Human gut microbiome adopts an alternative state following small bowel transplantation

Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. The ileostomy created at time of transplant for ongoing monitoring of the allograft provides access to samples of ileal effluent and mucosal biopsies. In this study, we used qPCR to assay the bacterial population of the small bowel lumen of 17 small bowel transplant patients over time. Surprisingly, the posttransplant microbial community was found to be dominated by Lactobacilli and Enterobacteria, both typically facultative anaerobes. This represents an inversion of the normal community that is dominated instead by the strictly anaerobic Bacteroides and Clostridia. We found this inverted community also in patients with ileostomies who did not receive a transplant, suggesting that the ileostomy itself is the primary ecological determinant shaping the microbiota. After surgical closure of the ileostomy, the community reverted to the normal structure. Therefore, we hypothesized that the ileostomy allows oxygen into the otherwise anaerobic distal ileum, thus driving the transition from one microbial community structure to another. Supporting this hypothesis, metabolomic profiling of both communities demonstrated an enrichment for metabolites associated with aerobic respiration in samples from patients with open ileostomies. Viewed from an ecological perspective, the two communities constitute alternative stable states of the human ileum. That the small bowel appears to function normally despite these dramatic shifts suggests that its ecological resilience is greater than previously realized.     

The Revised Commitment Inventory: Psychometrics and Use with Unmarried Couples

The Commitment Inventory (Stanley & Markman, 1992) measures interpersonal commitment (dedication) and constraint commitment. Since it was first published, substantial revisions have been made, but there are no published data on the psychometric properties of the new version. Further, little information is available on measuring commitment for unmarried couples. This study examined the psychometric properties of the Commitment Inventory in 320 premarital or cohabiting couples (N = 640). Dyadic confirmatory factor analyses revealed that the hypothesized factor structure of six constraint subscales and one dedication subscale fit the data well for both men and women. Internal consistency coefficients were within acceptable range for most subscales. Within-couple correlations as well as correlations among subscales and with relationship quality, negative communication, and religiosity are presented. Implications for future research are discussed.     

Screening for Cardiovascular Disease in the Young

America's youth have been screened for cardiovascular disorders for nearly a century. Initial efforts to detect rheumatic heart disease in schoolchildren have gradually shifted to the detection of congenital heart disease in the fetus and newborn, and to the prevention of sudden cardiac death in older children, especially athletes. Proposed screening programs need to consider sensitivity and specificity, cost, resource availability, and the potential for adverse effects of the screening process.     

Effect of transmurally heterogeneous myocyte excitation–contraction coupling on canine left ventricular electromechanics

The excitation–contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We embedded a cell-level excitation–contraction coupling model with region-dependent parameters within a simple finite element model of left ventricular geometry to study effects of electromechanical heterogeneity on local myocardial mechanics and global haemodynamics. This model was compared with one in which heterogeneous myocyte parameters were assigned randomly throughout the mesh while preserving the total amount of each cell subtype. The two models displayed nearly identical transmural patterns of fibre and cross-fibre strains at end-systole, but showed clear differences in fibre strains at earlier points during systole. Haemodynamic function, including peak left ventricular pressure, maximal rate of left ventricular pressure development and stroke volume, were essentially identical in the two models. These results suggest that in the intact ventricle heterogeneously distributed myocyte subtypes primarily impact local deformation of the myocardium, and that these effects are greatest during early systole.     

Mitochondrial ribonuclease P structure provides insight into the evolution of catalytic strategies for precursor-tRNA 5′ processing

Ribonuclease P (RNase P) catalyzes the maturation of the 5′ end of tRNA precursors. Typically these enzymes are ribonucleoproteins with a conserved RNA component responsible for catalysis. However, protein-only RNase P (PRORP) enzymes process precursor tRNAs in human mitochondria and in all tRNA-using compartments of Arabidopsis thaliana. PRORP enzymes are nuclear encoded and conserved among many eukaryotes, having evolved recently as yeast mitochondrial genomes encode an RNase P RNA. Here we report the crystal structure of PRORP1 from A. thaliana at 1.75 Å resolution, revealing a prototypical metallonuclease domain tethered to a pentatricopeptide repeat (PPR) domain by a structural zinc-binding domain. The metallonuclease domain is a unique high-resolution structure of a Nedd4-BP1, YacP Nucleases (NYN) domain that is a member of the PIN domain-like fold superfamily, including the FLAP nuclease family. The structural similarity between PRORP1 and the FLAP nuclease family suggests that they evolved from a common ancestor. Biochemical data reveal that conserved aspartate residues in PRORP1 are important for catalytic activity and metal binding and that the PPR domain also enhances activity, likely through an interaction with pre-tRNA. These results provide a foundation for understanding tRNA maturation in organelles. Furthermore, these studies allow for a molecular-level comparison of the catalytic strategies used by the only known naturally evolved protein and RNA-based catalysts that perform the same biological function, pre-tRNA maturation, thereby providing insight into the differences between the prebiotic RNA world and the present protein-dominated world.