Critical analysis of polycyclic tetramate macrolactam biosynthetic gene cluster phylogeny and functional diversity.

Polycyclic tetramate macrolactams (PTMs) are bioactive natural products commonly associated with certain actinobacterial and proteobacterial lineages. These molecules have been the subject of numerous structure-activity investigations since the 1970s. New members continue to be pursued in wild and engineered bacterial strains, and advances in PTM biosynthesis suggest their outwardly simplistic biosynthetic gene clusters (BGCs) belie unexpected product complexity. To address the origins of this complexity and understand its influence on PTM discovery, we engaged in a combination of bioinformatics to systematically classify PTM BGCs and PTM-targeted metabolomics to compare the products of select BGC types. By comparing groups of producers and BGC mutants, we exposed knowledge gaps that complicate bioinformatics-driven product predictions. In sum, we provide new insights into the evolution of PTM BGCs while systematically accounting for the PTMs discovered thus far. The combined computational and metabologenomic findings presented here should prove useful for guiding future discovery.IMPORTANCEPolycyclic tetramate macrolactam (PTM) pathways are frequently found within the genomes of biotechnologically important bacteria, including Streptomyces and Lysobacter spp. Their molecular products are typically bioactive, having substantial agricultural and therapeutic interest. Leveraging bacterial genomics for the discovery of new related molecules is thus desirable, but drawing accurate structural predictions from bioinformatics alone remains challenging. This difficulty stems from a combination of previously underappreciated biosynthetic complexity and remaining knowledge gaps, compounded by a stream of yet-uncharacterized PTM biosynthetic loci gleaned from recently sequenced bacterial genomes. We engaged in the following study to create a useful framework for cataloging historic PTM clusters, identifying new cluster variations, and tracing evolutionary paths for these molecules. Our data suggest new PTM chemistry remains discoverable in nature. However, our metabolomic and mutational analyses emphasize the practical limitations of genomics-based discovery by exposing hidden complexity.

Draft Genome Sequences of Two Polycyclic Tetramate Macrolactam Producers, Streptomyces sp. Strains JV180 and SP18CM02.

Here, we report the draft genome sequences of two related Streptomyces sp. strains, JV180 and SP18CM02. Despite their isolation from soils in Connecticut and Missouri (USA), respectively, they are strikingly similar in gene content. Both belong to the Streptomyces griseus clade and harbor several secondary metabolite biosynthetic gene clusters.

Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: externalizing and internalizing subtypes.

This study used the Multidimensional Personality Questionnaire (MPQ; A. Tellegen, in press) to identify personality-based subtypes of posttraumatic response. Cluster analyses of MPQs completed by combat veterans revealed subgroups that differed on measures relating to the externalization versus internalization of distress. The MPQ profile of the externalizing cluster was defined by low Constraint and Harmavoidance coupled with high Alienation and Aggression. Individuals in this cluster also had histories of delinquency and high rates of substance-related disorder. In comparison, the MPQ profile of the internalizing cluster was characterized by lower Positive Emotionality, Alienation, and Aggression and higher Constraint, and individuals in this cluster showed high rates of depressive disorder. These findings suggest that dispositions toward externalizing versus internalizing psychopathology may account for heterogeneity in the expression of posttraumatic responses, including patterns of comorbidity.

Preventive health behaviors, health-risk behaviors, physical morbidity, and health-related role functioning impairment in veterans with post-traumatic stress disorder.

An examination of the relationships between health behaviors (preventive and risk-related), physician-diagnosed medical problems, role-functioning impairment because of physical morbidity, and post-traumatic stress disorder was conducted on a large cohort of consecutive treatment-seeking cases (N = 826) presenting to an outpatient Veterans Affairs post-traumatic stress disorder clinic. Results revealed that the sample rates of several medical conditions were markedly elevated when compared with general population rates for men of comparable age. The rates of smoking and other behavioral risk variables were greater than rates among men in the general population. Moreover, the majority of the sample did not engage in preventive health behaviors such as exercise and medical screening at levels consistent with health care guidelines. Physical role functioning indices of the SF-36 reveal greater role-functioning impairment because of physical morbidity in this psychiatric sample relative to the age adjusted general population norms. The health care implications of these data are discussed, as are areas for future research.

International publication trends in the traumatic stress literature.

This analysis looked at international publication trends in the field of trauma by examining first author affiliations of over 13,000 trauma publications from 1987 to 2001. Searches were conducted using the Published International Literature on Traumatic Stress (PILOTS) database to determine frequency of international contributions. A similar search of the Journal of Traumatic Stress (JTS) was also conducted. Although the majority of trauma research comes from investigators in North America, examining publication trends over time revealed that trauma research is becoming increasingly international in its representation. Results suggest that of the overall trauma literature, 36% of contributions come from authors outside North America. Likewise, among JTS publications over the first 14 years of circulation, 27% came from authors outside North America. More recent publication years reflect higher levels of international contributions for both sources. The majority of trauma research published over the 15-year span was in English. Implications for the field of traumatic stress research are discussed.

Twenty-four-hour ambulatory assessment of heart rate and blood pressure in chronic PTSD and non-PTSD veterans.

This study examined 24-hr levels of ambulatory heart rate (HR) and blood pressure (BP) in 2 groups of male veterans: 19 with chronic posttraumatic stress disorder (PTSD) and 17 who never met criteria for PTSD. The relationships between diagnostic status, basal cardiovascular activity, and cardiovascular reactivity to stress were examined. Hierarchical linear modeling analyses revealed that the PTSD group had higher resting HR than the non-PTSD group. Moreover, the PTSD group showed greater BP reactivity during times of affective distress than the non-PTSD group. The health care implications of these findings are discussed, as are directions for future research.