Peptoids advance multidisciplinary research and undergraduate education in parallel: Sequence effects on conformation and lipid interactions.

Peptoids are versatile peptidomimetic molecules with wide-ranging applications from drug discovery to materials science. An understanding of peptoid sequence features that contribute to both their three-dimensional structures and their interactions with lipids will expand functions of peptoids in varied fields. Furthermore, these topics capture the enthusiasm of undergraduate students who prepare and study diverse peptoids in laboratory coursework and/or in faculty led research. Here, we present the synthesis and study of 21 peptoids with varied functionality, including 19 tripeptoids and 2 longer oligomers. We observed differences in fluorescence spectral features for 10 of the tripeptoids that correlated with peptoid flexibility and relative positioning of chromophores. Interactions of representative peptoids with sonicated glycerophospholipid vesicles were also evaluated using fluorescence spectroscopy. We observed evidence of conformational changes effected by lipids for select peptoids. We also summarize our experiences engaging students in peptoid-based projects to advance both research and undergraduate educational objectives in parallel.

A Thermodynamic Description of the Adsorption of Simple Water-Soluble Peptoids to Silica.

The first report of a water-soluble peptoid adsorbed to silica monitored by second harmonic generation (SHG) at the liquid/solid interface is presented here. The molecular insights gained from these studies will inform the design and preparation of novel peptoid coatings. Simple 6- and 15-residue peptoids were dissolved in phosphate buffered saline and adsorbed to bare silica surfaces. Equilibrium binding constants and relative surface concentrations of adsorbed peptoids were determined from fits to the Langmuir model. Complementary fluorescence spectroscopy studies were used to quantify the maximum surface excess. Binding constants, determined here by SHG, were comparable to those previously reported for cationic proteins and small molecules. Enthalpies and free energies of adsorption were determined to elucidate thermodynamic driving forces. Circular dichroism spectra confirm that minimal conformational changes occur when peptoids are adsorbed to silica while pH studies indicate that electrostatic interactions impact adsorption.

Collective turns in jackdaw flocks: kinematics and information transfer.

The rapid, cohesive turns of bird flocks are one of the most vivid examples of collective behaviour in nature, and have attracted much research. Three-dimensional imaging techniques now allow us to characterize the kinematics of turning and their group-level consequences in precise detail. We measured the kinematics of flocks of wild jackdaws executing collective turns in two contexts: during transit to roosts and anti-predator mobbing. All flocks reduced their speed during turns, probably because of constraints on individual flight capability. Turn rates increased with the angle of the turn so that the time to complete turns remained constant. We also find that context may alter where turns are initiated in the flocks: for transit flocks in the absence of predators, initiators were located throughout the flocks, but for mobbing flocks with a fixed ground-based predator, they were always located at the front. Moreover, in some transit flocks, initiators were far apart from each other, potentially because of the existence of subgroups and variation in individual interaction ranges. Finally, we find that as the group size increased the information transfer speed initially increased, but rapidly saturated to a constant value. Our results highlight previously unrecognized complexity in turning kinematics and information transfer in social animals.

Tamoxifen with radiotherapy compared with Tamoxifen alone in elderly women with early-stage breast cancer treated with breast conserving surgery: A systematic review and meta-analysis.

BACKGROUND: Our aim was to assess the effect of adjuvant radiotherapy on recurrence and survival for elderly women (≥70) with early-stage hormone receptor-positive breast cancer treated with breast conserving surgery (BCS) and Tamoxifen. MATERIALS AND METHODS: MEDLINE, EMBASE, and Evidence-Based Medicine Reviews were systematically searched through August 12, 2016 for randomized controlled trials (RCTs) comparing radiotherapy to no radiotherapy and presenting outcomes for women ≥70years. Two investigators screened citations, abstracted results, and appraised studies using Cochrane Risk of Bias tool. Pooled risk ratios (RR) for breast, axillary, and distant recurrence, and overall survival were determined using weights from fixed-effects models. RESULTS: Four RCTs with low risk of bias were identified (2387 elderly women). Tamoxifen plus radiotherapy reduced breast recurrence compared to Tamoxifen alone from 60 to 10 (95% CI 6-20) per 1000 patients at 5years (RR 0.18, 95% CI 0.10-0.34; 4 trials, 2387 patients). This effect was maintained at 10years (RR 0.27, 95% CI 0.13-0.54; 2 trials, 891 patients). Radiotherapy minimally reduced axillary recurrence from 12 to 3 (95% CI 1-10) per 1000 at 5years (RR 0.28, 95% CI 0.10-0.81; 3 trials, 2287 patients). Radiotherapy did not affect distant recurrence (RR 1.49, 95% CI 0.87-2.54; 3 trials, 2287 patients) or overall survival (RR 0.98, 95% CI 0.79-1.22; 3 trials, 2287 patients). CONCLUSION: For elderly women (≥70), radiotherapy reduces the risk of breast and axillary recurrence, but does not impact distant recurrence or overall survival in early-stage breast cancer treated with BCS and Tamoxifen. The value of this risk reduction must be weighed by women and their physicians when considering the omission of adjuvant radiotherapy.

An 18-year experience in total colonic aganglionosis: from staged operations to primary laparoscopic endorectal pull-through.

BACKGROUND: Traditionally, total colonic aganglionosis (TCA) was managed with enterostomy +/- pull-through. Since 1998, primary laparoscopic endorectal pull-through (PLEP) was offered to patients with TCA in our unit. A retrospective study was conducted and early results reviewed. METHOD: Patient data were collected retrospectively. Before 1998, enterostomy followed by open Duhamel pull-through was performed. From 1998, patients were assessed to receive staged operation or PLEP. RESULTS: From June 1990 to May 2007, 10 patients (6 males) were treated. All presented in the neonatal period. Seven patients, with transition zone within proximal 15 cm of terminal ileum, had pull-through performed. Three had staged pull-through, whereas 4 had PLEP. Two had extensive small bowel involvement with high output stoma pending reconstruction. One had total intestinal aganglionosis and died. The 3 patients with staged pull-through had normal bowel habit without soiling (mean follow-up, 13 years). For PLEP, all procedures were accomplished laparoscopically without intraoperative complication (mean operative time, 6 hours 50 minutes). The mean bowel motion is 5x per day, but most were too young to evaluate continence (mean follow-up, 3.5 years). CONCLUSION: Primary laparoscopic endorectal pull-through is feasible in TCA with limited small bowel involvement and has the advantage of a single-stage operation, avoiding a stoma and its related complications.