Identification of a new European rabbit IgA with a serine-rich hinge region

<div><p>In mammals, the most striking IgA system belongs to Lagomorpha. Indeed, 14 IgA subclasses have been identified in European rabbits, 11 of which are expressed. In contrast, most other mammals have only one IgA, or in the case of hominoids, two IgA subclasses. Characteristic features of the mammalian IgA subclasses are the length and amino acid sequence of their hinge regions, which are often rich in Pro, Ser and Thr residues and may also carry Cys residues. Here, we describe a new IgA that was expressed in New Zealand White domestic rabbits of <i>IGHV</i>a1 allotype. This IgA has an extended hinge region containing an intriguing stretch of nine consecutive Ser residues and no Pro or Thr residues, a motif exclusive to this new rabbit IgA. Considering the amino acid properties, this hinge motif may present some advantage over the common IgA hinge by affording novel functional capabilities. We also sequenced for the first time the IgA14 CH2 and CH3 domains and showed that IgA14 and IgA3 are expressed.</p></div

‘Welcome to the Machine!’ Resisting isomorphic, masculinised corporatisation of Higher Education through feminist scholarship

This paper discusses the synthesised findings from two interdisciplinary, feminist studies conducted under the auspices of the non-corporate nexus, the Women’s Academic Network at Bournemouth University, UK, of which the main author is a co-convenor and co-founder. These qualitative studies focus on academic women’s experiences of managing careers in the work culture of corporate Institutions of Higher Education (HEI) in a modern UK university. The background to this work draws from a body of international research into the slower career progression rates of women academics in comparison to male counterparts and gendered barriers the former encounter. While there has encouragement within Higher Education bodies across the EU to balance out the current gendered inequities within academia, our findings indicate that these are woven into the institutional fabric of enacted daily academic practices serving to disadvantage women scholars

Incidencia de las metodologías de enseñanza en los estudiantes universitarios

The general objective of the research was to describe the incidence of teaching methodologies in university students. It was developed from the quantitative paradigm, also framed from a documentary-bibliographic design, through the inquiry, collection and critical documentary analysis and bibliographic reference, based on the methodical, rigorous and deep exploration of various documentary sources such as scientific research, articles, refereed works, theses, among others. Describing the findings found, allowing the development of the theoretical body in relation to the subject of study. It was concluded that the training process at the university level must be rethought and open to the changes that are being generated as a result of technology, globalization and the social context; hence the importance of having teaching methodologies that allow the generation of knowledge and meaningful learning allowing the development of critical thinking and the acquisition of skills for future professionals graduating from universities. El objetivo general de la investigación fue describir la incidencia de las metodologías de enseñanza en los estudiantes universitarios. Se desarrolló desde el paradigma cuantitativo, además se enmarcó desde un diseño documental-bibliográfico, mediante la indagación, recolección y análisis crítico documental y referencial bibliográfico, basándose en la exploración metódica, rigurosa y profunda de diversas fuentes documentales tales como investigaciones científicas, artículos, trabajos arbitrados, tesis, entre otros. Describiendo los hallazgos encontrados, permitiendo desarrollar el cuerpo teórico en relación al tema de estudio. Se concluyó que, el proceso de formación a nivel universitario debe estar replanteada y abierta a los cambios que se están generando producto de la tecnología, la globalización y el contexto social; de allí la importancia de contar con metodologías de enseñanza que permitan la generación de conocimiento y aprendizaje significativo permitiendo un desarrollo del pensamiento crítico y adquisición de competencias para los futuros profesionales que egresaran de las universidades.

Normativas del MINEDUC para estudiantes con superdotación o altas capacidades tema no explorado

En la actual investigación se analizan los estilos de aprendizaje en estudiantes superdotados del Ecuador, con la finalidad de conocer la preferencia de estilo predominante y articular una orientación sobre el abordaje escolar a desarrollarse con pertinencia de promover una educación inclusiva y de calidad, teniendo en cuenta las normativas vigentes.Para la búsqueda bibliográfica se revisaron libros de texto y revistas biomédicas nacionales e internacionales, así como protocolos, guías y programas existentes en el mundo sobre la atención integral a los adolescentes, concluyéndose  que urge fortalecer la perspectiva del aprendizaje centrada en el estudiante, estopermitirá que, mediante la investigación e indagación, el estudiante genere un aprendizaje en razón de sus exigencias, perspectivas, en posibilidad de crecer en consonancia a los múltiples retos globales.

Rabbit IgA Hinges That Resist IgA1 Protease Action Provide Options for Improved IgA-Based Therapeutic Agents

Immunoglobulin A provides a major line of defence against pathogens and plays a key role in the maintenance of the commensal microbiota in the intestinal tract. Having been shown to be more effective at tumour cell killing than IgG and strongly active against pathogens present in the mucosae, IgA antibodies have been attracting significant attention in recent years for use as therapeutic antibodies. To improve their therapeutic potential, bioengineered IgA forms with increased serum half-life and neutralizing abilities have been developed but the IgA hinge, which impacts susceptibility to bacterial proteases and ability to bridge between target and effector cells, has not yet been explored. The European rabbit has 15 IgA subclasses with exclusive hinge region motifs and varying lengths, constituting a unique model to evaluate the functional capabilities offered by incorporation of longer IgA hinges into immunoglobulins. Hinge regions from rabbit IgAs, featuring different lengths and sequences, were inserted into human IgA1 heavy chain to substitute the IgA1 hinge. These hinges did not appear to affect antigen binding nor the ability of the engineered chimeric IgA1 to bind and trigger FcαRI, as detected by IgA-mediated cell agglutination and release of superoxide by neutrophils. All rabbit hinge-human IgA1 hybrids were resistant to Clostridrum ramosum IgA protease enzyme digestion, as predicted by the lack of the cleavage site in the rabbit hinges. Some IgA1s featuring long rabbit hinges were cleaved by Neisseria meningitidis IgA1 protease cleavage type 1 or 2 enzymes, despite the lack of the predicted cleavage sites. More interestingly, the hybrid featuring the rabbit IgA15 hinge was not affected by any of the IgA proteases. The IgA15 hinge is longer than that found in human IgA1 and is composed by a unique motif with a stretch of nine consecutive Ser residues. These characteristics allow the preservation of a long hinge, with associated ability to bridge distantly spaced antigens and provide higher avidity binding, while remaining resistant to IgA protease degradation. The data suggest that the rabbit Cα15 hinge represents an interesting alternative hinge sequence for therapeutic human IgA antibodies that remains resistant to proteolytic cleavage

Advancing the theory and practice of impact assessment: Setting the research agenda

Impact assessment has been in place for over 40 years and is now practised in some form in all but two of the world's nations. In this paper we reflect on the state of the art of impact assessment theory and practice, focusing on six well-established forms: EIA, SEA, policy assessment, SIA, HIA and sustainability assessment. We note that although the fundamentals of impact assessment have their roots in the US National Environmental Policy Act 1969 (NEPA) each branch of the field is distinct in also drawing on other theoretical and conceptual bases that in turn shape the prevailing discourse in each case, generating increasing degrees of specialisation within each sub-field. Against this backdrop, we consider the strengths and weaknesses of collective impact assessment practice, concluding that although there are substantial strengths, the plethora of specialist branches is generating a somewhat confusing picture and lack of clarity regarding how the pieces of the impact assessment jigsaw puzzle fit together. We use this review to suggest an overarching research agenda that will enable impact assessment to evolve in line with changing expectations for what it should deliver

The revised Humpty Dumpty Fall Scale: An update to improve tool performance and predictive validity

The purpose of this study was to identify potential modifications to the Humpty Dumpty Fall Scale (HDFS) in order to enhance the accuracy of fall prediction in the pediatric population, thus contributing to the safest possible environment for the hospitalized child. A secondary analysis of data collected by Gonzalez et al. (2020), including a total of 2428 patients, was conducted for this study. Multiple logistic regression was used to examine the relationship between each parameter of the HDFS (e.g., age, gender, diagnosis, cognitive impairments, environmental factors, response to surgery/sedation/anesthesia, and medication usage) and the outcome of fall status. After reviewing associations between HDFS parameters and fall risk, neither gender nor medication use were found to be associated with fall risk. These two parameters were removed from the scoring algorithms, and the HDFS was modified to a minimum score of 5 and maximum score of 20, with a score of 12 or above indicative of high risk of fall. The modified scale demonstrated a sensitivity of 84% and specificity of 57%. These revisions are anticipated to help support clinical practice and improve fall prevention, thus supporting a safer pediatric environment for the hospitalized child. •The Humpty Dumpty Fall Scale is widely used to identify hospitalized children at risk of fall.•After analysis, several parameters were removed from the scale, and the scoring was updated.•The modified scale demonstrated a sensitivity of 84% and specificity of 57%.•These changes support clinical practice and improve fall prevention.•The updated tool is anticipated to provide a safer pediatric environment for the hospitalized child

Characterization of natural amino acid variation for each residue identified under positive selection in mammal IgA.

a<p>IgA1 Bur numbering.</p>b<p>amino acid characteristics: H- Hydrophilic, HY- Hydrophobic, +- positive, –negative, n-neutral.</p

Phylogenetic tests of positive selection in mammals.

a<p>Codons identified by more than one ML method are underlined.</p>b<p>ps = proportion of the sites under selection, ωs = estimated dN/dS of the sites under selection in M8.</p>c<p>Positively Selected Codons: only the codons identified by at least two of the ML methods were considered to be positively selected codons.</p

Residues encoded by PSC in the three-dimensional structure of human IgA1 and their relationship to sites of biological interest.

<p>A, Model of human IgA1 (PBD ID 1iga) with residues encoded by PSC highlighted. The light chains are colored green and the heavy chains colored yellow. Positively selected positions are represented by red dots (selected in mammals), black dots (selected in primates and mammals) or blue dots (selected in primates). B to F, Human IgA1-Fc (PDB ID 1OW0) with residues critical for FcαRI interaction (B), pIgR interaction (C), SSL7 interaction (D), streptococci IgA binding proteins interaction (E), and <i>H. influenzae</i> type 2 IgA1 protease interaction (F) highlighted in cyan, orange, pink, purple and grey respectively. Positively selected positions are represented as in panel A. Differences between the Fc structures in A and B-F reflect the fact that the model of intact IgA1 in A is based on low resolution X-ray and neutron scattering modeled based on the X-ray crystal structure of IgG Fc (the closest structure available at the time of modeling), while B-F show an X-ray crystal structure of human IgA1-Fc solved as part of a complex with FcαRI (not shown).</p