Neural development: Identical twins separated at birth?

AbstractA combination of time-lapse analysis of developing brain slices in vitro and the cloning of genes involved in determining cell fate has demonstrated the remarkable similarities between early neurogenetic events in vertebrates and invertebrates

Nature\u27s Assembly Line Logic for Natural Products

Nature fashions a very large number of diverse products (molecular weights ranging from ca. 200 to 2000 daltons) from simple monomeric metabolites used in primary metabolism. These include polyketide scaffolds generated from the simple C₃ malonyl CoA and C₄ methylmalonyl CoA monomers and nonribosomal peptides made from both the 20 proteinogenic amino acids and dozens of nonpoteinogenic amino acids.¹ A large family of terpenoid skeletons are built from the Δ²- and Δ³-alkene isomers of the biological isoprene monomer, isoprenyl-pyrophosphate.

Outcome following valve surgery in Australia: Development of an enhanced database module

Background: Valvular heart disease, including rheumatic heart disease (RHD), is an important cause of heart disease globally. Management of advanced disease can include surgery and other interventions to repair or replace affected valves. This article summarises the methodology of a study that will incorporate enhanced data collection systems to provide additional insights into treatment choice and outcome for advanced valvular disease including that due to RHD. Methods: An enhanced data collection system will be developed linking an existing Australian cardiac surgery registry to more detailed baseline co-morbidity, medication, echocardiographic and hospital separation data to identify predictors of morbidity and mortality outcome following valve surgery. Discussion: This project aims to collect and incorporate more detailed information regarding pre and postoperative factors and subsequent morbidity. We will use this to provide additional insights into treatment choice and outcome. © 2017 The Author(s)

Elemental Abundances of Nearby Galaxies through High Signal-to-Noise XMM-Newton Observations of ULXs

(abridged) In this paper, we examined XMM Newton EPIC spectra of 14 ultra-luminous X-ray sources (ULXs)in addition to the XMM RGS spectra of two sources (Holmberg II X-1 and Holmberg IX X-1). We determined oxygen and iron abundances of the host galaxy's interstellar medium (ISM) using K-shell (O) and L-shell (Fe) X-ray photo-ionization edges towards these ULXs. We found that the oxygen abundances closely matched recent solar abundances for all of our sources, implying that ULXs live in similar local environments despite the wide range of galaxy host properties. Also, we compare the X-ray hydrogen column densities (n_H) for 8 ULX sources with column densities obtained from radio H I observations. The X-ray model n_H values are in good agreement with the H I n_H values, implying that the hydrogen absorption towards the ULXs is not local to the source (with the exception of the source M81 XMM1). In order to obtain the column density and abundance values, we fit the X-ray spectra of the ULXs with a combined power law and one of several accretion disk models. We tested the abundances obtained from the XSPEC models bbody, diskbb, grad, and diskpn along with a power law, finding that the abundances were independent of the thermal model used. We comment on the physical implications of these different model fits. We also note that very deep observations allow a breaking of the degeneracy noted by Stobbart et al. (2006) favoring a high mass solution for the absorbed grad + power law model.Comment: 18 pages, accepted to Ap

Macrolactamization of Glycosylated Peptide Thioesters by the Thioesterase Domain of Tyrocidine Synthetase

SummaryThe 35 kDa thioesterase (TE) domain excised from the megadalton tyrocidine synthetase (Tyc Syn) retains autonomous capacity to macrocyclize peptidyl thioesters to D-Phe1-L-Leu10-macrolactams. Since a number of nonribosomal peptides undergo O-glycosylation events during tailoring to gain biological activity, the Tyc Syn TE domain was evaluated for cyclization capacity with glycosylated peptidyl-S-NAC substrates. First, Tyr7 was replaced with Tyr(β-D-Gal) and Tyr(β-D-Glc) as well as with Ser-containing β-linked D-Gal, D-Glc, D-GlcNAc, and D-GlcNH2, and these new analogs were shown to be cyclized with comparable kcat/Km catalytic efficiency. Similarly, Gal- or tetra-O-acetyl-Gal-Ser could also be substituted at residues 5, 6, and 8 in the linear decapeptidyl-S-NAC sequences and cyclized without substantial loss in catalytic efficiency by Tyc Syn TE. The cyclic glycopeptides retained antibiotic activity as membrane perturbants in MIC assays, opening the possibility for library construction of cyclic glycopeptides by enzymatic macrocyclization

What and How Do Students Learn in an Interprofessional Student-Run Clinic? An Educational Framework for Team-Based Care

Background: The student-run clinic (SRC) has the potential to address interprofessional learning among health professions students. Purpose: To derive a framework for understanding student learning during team-based care provided in an interprofessional SRC serving underserved patients. Methods: The authors recruited students for a focus group study by purposive sampling and snowballing. They constructed two sets of semi-structured questions for uniprofessional and multiprofessional groups. Sessions were audiotaped, and transcripts were independently coded and adjudicated. Major themes about learning content and processes were extracted. Grounded theory was followed after data synthesis and interpretation to establish a framework for interprofessional learning. Results: Thirty-six students from four professions (medicine, physician assistant, occupational therapy, and pharmacy) participated in eight uniprofessional groups; 14 students participated in three multiprofessional groups (N50). Theme saturation was achieved. Six common themes about learning content from uniprofessional groups were role recognition, team-based care appreciation, patient experience, advocacy-/systemsbased models, personal skills, and career choices. Occupational therapy students expressed self-advocacy, and medical students expressed humility and self-discovery. Synthesis of themes from all groups suggests a learning continuum that begins with the team huddle and continues with shared patient care and social interactions. Opportunity to observe and interact with other professions in action is key to the learning process. Discussion: Interprofessional SRC participation promotes learning ‘with, from, and about’ each other. Participation challenges misconceptions and sensitizes students to patient experiences, health systems, advocacy, and social responsibility. Learning involves interprofessional interactions in the patient encounter, reinforced by formal and informal communications. Participation is associated with interest in serving the underserved and in primary care careers. The authors proposed a framework for interprofessional learning with implications for optimal learning environments to promote team-based care. Future research is suggested to identify core faculty functions and best settings to advance and enhance student preparation for future collaborative team practice

When Less is More: Validating a Brief Scale to Rate Interprofessional Team Competencies

Background: There is a need for validated and easy-to-apply behavior-based tools for assessing interprofessional team competencies in clinical settings. The seven-item observerbased Modified McMaster-Ottawa scale was developed for the Team Objective Structured Clinical Encounter (TOSCE) to assess individual and team performance in interprofessional patient encounters. Objective: We aimed to improve scale usability for clinical settings by reducing item numbers while maintaining generalizability; and to explore the minimum number of observed cases required to achieve modest generalizability for giving feedback. Design: We administered a two-station TOSCE in April 2016 to 63 students split into 16 newly-formed teams, each consisting of four professions. The stations were of similar difficulty. We trained sixteen faculty to rate two teams each. We examined individual and team performance scores using generalizability (G) theory and principal component analysis (PCA). Results: The seven-item scale shows modest generalizability (.75) with individual scores. PCA revealed multicollinearity and singularity among scale items and we identified three potential items for removal. Reducing items for individual scores from seven to four (measuring Collaboration, Roles, Patient/Family-centeredness, and Conflict Management) changed scale generalizability from .75 to .73. Performance assessment with two cases is associated with reasonable generalizability (.73). Students in newly-formed interprofessional teams show a learning curve after one patient encounter. Team scores from a two-station TOSCE demonstrate low generalizability whether the scale consisted of four (.53) or seven items (.55). Conclusion: The four-item Modified McMaster-Ottawa scale for assessing individual performance in interprofessional teams retains the generalizability and validity of the seven-item scale. Observation of students in teams interacting with two different patients provides reasonably reliable ratings for giving feedback. The four-item scale has potential for assessing individual student skills and the impact of IPE curricula in clinical practice settings

Evidence for a Monomeric Structure of Nonribosomal Peptide Synthetases

AbstractNonribosomal peptide synthetases (NRPS) are multimodular biocatalysts that bacteria and fungi use to assemble many complex peptides with broad biological activities. The same modular enzymatic assembly line principles are found in fatty acid synthases (FAS), polyketide synthases (PKS), and most recently in hybrid NRPS/PKS multienzymes. FAS as well as PKS are known to function as homodimeric enzyme complexes, raising the question of whether NRPS may also act as homodimers. To test this hypothesis, biophysical methods (size exclusion chromatography, analytical equilibrium ultracentrifugation, and chemical crosslinking) and biochemical methods (two-affinity-tag-system and complementation studies with enzymes being inactivated in different catalytic domains) were applied to NRPS subunits from the gramicidin S (GrsA-ATE), tyrocidine (TycB1-CAT and TycB2-3-AT.CATE), and enterobactin (EntF-CATTe) biosynthetic systems. These methods had revealed the dimeric structure of FAS and PKS previously, but all three NRPS systems investigated are functionally active as monomers