αvβ3 and α5β1 integrin-specific ligands: From tumor angiogenesis inhibitors to vascularization promoters in regenerative medicine?

Integrins are cell adhesion receptors predominantly important during normal and tumor angiogenesis. A sequence present on several extracellular matrix proteins composed of Arg-Gly-Asp (RGD) has attracted attention due to its role in cell adhesion mediated by integrins. The development of ligands that can bind to integrins involved in tumor angiogenesis and brake disease progression has resulted in new investigational drug entities reaching the clinical trial phase in humans. The use of integrin-specific ligands can be useful for the vascularization of regenerative medicine constructs, which remains a major limitation for translation into clinical practice. In order to enhance vascularization, immobilization of integrin-specific RGD peptidomimetics within constructs is a recommended approach, due to their high specificity and selectivity towards certain desired integrins. This review endeavours to address the potential of peptidomimetic-coated biomaterials as vascular network promoters for regenerative medicine purposes. Clinical studies involving molecules tracking active integrins in cancer angiogenesis and reasons for their failure are also addressed.Prémios Santa Casa Neurociências - Prize Melo e Castro for Spinal Cord Injury Research; Portuguese Foundation for Science and Technology [Doctoral fellowship (PD/BDE/127835/2016) to L. A. Rocha; IF Development Grant to A. J. Salgado; national funds through grant TUBITAK/0007/2014]. This article has been developed under the scope of the projects NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER); This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

Reproductive Failure in UK Harbour Porpoises Phocoena phocoena : Legacy of Pollutant Exposure?

This research was supported by a Marie Curie International Outgoing Fellowship within the Seventh European Community Framework Programme (Project Cetacean-stressors, PIOF-GA-2010-276145 to PDJ and SM). Additional funding was provided through the Agreement on the Conservation of Small Cetaceans of the Baltic, North East Atlantic, Irish and North Seas (ASCOBANS) (Grants SSFA/2008 and SSFA / ASCOBANS / 2010 / 5 to SM). Analysis of Scottish reproductive and teeth samples was funded by the EC-funded BIOCET project (BIOaccumulation of persistent organic pollutants in small CETaceans in European waters: transport pathways and impact on reproduction, grant EVK3-2000-00027 to GJP), and Marine Scotland (GJP). Samples examined in this research were collected under the collaborative Cetacean Strandings Investigation Programme (http://ukstrandings.org/), which is funded by the Department for Environment, Food and Rural Affairs (Defra) and the UK’s Devolved Administrations in Scotland and Wales (http://sciencesearch.defra.gov.uk/Defaul​t.aspx?Menu=Menu&Module=More&Location=No​ne&Completed=0&ProjectID=15331) (grants to PDJ, RD). UK Defra also funded the chemical analysis under a service-level agreement with the Centre for Environment, Fisheries and Aquaculture Science (grants to RJL, JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Electronic Structure of the ID Conductor K0.3MoO3 studied using resonant inelastic x-ray scattering and soft x-ray emission spectroscopy

The electronic structure of the quasi-one dimensional conductor K{sub 0.3}MoO{sub 3} has been measured using high resolution resonant inelastic x-ray scattering and x-ray absorption spectroscopy. The data is compared to that from the related two dimensional insulator {alpha}-MoO{sub 3}. Scattering features are observed from both oxides that are explained in terms of the band momentum selectivity of the scattering process, allowing a comparison of the scattering data to recent band structure calculations

The development of path integration: combining estimations of distance and heading

Efficient daily navigation is underpinned by path integration, the mechanism by which we use self-movement information to update our position in space. This process is well-understood in adulthood, but there has been relatively little study of path integration in childhood, leading to an underrepresentation in accounts of navigational development. Previous research has shown that calculation of distance and heading both tend to be less accurate in children as they are in adults, although there have been no studies of the combined calculation of distance and heading that typifies naturalistic path integration. In the present study 5-year-olds and 7-year-olds took part in a triangle-completion task, where they were required to return to the startpoint of a multi-element path using only idiothetic information. Performance was compared to a sample of adult participants, who were found to be more accurate than children on measures of landing error, heading error, and distance error. 7-year-olds were significantly more accurate than 5-year-olds on measures of landing error and heading error, although the difference between groups was much smaller for distance error. All measures were reliably correlated with age, demonstrating a clear development of path integration abilities within the age range tested. Taken together, these data make a strong case for the inclusion of path integration within developmental models of spatial navigational processing

A new short uncemented, proximally fixed anatomic femoral implant with a prominent lateral flare: design rationals and study design of an international clinical trial

<p>Abstract</p> <p>Background</p> <p>Anatomic short femoral prostheses with a prominent lateral flare have the potential to reduce stress-shielding in the femur through a more physiological stress distribution to the proximal femur. We present the design rationale of a new short uncemented, proximally fixed anatomic femoral implant and the study design of a prospective multi-centre trial to collect long-term patient outcome and radiographic follow up data.</p> <p>Methods</p> <p>A prospective surveillance study (trial registry NCT00208555) in four European centres (UK, Italy, Spain and Germany) with a follow up period of 15 years will be executed. The recruitment target is 200 subjects, patients between the ages of 18 and 70 admitted for primary cementless unilateral THA will be included. The primary objective is to evaluate the five-year survivorship of the new cementless short stem. The secondary objectives of this investigation are to evaluate the long term survivorship and the clinical performance of the implant, the impact on the subjects health related Quality of Life and the affect of the prosthesis on bone mineral density. Peri- and postoperative complications will be registered. Clinical and radiographic evaluation of prosthesis positioning will be done post-operatively and at 3, 6, 12, 24, 60, 120 and 180 months follow up.</p> <p>Discussion</p> <p>Shortening of the distal stem can maximise bone and soft tissue conservation. New stem types have been designed to improve the limitations of traditional implants in primary THA. A new, uncemented femoral short stem is introduced in this paper. A long-term follow up study has been designed to verify stable fixation and to research into the clinical outcome. The results of this trial will be presented as soon as they become available.</p

Leadership and charisma: a desire that cannot speak its name?

Leadership has proved impossible to define, despite decades of research and a huge number of publications. This article explores managers’ accounts of leadership, and shows that they find it difficult to talk about the topic, offering brief definitions but very little narrative. That which was said/sayable provides insights into what was unsaid/ unsayable. Queer theory facilitates exploration of that which is difficult to talk about, and applying it to the managers’ talk allows articulation of their lay theory of leadership. This is that leaders evoke a homoerotic desire in followers such that followers are seduced into achieving organizational goals. The leader’s body, however, is absent from the scene of seduction, so organizational heteronormativity remains unchallenged. The article concludes by arguing that queer and critical leadership theorists together could turn leadership into a reverse discourse and towards a politics of pleasure at work

BaVS3_3 probed by V L edge X-ray absorption spectroscopy

Polarization dependent vanadium L edge X-ray absorption spectra of BaVS$_3$ single crystals are measured in the four phases of the compound. The difference between signals with the polarization \textbf{E}$\perp$\textbf{c} and \textbf{E}$\parallel$\textbf{c} (linear dichroism) changes with temperature. Besides increasing intensity of one of the maxima, a new structure appears in the pre-edge region below the metal-insulator transition. More careful examination brings to light that the changes start already with pretransitional charge density wave fluctuations. Simple symmetry analysis suggests that the effect is related to rearrangements in $E_{g}$ and $A_{1g}$ states, and is compatible with the formation of four inequivalent V sites along the V-S chain.Comment: 6 pages, 6 figure