The use of genes for performance enhancement: doping or therapy?

Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping

The development and implementation of a computer adaptive progress test across European countries

Longitudinal progress testing promotes self-directed deep learning across a full spectrum of knowledge, enabling early detection of underperformance and opportunities for remediation. Computer adaptive testing (CAT), where the difficulty of a test dynamically adjusts according to a test taker's ability, has benefits in a progress testing context, but significant resource and experience is required to develop appropriate test materials. This study describes how a transnational consortium from eight medical schools in five countries across Europe was formed to develop a computer adaptive progress test applicable across international curricula. 1,212 students from more than 40 nationalities took part in the study, of whom more than 70% were not native English speakers, though nearly all reported competence in English. A content map for an international assessment blueprint was agreed and a substantial bank of 1,127 English language progress test items was successfully calibrated after pilot testing to form the computer adaptive progress test (CA-PT) item bank. Results from the CA-PT pilot showed reliable convergence to stable estimates of ability, low standard errors of measurement and high test reliability for all participants. This study shows that an international collaborative consortium approach enables effective development of progress testing resources appropriate for computer adaptive testing, with potential for application across international borders and in populations where English is not the native language. Pooling resources internationally facilitates the comparison and development of appropriate assessment blueprints and the efficient generation of high-quality assessment items

Karyotype and genome size of Iberochondrostoma almacai (Teleostei, Cyprinidae) and comparison with the sister-species I.lusitanicum

This study aimed to define the karyotype of the recently described Iberian endemic Iberochondrostoma almacai, to revisit the previously documented chromosome polymorphisms of its sister species I.lusitanicum using C-, Ag-/CMA3 and RE-banding, and to compare the two species genome sizes. A 2n = 50 karyotype (with the exception of a triploid I.lusitanicum specimen) and a corresponding haploid chromosome formula of 7M:15SM:3A (FN = 94) were found. Multiple NORs were observed in both species (in two submetacentric chromosome pairs, one of them clearly homologous) and a higher intra and interpopulational variability was evidenced in I.lusitanicum. Flow cytometry measurements of nuclear DNA content showed some significant differences in genome size both between and within species: the genome of I. almacai was smaller than that of I.lusitanicum (mean values 2.61 and 2.93 pg, respectively), which presented a clear interpopulational variability (mean values ranging from 2.72 to 3.00 pg). These data allowed the distinction of both taxa and confirmed the existence of two well differentiated groups within I. lusitanicum: one that includes the populations from the right bank of the Tejo and Samarra drainages, and another that reunites the southern populations. The peculiar differences between the two species, presently listed as “Critically Endangered”, reinforced the importance of this study for future conservation plans

E-cadherin and cell adhesion: a role in architecture and function in the pancreatic islet

Background/Aims: The efficient secretion of insulin from beta-cells requires extensive intra-islet communication. The cell surface adhesion protein epithelial (E)-cadherin (ECAD) establishes and maintains epithelial tissues such as the islets of Langerhans. In this study, the role of ECAD in regulating insulin secretion from pseudoislets was investigated. Methods: The effect of an immuno-neutralising ECAD on gross morphology, cytosolic calcium signalling, direct cell-to-cell communication and insulin secretion was assessed by fura-2 microfluorimetry, Lucifer Yellow dye injection and insulin ELISA in an insulin-secreting model system. Results: Antibody blockade of ECAD reduces glucose-evoked changes in [Ca2+](i) and insulin secretion. Neutralisation of ECAD causes a breakdown in the glucose-stimulated synchronicity of calcium oscillations between discrete regions within the pseudoislet, and the transfer of dye from an individual cell within a cell cluster is attenuated in the absence of ECAD ligation, demonstrating that gap junction communication is disrupted. The functional consequence of neutralising ECAD is a significant reduction in insulin secretion. Conclusion: Cell adhesion via ECAD has distinct roles in the regulation of intercellular communication between beta-cells within islets, with potential repercussions for insulin secretion. Copyright (C) 2007 S. Karger AG, Basel

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

CORROSÃO DE AÇOS INOXIDÁVEIS AUSTENÍTICOS EM SAIS FUNDIDOS TERNÁRIOS DE CÁLCIO

O armazenamento de energia térmica (TES) é um fator chave para melhorar a eficiência e a despachabilidade dos diferentes sistemas energéticos, devido a um melhor ajustamento entre a procura e a oferta de energia, e ao permitir o desenvolvimento e a implementação de energias renováveis. Um exemplo claro é o TES em instalações de concentração de energia solar (CSP), onde o excesso de energia solar durante o período de luz solar é armazenado para ser utilizado durante os períodos em que a energia solar é necessária, mas não está disponível. Os sais fundidos têm sido amplamente utilizados como fluidos de transferência de calor (HTF) e para TES em instalações CSP. Uma das características fundamentais dos sais fundidos no que diz respeito à sua utilização como HTF e TES é a sua compatibilidade com os materiais de construção. Por esta razão, este trabalho apresenta a resistência à corrosão de dois aços inoxidáveis austeníticos AISI 316L e AISI 321H em contacto com sal ternário fundido com cálcio. Ambos os aços inoxidáveis demonstraram ter velocidades de corrosão aceitáveis para as centrais CSP. Entre os aços austeníticos estudados, o AISI 316L apresenta a menor velocidade de corrosão

Comparison of formula and number-right scoring in undergraduate medical training: a Rasch model analysis

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Progress testing is an assessment tool used to periodically assess all students at the end-of-curriculum level. Because students cannot know everything, it is important that they recognize their lack of knowledge. For that reason, the formula-scoring method has usually been used. However, where partial knowledge needs to be taken into account, the number-right scoring method is used. Research comparing both methods has yielded conflicting results. As far as we know, in all these studies, Classical Test Theory or Generalizability Theory was used to analyze the data. In contrast to these studies, we will explore the use of the Rasch model to compare both methods. Methods A 2 × 2 crossover design was used in a study where 298 students from four medical schools participated. A sample of 200 previously used questions from the progress tests was selected. The data were analyzed using the Rasch model, which provides fit parameters, reliability coefficients, and response option analysis. Results The fit parameters were in the optimal interval ranging from 0.50 to 1.50, and the means were around 1.00. The person and item reliability coefficients were higher in the number-right condition than in the formula-scoring condition. The response option analysis showed that the majority of dysfunctional items emerged in the formula-scoring condition. Conclusions The findings of this study support the use of number-right scoring over formula scoring. Rasch model analyses showed that tests with number-right scoring have better psychometric properties than formula scoring. However, choosing the appropriate scoring method should depend not only on psychometric properties but also on self-directed test-taking strategies and metacognitive skills

Borrelia valaisiana resist complement-mediated killing independently of the recruitment of immune regulators and inactivation of complement components

Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae