HoxPred: automated classification of Hox proteins using combinations of generalised profiles

<p>Abstract</p> <p>Background</p> <p>Correct identification of individual Hox proteins is an essential basis for their study in diverse research fields. Common methods to classify Hox proteins focus on the homeodomain that characterise homeobox transcription factors. Classification is hampered by the high conservation of this short domain. Phylogenetic tree reconstruction is a widely used but time-consuming classification method.</p> <p>Results</p> <p>We have developed an automated procedure, HoxPred, that classifies Hox proteins in their groups of homology. The method relies on a discriminant analysis that classifies Hox proteins according to their scores for a combination of protein generalised profiles. 54 generalised profiles dedicated to each Hox homology group were produced <it>de novo </it>from a curated dataset of vertebrate Hox proteins. Several classification methods were investigated to select the most accurate discriminant functions. These functions were then incorporated into the HoxPred program.</p> <p>Conclusion</p> <p>HoxPred shows a mean accuracy of 97%. Predictions on the recently-sequenced stickleback fish proteome identified 44 Hox proteins, including HoxC1a only found so far in zebrafish. Using the Uniprot databank, we demonstrate that HoxPred can efficiently contribute to large-scale automatic annotation of Hox proteins into their paralogous groups. As orthologous group predictions show a higher risk of misclassification, they should be corroborated by additional supporting evidence. HoxPred is accessible via SOAP and Web interface <url>http://cege.vub.ac.be/hoxpred/</url>. Complete datasets, results and source code are available at the same site.</p

Using concept mapping to identify policy options and interventions towards people-centred health care services : a multi stakeholders perspective

Background: People-centred health care (PCC) services are identified by the WHO as important building blocks towards universal health coverage. In 2016 the WHO formulated a comprehensive framework on integrated PCC services based on an international expert consultation. Yet, expert opinions may fail to recognize the needs of all health system stakeholders. Therefore, a consultation method that includes the health workforce and laypersons, can be instrumental to elaborate this framework more in-depth. This research sought to identify participants' perspectives on policy options and interventions to achieve people-centred health care services from a multi stakeholder perspective. Methods: Study participants, both laypersons and health professionals, were recruited in Belgium. A total of 53 participants engaged in one of the seven concept mapping workshops. In this workshop the concept mapping methodology developed by Trochim, a highly structured qualitative group method for brainstorming and idea sharing, was used to generate and structure participants perspectives on what is needed to achieve PCC services. The method was validated using the WHO framework. Results: The seven workshops together resulted in 452 different statements that were structured in a framework forming 35 clusters and four overarching domains. The four domains with their most prominent clusters were: (1) governance & policy with intersectoral health policies and affordable health for all; (2) health workforce with excellent communication skills, appreciation of health literacy challenges and respectful attitude based on cultural self-awareness; (3) integrated health services with a greater emphasis on prevention, health promotion and the availability of health education and (4) patient, person and community empowerment and participation with support for informal care, promotion of a healthy lifestyle and contextualised health education. Additionally, this study generated ideas that fitted into every single approach described in the WHO framework. Discussion and conclusion: This study shows that in order to achieve PCC a participative approach involving all stakeholders at all levels is needed. The concept mapping process is one of these approaches that brings together diverse stakeholders and foments their egalitarian and respectful participation. The framework that resulted from this study can inform future debate regarding planning, implementation and monitoring of PCC

Nematicidal activity of Bacillus thuringiensis isolates

L'activité nématicide de mélanges de spores et d'inclusions cristallines de trois isolats de #Bacillus thuringiensis envers les juvéniles et les adultes de #Caenorhabditis elegans est étudiée. La toxicité est déterminée en ajoutant 50 micro l d'une suspension de 200 à 400 juvéniles et adultes de "C. elegans$. La mortalité des nématodes est observée après 8 heures d'incubation ; aucune augmentation significative du pourcentage de mortalité n'est observée après 24 heures d'incubation. Ce pourcentage varie d'environ 50 à 60 % lorsque les tests sont réalisés avec de l'eau distillée et il augmente légèrement (moins de 10 %) si les tests sont effectués en milieu axénique. La toxicité varie selon les isolats. Un minimum de 10 8 particules/ml est nécessaire pour provoquer un effet létal supérieur à 3%. L'activité nématicide n'est observée qu'avec des mélanges de spores et d'inclusions critallines provenant de cultures âgées d'au moins 2 jours et constituées d'environ 50 % de cellules végétatives - contenant souvent une spore - et d'environ 50 % d'une mixture de spores et d'inclusions critallines. Le chauffage à 75 °C ou plus pendant 24 heures ou un autoclavage à 120°C pendant 20 minutes détruit l'activité nématicide des trois isolats. Des différences de stabilité de l'activité nématicide sont observées entre les trois isolats. Celle-ci ne diminue pas pour deux isolats maintenus à 28°C durant quinze jours, mais elle diminue pour le troisième s'il est stocké sept jours à 28°C. De même, l'activité nématicide de deux des isolats n'est pas modifiée après plusieurs congélations à -20°C ou -70°C suivies de décongélations, mais elle diminue pour le troisième isolat. Les variations du pH des mélanges de particules entraînent des variations dans la stabilité des activités nématicides des trois isolats. Ces résultats pourraient indiquer la présence de toxines différentes. (Résumé d'auteur

Needs and Resources of People With Type 2 Diabetes in Peri-urban Cochabamba, Bolivia: a People-centred Perspective

Background: The rising prevalence of type 2 diabetes results in a worldwide public healthcare crisis, especially in low- and middle-income countries (LMICs) with unprepared and overburdened health systems mainly focused on infectious diseases and maternal and child health. Studies regarding type 2 diabetes in LMICs describe specific interventions ignoring a comprehensive analysis of the local factors people see influential to their health. This study aims to meet this research gap by exploring what people with type 2 diabetes in Bolivia need to maintain or improve their health, how important they perceive those identified needs and to what extent these needs are met. Methods: From March until May 2019, 33 persons with type 2 diabetes from three periurban municipalities of the department of Cochabamba participated in this study. The concept mapping methodology by Trochim, a highly structured qualitative brainstorming method, was used to generate and structure a broad range of perspectives on what the participants consider instrumental for their health. Results: The brainstorming resulted in 156 original statements condensed into 72 conceptually different needs and resources, structured under nine conceptual clusters and four action domains. These domains illustrated with vital needs were: (1) self-management with use of plants and the possibility to measure sugar levels periodically; (2) healthcare providers with the need to trust and receive an uniform diagnose and treatment plan; (3) health system with opportune access to care and (4) community with community participation in health and safety, including removal of stray dogs. Conclusions: This study identifies mostly contextual factors like low literacy levels, linguistic problems in care, the need to articulate people's worldview and traditional use of natural remedies with the Bolivian health system and the lack of expertise on type 2 diabetes by primary health care providers. Understanding the needs and structuring them in different areas wherein action is required serves as a foundation for the planning and evaluation of an integrated people centred care program for people with type 2 diabetes. This participative method serves as a tool to implement the often theoretical concept of integrated people centred health care in health policy and program development

A non-tree-based comprehensive study of metazoan Hox and ParaHox genes prompts new insights into their origin and evolution

Hox and the closely-related ParaHox genes, which emerged prior to the divergence between cnidarians and bilaterians, are the most well-known members of the ancient genetic toolkit that controls embryonic development across all metazoans. Fundamental questions relative to their origin and evolutionary relationships remain however unresolved. We investigate here the evolution of metazoan Hox and ParaHox genes using the HoxPred program that allows the identification of Hox genes without the need of phylogenetic tree reconstructions.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Targeting tauopathy with engineered tau-degrading intrabodies

BACKGROUND: The accumulation of pathological tau is the main component of neurofibrillary tangles and other tau aggregates in several neurodegenerative diseases, referred to as tauopathies. Recently, immunotherapeutic approaches targeting tau have been demonstrated to be beneficial in decreasing tauopathy in animal models. We previously found that passive immunotherapy with anti-tau antibody to human tau or expression of an anti-tau secreted single-chain variable fragment (scFv) in the central nervous system of a mouse model of tauopathy decreased but did not remove all tau-associated pathology. Although these and other studies demonstrate that conventional immunotherapeutic approaches targeting tau can influence tau pathogenesis, the majority of pathological tau remains in the cytosol of cells, not typically accessible to an extracellular antibody. Therefore, we reasoned targeting intracellular tau might be more efficacious in preventing or decreasing tauopathy. METHODS: By utilizing our anti-tau scFv, we generated anti-tau intrabodies for the expression in the cytosol of neurons. To enhance the degradation capacity of conventional intrabodies, we engineered chimeric anti-tau intrabodies fused to ubiquitin harboring distinct mutations that shuttle intracellular tau for either the proteasome or lysosomal mediated degradation. To evaluate the efficacy in delaying or eliminating tauopathy, we expressed our tau degrading intrabodies or controls in human tau transgenic mice by adeno-associated virus prior to overt tau pathology and after tau deposition. RESULTS: Our results demonstrate, the expression of chimeric anti-tau intrabodies significantly reduce tau protein levels in primary neuronal cultures expression human tau relative to a non-modified anti-tau intrabody. We found the expression of engineered tau-degrading intrabodies destined for proteasomal-mediated degradation are more effective in delaying or eliminating tauopathy than a conventional intrabody in aged human tau transgenic mice. CONCLUSION: This study, harnesses the strength of intrabodies that are amendable for targeting specific domains or modifications with the cell-intrinsic mechanisms that regulate protein degradation providing a new immunotherapeutic approach with potentially improved efficacy

Effect of nematicidal Bacillus thuringiensis strains on free-living nematodes : 2. Ultrastructural analysis of the intoxication process in Caenorhabditis elegans

La microscopie électronique par transmission a été utilisée pour décrire l'intoxication de #Caenorhabditis elegans se nourrissant sur des spores/cristaux de #Bacillus thuringiensis. La toxine agit directement sur l'intestin où elle affecte initialement l'anneau de quatre cellules le plus antérieur. En 12 heures, le volume de ces cellules diminue considérablement, les microvillosités régressent lentement, de nombreux organites cellulaires subissent des changements spectaculaires pour être finalement détruits. Il n'a pas été observé de rupture de la membrane cellulaire apicale. Les tissus autres qu'intestinaux n'apparaissent pas affectés. Cette étude révèle des différences ultrastructurales considérables entre le mode d'action des toxines nématicides et celui des cristaux insecticides émanant les uns et les autres de #Bacillus thuringiensis$. (Résumé d'auteur

TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

Significance Alzheimer’s disease (AD) is the most common cause of dementia and is a major public health problem for which there is currently no disease-modifying treatment. There is an urgent need for greater understanding of the molecular mechanisms underlying neurodegeneration in patients to create better therapeutic options. Recently, genetic studies uncovered novel AD risk variants in the microglial receptor, triggering receptor expressed on myeloid cells 2 (TREM2). Previous studies suggested that loss of TREM2 function worsens amyloid-β (Aβ) plaque-related toxicity. In contrast, we observe TREM2 deficiency mitigates neuroinflammation and protects against brain atrophy in the context of tau pathology. These findings indicate dual roles for TREM2 and microglia in the context of amyloid versus tau pathology, which are important to consider for potential treatments targeting TREM2.</jats:p

Effect of a nematicidal Bacillus thuringiensis strain on free- living nematodes : 3. Characterization of the intoxication process

La toxicité de #Bacillus thuringiensis est fonction de la température. L'incubation de #Caenorhabditis elegans avec des souches de #B. thuringiensis à 16, 20 et 25°C montre que la toxicité décroît en même temps que la température. A 16°C, la toxicité disparaît complètement, tandis qu'elle atteint son maximum à 25°C. La toxicité, fonction du pH, diminue significativement lorsque les nématodes sont mis en incubation dans des bases faibles (NH4Cl, chloroquine, acridine orange, rouge de méthyle, rouge neutre). A partir de ces résultats, il est possible d'avancer l'hypothèse que l'agent nématicide pénètre à l'intérieur des cellules intestinales, ce qui constitue une différence notable avec les toxines des souches insecticides de #B. thuringiensis lesquelles agissent au niveau de la membrane en brosse. Bien que l'absence de toxine purifiée ne permette pas l'élucidation définitive de son mode d'action, les résultats exposés dans cette troisième, et dernière, partie de la série de publications traitant du sujet, apportent une indication convaincante du fait que les souches nématicides de #B. thuringiensis$ ne peuvent tenir les mêmes promesses que les souches insecticides en tant qu'agent de contrôle biologique. (Résumé d'auteur