Oral Treatment with Iododiflunisal Delays Hippocampal Amyloid-β Formation in a Transgenic Mouse Model of Alzheimer's Disease: A Longitudinal in vivo Molecular Imaging Study

Transthyretin (TTR) is a tetrameric, amyloid-β (Aβ)-binding protein, which reduces Aβ toxicity. The TTR/Aβ interaction can be enhanced by a series of small molecules that stabilize its tetrameric form. Hence, TTR stabilizers might act as disease-modifying drugs in Alzheimer's disease. Objective: We monitored the therapeutic efficacy of two TTR stabilizers, iododiflunisal (IDIF), which acts as small-molecule chaperone of the TTR/Aβ interaction, and tolcapone, which does not behave as a small-molecule chaperone, in an animal model of Alzheimer's disease using positron emission tomography (PET). Methods: Female mice (AβPPswe/PS1A246E/TTR+/-) were divided into 3 groups (n=7 per group): IDIF-treated, tolcapone-treated, and non-treated. The oral treatment (100mg/Kg/day) was started at 5 months of age. Treatment efficacy assessment was based on changes in longitudinal deposition of Aβ in the hippocampus (HIP) and the cortex (CTX) and determined using PET-[18F]florbetaben. Immunohistochemical analysis was performed at age=14 months. Results: Standard uptake values relative to the cerebellum (SUVr) of [18F]florbetaben in CTX and HIP of non-treated animals progressively increased from age=5 to 11 months and stabilized afterwards. In contrast, [18F]florbetaben uptake in HIP of IDIF-treated animals remained constant between ages=5 and 11 months and significantly increased at 14 months. In the tolcapone-treated group, SUVr progressively increased with time, but at lower rate than in the non-treated group. No significant treatment effect was observed in CTX. Results from immunohistochemistry matched the in vivo data at age=14 months. Conclusion: Our work provides encouraging preliminary results on the ability of small-molecule chaperones to ameliorate Aβ deposition in certain brain regions

Survival Factors for Subcontractors in Economic Downturns

This paper analyzes key issues facing subcontractors in the context of a severe economic crisis, aiming to detect the factors that are critical for the survival of the subcontractors. While previous research efforts have analyzed factors related to subcontractor performance in regular financial conditions, there remains only sparse knowledge of how subcontractors are to survive when economic conditions become dire as they have in recent times in the Spanish construction market. In this research, in-depth interviews with managers of relevant Spanish subcontracting companies were carried out, resulting in the identification of eight factors for subcontractor survival: project delivery method, demand, financial capital, relationship assets, managerial assets, human assets, legal framework, and geographic scope. The project delivery method used by the owner and also by the main contractor is mainly based on price. As a result, the subcontractors bids get lower, making them unsustainable in the long run. Furthermore, subcontractors do not get financial support from banks easily in order to cover their additional financial costs. These facts push subcontractors to get a guarantee of payment by the main contractor, while subcontracting companies may even ask for payments in advance. Subcontractors also seek long-term relationships with the contractor. These trusting relations are very often a prerequisite to qualify and bid for contracts. Subcontractors have to continuously improve, plan ahead and adapt quickly to the new environment. Therefore, subcontractors must remain flexible and maintain a lean hierarchical organization. Doing so makes it is easier for subcontractors to compete in both their native markets, as well as abroad. To this end, the most successful subcontractors have become international during the expansion phase of the economic cycle; many of them went abroad with the help of a contractor from their home country.This research was partially supported by Santander Universidades (Becas Iberoamerica Jovenes Profesionales e Investigadores 2012) that funded a visitorship for Ricardo Oviedo-Haito. The authors are also indebted to all the participants in this research, as well as to Dr. Debra Westall and Dr. Nathaniel Sobin for revising the manuscript. Finally, the valuable commentaries and suggestions of three anonymous reviewers are also highly appreciated.Oviedo-Haito, R.; Jiménez Ayala, J.; Cardoso, F.; Pellicer Armiñana, E. (2014). Survival Factors for Subcontractors in Economic Downturns. Journal of Construction Engineering and Management. 140(3):40130501-40130510. doi:10.1061/(ASCE)CO.1943-7862.0000811S4013050140130510140

GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm.

In vertebrates, GATA2 is a master regulator of hematopoiesis and is expressed throughout embryo development and in adult life. Although the essential role of GATA2 in mouse hematopoiesis is well established, its involvement during early human hematopoietic development is not clear. By combining time-controlled overexpression of GATA2 with genetic knockout experiments, we found that GATA2, at the mesoderm specification stage, promotes the generation of hemogenic endothelial progenitors and their further differentiation to hematopoietic progenitor cells, and negatively regulates cardiac differentiation. Surprisingly, genome-wide transcriptional and chromatin immunoprecipitation analysis showed that GATA2 bound to regulatory regions, and repressed the expression of cardiac development-related genes. Moreover, genes important for hematopoietic differentiation were upregulated by GATA2 in a mostly indirect manner. Collectively, our data reveal a hitherto unrecognized role of GATA2 as a repressor of cardiac fates, and highlight the importance of coordinating the specification and repression of alternative cell fates.Ramón y Cajal Program, Spanish Ministry of Economy, Industry, and Competitiveness, Spanish Cancer Association, FERO, Instituto de Salud Carlos III, European Social Fund, MINECO, PERIS Program of the Generalitat de Catalunya, Obra Social la Caixa-Fundacion Josep Carreras, Spanish Institute of Health Carlos III, Wellcome Trust, MRC, CRUK, NIH-NIDD

The Azorean Biodiversity Portal: an internet database for regional biodiversity outreach

Copyright © 2010 The Natural History Museum.There is a growing interest in academia to provide biodiversity data to both the scientific community and the public. We present an internet database of the terrestrial lichens, bryophytes, vascular plants, molluscs, arthropods, vertebrates and coastal invertebrates of the Azores archipelago (Portugal, North Atlantic): the Azorean Biodiversity Portal (ABP, http://www.azoresbioportal.angra.uac.pt/). This is a unique resource for fundamental research in systematics, biodiversity, education and conservation management. The ABP was based on a regional species database (ATLANTIS), comprised of grid-based spatial incidence information for c. 5000 species. Most of the data rely on a comprehensive literature survey (dating back to the 19th century) as well as unpublished records from recent field surveys in the Azores. The ABP disseminates the ATLANTIS database to the public, allowing universal, unrestricted access to much of its data. Complementarily, the ABP includes additional information of interest to the general public (e.g. literature on Macaronesian biodiversity) together with images from collections and/or live specimens for many species. In this contribution we explain the implementation of a regional biodiversity database, its architecture, achievements and outcomes, strengths and limitations; we further include a number of suggestions in order to implement similar initiatives

International collaborative follow - up investigation of graduating high school students’ understandings of the nature of scientific inquiry: is progress Being made?

Understandings of the nature of scientific inquiry (NOSI), as opposed to engaging students in inquiry learning experiences, are included in science education reform documents around the world. However, little is known about what students have learned about NOSI during their pre-college school years. The purpose of this large-scale follow-up international project (i.e. 32 countries and regions, spanning six continents and including 3917 students for the high school sample) was to collect data on what exiting high school students have learned about NOSI. Additionally, the study investigated changes in 12th grade students’ NOSI understandings compared to seventh grade (i.e. 20 countries and regions) students’ understandings from a prior investigation [Lederman et al. (2019). An international collaborative investigation of beginning seventh grade students’ understandings of scientific inquiry: Establishing a baseline. Journal of Research in Science Teaching, 56(4), 486–515. https://doi.org/10.1002/tea.21512]. This study documents and discusses graduating high school students’ understandings and compares their understandings to seventh grade students’ understandings of the same aspects of scientific inquiry for each country. It is important to note that collecting data from each of the 130+ countries globally was not feasible. Similarly, it was not possible to collect data from every region of each country. A concerted effort was made, however, to provide a relatively representative picture of each country and the world

Quality Assurance Driving Factors as Antecedents of Knowledge Management: a Stakeholder-Focussed Perspective in Higher Education

Similar to many other types of organisations, the successful development of higher education institutions generally depends on proactive multi-stakeholder management strategy. As a social responsibility of universities, quality assurance (QA) of higher education is already an established research domain. However, the issues that serve as driving factors in higher education’s quality are acknowledged in this vast knowledge stream in a dispersed way. An objective of this paper is to provide a quick snapshot of the major QA driving factors in higher education. Another objective here is to discuss the significance of these existing QA driving factors in higher education as prospective antecedents of knowledge management among the key stakeholders in the higher education sector and beyond. An inductive constructivist approach is followed to review the relevant QA driving factors from the extant scholarly views. A number of relevant factors are précised from the literature that would be instrumental to uphold quality in higher education. The discussion demonstrates that these factors are also significant to transfer and share knowledge between the key stakeholders not only for universities, but also for businesses, governments and other organisational stakeholders. The paper proposes a framework of the QA drivers’ application for meaningful knowledge transfer between diverse stakeholders and clarifies the framework’s managerial implications. This conceptual framework specifies different scenarios and perspectives of QA drivers’ application in the global education sector. The academic novelty is based on the inductive approach applied in the paper. QA practitioners will be able to follow these factors as steering phenomena to effectively assure quality, in relation to their multi-stakeholder relationships in higher education and beyond

Precision restoration: a necessary approach to foster forest recovery in the 21st century

We thank S. Tabik, E. Guirado, and Garnata Drone SL for fruitful debates about the application of remote sensing and artificial intelligence in restoration. E. McKeown looked over the English version of the manuscript. Original drawings were made by J. D. Guerrero. This work was supported by projects RESISTE (P18-RT-1927) from the Consejeria de Economia, Conocimiento, y Universidad from the Junta de Andalucia, and AVA201601.19 (NUTERA-DE I), DETECTOR (A-RNM-256-UGR18), and AVA2019.004 (NUTERA-DE II), cofinanced (80%) by the FEDER Program. F.M.-R. acknowledges the support of the Agreement 4580 between OTRI-UGR and the city council of La Zubia. We thank an anonymous reviewer for helpful comments that improved the manuscript.Forest restoration is currently a primary objective in environmental management policies at a global scale, to the extent that impressive initiatives and commitments have been launched to plant billions of trees. However, resources are limited and the success of any restoration effort should be maximized. Thus, restoration programs should seek to guarantee that what is planted today will become an adult tree in the future, a simple fact that, however, usually receives little attention. Here, we advocate for the need to focus restoration efforts on an individual plant level to increase establishment success while reducing negative side effects by using an approach that we term “precision forest restoration” (PFR). The objective of PFR will be to ensure that planted seedlings or sowed seeds will become adult trees with the appropriate landscape configuration to create functional and self-regulating forest ecosystems while reducing the negative impacts of traditional massive reforestation actions. PFR can take advantage of ecological knowledge together with technologies and methodologies from the landscape scale to the individual- plant scale, and from the more traditional, low-tech approaches to the latest high-tech ones. PFR may be more expensive at the level of individual plants, but will be more cost-effective in the long term if it allows for the creation of resilient forests able to providemultiple ecosystemservices. PFR was not feasible a few years ago due to the high cost and low precision of the available technologies, but it is currently an alternative that might reformulate a wide spectrum of ecosystem restoration activities.Junta de Andalucia P18-RT-1927European Commission AVA201601.19 A-RNM-256-UGR18 AVA2019.004OTRI-UGR 4580city council of La Zubia 458

The prevalence of Giardia infection in dogs and cats, a systematic review and meta-analysis of prevalence studies from stool samples

Giardia has a wide range of host species and is a common cause of diarrhoeal disease in humans and animals. Companion animals are able to transmit a range of zoonotic diseases to their owners including giardiasis, but the size of this risk is not well known. The aim of this study was to analyse giardiasis prevalence rates in dogs and cats worldwide using a systematic search approach. Meta-analysis enabled to describe associations between Giardia prevalence and various confounding factors. Pooled prevalence rates were 15.2% (95% CI 13.8-16.7%) for dogs and 12% (95% CI 9.2-15.3%) for cats. However, there was very high heterogeneity between studies. Meta-regression showed that the diagnostic method used had a major impact on reported prevalence with studies using ELISA, IFA and PCR reporting prevalence rates between 2.6 and 3.7 times greater than studies using microscopy. Conditional negative binomial regression found that symptomatic animals had higher prevalence rates ratios (PRR) than asymptomatic animals 1.61 (95% CI 1.33-1.94) in dogs and 1.94 (95% CI 1.47-2.56) in cats. Giardia was much more prevalent in young animals. For cats >6 months, PRR=0.47 (0.42-0.53) and in dogs of the same age group PRR=0.36 (0.32-0.41). Additionally, dogs kept as pets were less likely to be positive (PRR=0.56 (0.41-0.77)) but any difference in cats was not significant. Faecal excretion of Giardia is common in dogs and slightly less so in cats. However, the exact rates depend on the diagnostic method used, the age and origin of the animal. What risk such endemic colonisation poses to human health is still unclear as it will depend not only on prevalence rates but also on what assemblages are excreted and how people interact with their pets