anger intensity. Individuals with high or fluctuating aggression may benefit from mindfulness training to reduce both intensity of and rumination on anger

Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family

Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and Western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild-type, suggesting a deleterious effect of the sequence variant