Health Coaching: An Update on the National Consortium for Credentialing of Health & Wellness Coaches

In September 2014, Global Advances in Health and Medicine editor Michele Mittelman, RN, MPH, interviewed four of the leaders in health and wellness coaching about trends in coaching and the progress of the National Consortium for Credentialing of Health & Wellness Coaches. Following are the transcripts of those interviews. Additionally, videos of the interviews are available at www.gahmj.com .

Inaugural Osher Integrative Medicine Research Forum: An Overview

Those who attended the Inaugural Integrative Medicine Research Forum hosted by the Osher Center for Integrative Medicine at Harvard Medical School (HMS) and Brigham and Women's Hospital, Boston, Masssachusetts, had the unique experience of viewing an interactive research network, 670 individuals representing 19 different institutions, seeing poster presentations from 38 investigators, and hearing presentations that described impressive clinical and educational programs that are underway in the Boston area. Throughout the proceedings, two themes emerged: conventional medicine has suffered from artificial boundaries, and collaboration is essential if integrative medicine is to fulfill its promise. The forum, held on November 3, 2014, is widely considered as having been pivotal and historic: for the first time, Boston-wide research activity was presented and quantified. This led Helene Langevin, MD, Osher Center Director, to call for a new era of collaboration. “We must continue to build bridges, cultivate c...

Structure of a low-population intermediate state in the release of an enzyme product

Enzymes can increase the rate of biomolecular reactions by several orders of magnitude. Although the steps of substrate capture and product release are essential in the enzymatic process, complete atomic-level descriptions of these steps are difficult to obtain because of the transient nature of the intermediate conformations, which makes them largely inaccessible to standard structure determination methods. We describe here the determination of the structure of a low-population intermediate in the product release process by human lysozyme through a combination of NMR spectroscopy and molecular dynamics simulations. We validate this structure by rationally designing two mutations, the first engineered to destabilise the intermediate and the second to stabilise it, thus slowing down or speeding up, respectively, product release. These results illustrate how product release by an enzyme can be facilitated by the presence of a metastable intermediate with transient weak interactions between the enzyme and product.

Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.

Kin cell lysis is a danger signal that activates antibacterial pathways of Pseudomonas aeruginosa

The perception and response to cellular death is an important aspect of multicellular eukaryotic life. For example, damage-associated molecular patterns activate an inflammatory cascade that leads to removal of cellular debris and promotion of healing. We demonstrate that lysis of Pseudomonas aeruginosa cells triggers a program in the remaining population that confers fitness in interspecies co-culture. We find that this program, termed P. aeruginosa response to antagonism (PARA), involves rapid deployment of antibacterial factors and is mediated by the Gac/Rsm global regulatory pathway. Type VI secretion, and, unexpectedly, conjugative type IV secretion within competing bacteria, induce P. aeruginosa lysis and activate PARA, thus providing a mechanism for the enhanced capacity of P. aeruginosa to target bacteria that elaborate these factors. Our finding that bacteria sense damaged kin and respond via a widely distributed pathway to mount a complex response raises the possibility that danger sensing is an evolutionarily conserved process.

MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA

To avoid mutations in the genome, DNA replication is generally followed by DNA mismatch repair (MMR). MMR starts when a MutS homolog recognizes a mismatch and undergoes an ATP-dependent transformation to an elusive sliding clamp state. How this transient state promotes MutL homolog recruitment and activation of repair is unclear. Here we present a crystal structure of the MutS/MutL complex using a site-specifically crosslinked complex and examine how large conformational changes lead to activation of MutL. The structure captures MutS in the sliding clamp conformation, where tilting of the MutS subunits across each other pushes DNA into a new channel, and reorientation of the connector domain creates an interface for MutL with both MutS subunits. Our work explains how the sliding clamp promotes loading of MutL onto DNA, to activate downstream effectors. We thus elucidate a crucial mechanism that ensures that MMR is initiated only after detection of a DNA mismatch.

Correction: Fluorescent sensors reporting the activity of ammonium transceptors in live cells

Single-fluorophore membrane transport activity sensors with dual-emission read-out

We recently described a series of genetically encoded, single-fluorophore-based sensors, termed AmTrac and MepTrac, which monitor membrane transporter activity in vivo ( De Michele et al., 2013 ). However, being intensiometric, AmTrac and Meptrac are limited in their use for quantitative studies. Here, we characterized the photophysical properties (steady-state and time-resolved fluorescence spectroscopy as well as anisotropy decay analysis) of different AmTrac sensors with diverging fluorescence properties in order to generate improved, ratiometric sensors. By replacing key amino acid residues in AmTrac we constructed a set of dual-emission AmTrac sensors named deAmTracs. deAmTracs show opposing changes of blue and green emission with almost doubled emission ratio upon ammonium addition. The response ratio of the deAmTracs correlated with transport activity in mutants with altered capacity. Our results suggest that partial disruption of distance-dependent excited-state proton transfer is important for the successful generation of single-fluorophore-based dual-emission sensors.

Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes

Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predicted by the model, and experimentally supported. The analysis suggests that the rate-limiting step of hydrolysis is the transport of the substrates into the proteasome. The transport efficiency varies between human standard- and immuno-proteasomes thereby impinging upon total degradation rate and substrate cleavage-site usage.

Baseline Hematologic Results for Free-ranging White Rhinoceros (Ceratotherium simum) in Kruger National Park, South Africa

Complete blood counts (n = 115) and red blood cell analytes (n = 80) were assessed in free-ranging white rhinoceros (Ceratotherium simum) from Kruger National Park (KNP), South Africa. Blood was collected from healthy animals immobilized between February and September 2009-11 for management purposes. Our objectives were to establish baselines for KNP's white rhinoceros population and to compare results based on sex and age group. Significant differences in total white blood cells, total eosinophils, and hemoglobin were found between adult and subadult rhinoceros. Female rhinoceros had significantly higher total white blood cells and lower hemoglobin compared with males. Hematologic analytes were similar to those published for other rhinoceros populations, although the impact of capture and sampling methods, nutritional status, and habitat should be considered when comparing data. This baseline hematology for healthy free-ranging white rhinoceros in KNP may be useful in assessing health status for translocation and medical interventions, including treatment of poaching cases.