Gestures and Adaptive Niches: an Evolutionary Perspective on Co-speech Gestures

This proposal presents an evolutionary analysis of three types of co-speech gestures: symbolic emblems, indexical pointing gestures and iconic representational gesticulations. Synthesizing insights from a range of published sources in gestural studies, general linguistics and sign language linguistics, primate studies and analyses of biological evolution, these gestures are analyzed as evolved traits adapted to particular niches or roles within broader systems. Niche boundaries are comprised of an element’s distinct properties and functions, routes of learning and transmission and degrees of innateness and evolvability within populations. Rather than elements distributed along a flat productive-analytical continuum or as stages along diachronic pathways, these gestural traits are analyzed in terms of adaptive peaks and valleys with a landscape representing the broader system comprising human gesture and language. The same evolutionary processes are used to analyze gestures in speaking populations and the linguistic traits derived from gestures in signing populations. This approach offers new ways of approaching proposed linguistic universals and long-standing issues such as listability in sign languages, while offering a formal approach to gestures

Wound-healing studies in transgenic and knockout mice

Injury to the skin initiates a cascade of events including inflammation, new tissue formation, and tissue remodeling, that finally lead to at least partial reconstruction of the original tissue. Historically, animal models of repair have taught us much about how this repair process is orchestrated and, over recent years, the use of genetically modified mice has helped define the roles of many key molecules. Aside from conventional knockout technology, many ingenious approaches have been adopted, allowing researchers to circumvent such problems as embryonic lethality, or to affect gene function in a tissue-or temporal-specific manner. Together, these studies provide us with a growing source of information describing, to date, the in vivo function of nearly 100 proteins in the context of wound repair. This article focuses on the studies in which genetically modified mouse models have helped elucidate the roles that many soluble mediators play during wound repair, encompassing the fibroblast growth factor (FGF) and transforming growth factor-β (TGF-β) families and also data on cytokines and chemokines. Finally, we include a table summarizing all of the currently published data in this rapidly growing field. For a regularly updated web archive of studies, we have constructed a Compendium of Published Wound Healing Studies on Genetically Modified Mice which is available at http://icbxs.ethz.ch/members/grose/woundtransgenic/home.htm

742-4 Radial Artery Graft: Angiographic Follow-up

Interest in the use of the radial artery (RA) as a coronary bypass graft has increased. Attention to harvesting and use of perioperative calcium channel inhibitors have ameliorated problems with spasm noted in earlier studies. Since 1993, 72 patients (pts) underwent grafting using a free RA from the non-dominant forearm. Re-angiography was performed in 24 pts to date and is the subject of this study. Pts ranged from 39–79 years (mean 55.5); all had 2 or 3 vessel disease and an average of 3 grafts/pt were constructed (range 2–4). Left internal thoracic artery (L1TA) was used in all cases except 1. The RA was a single graft in 19 including 2 to the LAD system, 12 to the circumflex system and 5 to the RCA. The RA-was sequential in 5 cases. Of the 24 pts catheterized an average of 9 weeks post-op 24/24 RA's were patent: 1 (sequential) RA had a mid-graft stenosis. There was no spasm seen in any RA. RA distal diameters (2.6mm) were well matched to the recipient vessel (RV) (2.2mm). The ratio RV/graft diameter was 0.83 for the radial artery similar to the ratio for the L1TA (0.90).ConclusionThe RA is a viable coronary conduit, easily harvested and has excellent early patency rates

Simple and objective prediction of survival in patients with lung cancer: staging the host systemic inflammatory response

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer

A 3D in vitro model of the human breast duct:A method to unravel myoepithelial-luminal interactions in the progression of breast cancer

Abstract Background 3D modelling fulfils a critical role in research, allowing for complex cell behaviour and interactions to be studied in physiomimetic conditions. With tissue banks becoming established for a number of cancers, researchers now have access to primary patient cells, providing the perfect building blocks to recreate and interrogate intricate cellular systems in the laboratory. The ducts of the human breast are composed of an inner layer of luminal cells supported by an outer layer of myoepithelial cells. In early-stage ductal carcinoma in situ, cancerous luminal cells are confined to the ductal space by an intact myoepithelial layer. Understanding the relationship between myoepithelial and luminal cells in the development of cancer is critical for the development of new therapies and prognostic markers. This requires the generation of new models that allows for the manipulation of these two cell types in a physiological setting. Methods Using access to the Breast Cancer Now Tissue Bank, we isolated pure populations of myoepithelial and luminal cells from human reduction mammoplasty specimens and placed them into 2D culture. These cells were infected with lentiviral particles encoding either fluorescent proteins, to facilitate cell tracking, or an inducible human epidermal growth factor receptor 2 (HER2) expression construct. Myoepithelial and luminal cells were then recombined in collagen gels, and the resulting cellular structures were analysed by confocal microscopy. Results Myoepithelial and luminal cells isolated from reduction mammoplasty specimens can be grown separately in 2D culture and retain their differentiated state. When recombined in collagen gels, these cells reform into physiologically reflective bilayer structures. Inducible expression of HER2 in the luminal compartment, once the bilayer has formed, leads to robust luminal filling, recapitulating ductal carcinoma in situ, and can be blocked with anti-HER2 therapies. Conclusions This model allows for the interaction between myoepithelial and luminal cells to be investigated in an in-vitro environment and paves the way to study early events in breast cancer development with the potential to act as a powerful drug discovery platform

Workshops for subject-specific teachers’ training: A case study for teaching cancer biology

Teachers’ training in higher education institutions widely serves general purposes. However, recent dialogues and research highlight the importance of teachers’ deep understanding of the material being taught and the ways students think about the content as critical components of great teaching. We explored the novelty of providing a one-day workshop entitled, ‘Effective strategies for teaching cancer biology’. The Biochemical Society supported the event and marketed it throughout the UK – not with any targeted level of university teaching experience and attendees therefore ranged from those who had never taught to those at the level of Senior Fellow of the Higher Education Academy. The day included various short talks, the sharing of good practice and the opportunity to experience a demonstration lesson as a student. Twelve out of thirteen who provided feedback had not received previous subject-specific teacher-training. Half of the attendees gave feedback with the highest score out of five, having found the event ‘very valuable’. This experience suggests that subject-specific training may be beneficial and applicable to other subject areas

In silico targeting of colony-stimulating factor-1 receptor: delineating immunotherapy in cancer

Aim: Delineate structure-based inhibition of colony-stimulating factor-1 receptor (CSF1R) by small molecule CSF1R inhibitors in clinical development for target identification and potential lead optimization in cancer therapeutics since CSF1R is a novel predictive biomarker for immunotherapy in cancer. Methods: Compounds were in silico modelled by induced fit docking protocol in a molecular operating environment (MOE, MOE.v.2015). The 3-dimensional (3D) X-ray crystallized structure of CSF1R kinase (Protein Databank, ID 4R7H) was obtained from Research Collaboratory for Structural Bioinformatics (RSCB) Protein Databank. The 3D conformers of edicotinib, DCC-3014, ARRY-382, BLZ-945, chiauranib, dovitinib, and sorafenib were obtained from PubChem Database. These structures were modelled in Amber10:EHT molecular force field, and quick prep application was used to correct and optimize the structures for missing residues, H-counts, termini capping, and alternates. The binding site was defined within the vicinity of the co-crystallized ligand of CSF1R kinase. The compounds were docked by the triangular matcher placement method and ranked by the London dG scoring function. The docked poses were further refined by the induced fit method. The pose with the lowest binding score (ΔG) was used to model the ligand interaction profile in Discovery Studio Visualizer v17.2. The co-crystallized ligand was docked in its apo conformation, and root-mean-square deviation was computed to validate the docking protocol. Results: All 7 CSF1R inhibitors interact with residue Met637 exhibiting selectivity except for edicotinib. The inhibitors maintain CSF1R in an auto-inhibitory conformation by interacting with Asp797 of the Asp-Phe-Gly (DFG) motif and/or hindering the conserved salt bridge formed between Glu633 and Lys616 thus stabilizing the activation loop, or interacting with tryptophan residue (Trp550) in the juxtamembrane domain. DCC-3014, ARRY-382, BLZ-945, and sorafenib bind with the lowest binding energy with CSF1R kinase. Conclusions: Pyrimidines are potent inhibitors that interact with CSF1R residues. DCC-3014 and ARRY-382 exhibit exceptional pharmaceutical potential exhibiting great structural stability and affinity

The atmospheric effects of stratospheric aircraft: A fourth program report

This document presents the fourth report from the Atmospheric Effects of Stratospheric Aircraft (AESA) component of NASA's High-Speed Research Program (HSRP). Market and technology considerations continue to provide an impetus for high-speed civil transport research. A recent AESA interim assessment report and a review of that report have shown that considerable uncertainty still exists about the possible impact of aircraft on the atmosphere. The AESA has been designed to develop the body of scientific knowledge necessary for the evaluation of the impact of stratospheric aircraft on the atmosphere. The first Program report presented the basic objectives and plans for AESA. This fourth report comes after the interim assessment and sets forth directions for the 1995 assessment at the end of AESA Phase 1. It also sets forth the goals and directions for AESA Phase 2, as reported at the 1994 Atmospheric Effects of Aviation Project (AEAP) annual meeting held in June. The focus of the Phase 2 effort is to obtain the best possible closure on the outstanding problems identified in the interim assessment and NASA/NRC review. Topics discussed in this report include how high-speed civil transports (HSCT) might affect stratospheric ozone, emissions scenarios and databases to assess potential atmospheric effects from HSCT's, calculated results from 2-D zonal mean models using emissions data, engine trace constituent measurements

Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis

Loss of FGFRs results in skin abnormalities due to activation of keratinocytes and epidermal T cells