A bivalent recombinant mycobacterium bovis BCG expressing the S1 subunit of the pertussis toxin induces a polyfunctional CD4 ⁺ T cell immune response

© 2019 Alex I. Kanno et al. Background. A recombinant BCG strain expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (rBCG-S1PT), previously constructed by our research group, demonstrated the ability to develop high protection in mouse models of pertussis challenge which correlated with the induction of a Th1 immune response pattern. The Th1 immune response induced by rBCG-S1PT treatment was also confirmed in the murine orthotopic bladder cancer model, in which the intravesical instillation of rBCG-S1PT resulted in an improved antitumor effect. Based on these observations, we hypothesize that the reengineering of the S1PT expression in BCG could increase the efficiency of the protective Th1 immune response in order to develop a new alternative of immunotherapy in bladder cancer treatment. Objectives. To construct rBCG strains expressing S1PT from extrachromosomal (rBCG-S1PT) and integrative vectors (rBCG-Sli), or their combination, generating the bivalent strain (rBCG-S1+S1i), and to evaluate the respective immunogenicity of rBCG strains in mice. Methods. Mycobacterial plasmids were constructed by cloning the s1pt gene under integrative and extrachromosomal vectors and used to transform BCG, individually or in combination. Antigen expression and localization were confirmed by Western blot. Mice were immunized with wild-type BCG or the rBCG strains, and cytokines quantification and flow cytometry analysis were performed in splenocytes culture stimulated with mycobacterial-specific proteins. Findings. S1PT expression was confirmed in all rBCG strains. The extrachromosomal vector directs S1PT to the cell wall-associated fraction, while the integrative vector directs its expression mainly to the intracellular fraction. Higher levels of IFN-γ were observed in the splenocytes culture from the group immunized with rBCG-S1i in comparison to BCG or rBCG-S1PT. rBCG-S1+S1i showed higher levels of CD4 + IFN-γ + and double-positive CD4 + IFN-γ + TNF-α + T cells. Conclusions. rBCG-S1+S1i was able to express the two forms of S1PT and elicited higher induction of polyfunctional CD4 + T cells, indicating enhanced immunogenicity and suggesting its use as immunotherapy for bladder cancer

Rodent models of heart failure: an updated review

Heart failure (HF) is one of the major health and economic burdens worldwide, and its prevalence is continuously increasing. The study of HF requires reliable animal models to study the chronic changes and pharmacologic interventions in myocardial structure and function and to follow its progression toward HF. Indeed, during the past 40 years, basic and translational scientists have used small animal models to understand the pathophysiology of HF and find more efficient ways of preventing and managing patients suffering from congestive HF (CHF). Each species and each animal model has advantages and disadvantages, and the choice of one model over another should take them into account for a good experimental design. The aim of this review is to describe and highlight the advantages and drawbacks of some commonly used HF rodents models, including both non-genetically and genetically engineered models, with a specific subchapter concerning diastolic HF models

‘Question Moments’: A Rolling Programme of Question Opportunities in Classroom Science

This article has been made available through the Brunel Open Access Publishing Fund.This naturalistic study integrates specific 'question moments' into lesson plans to increase pupils' classroom interactions. A range of teaching tools has explored students' ideas through opportunities to ask and write questions. Their oral and written outcomes provide data on individual and group misunderstandings. Changes to the schedule of lessons were introduced to discuss these questions and solve disparities. Flexible lesson planning over fourteen lessons across a four-week period of highschool chemistry accommodated students' contributions and increased student participation, promoted inquiring and individualised teaching, with each teaching strategy feeding forward into the next

Shedding light on the african enigma: In vitro testing of homo sapiens-helicobacter pylori coevolution

The continuous characterization of genome-wide diversity in population and case- cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the longstanding associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual humanand bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.Funds were guaranteed by the project “Advancing cancer research: from basic knowledge to application”; NORTE-01-0145-FEDER-000029; Projetos Estruturados de I & D & I, funded by Norte 2020-Programa Operacional Regional do Norte. i3S is financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Competitiveness and Internationalization Operational Programme (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

Terpenes as Potential Antimalarial Drugs

A fact which favors the increase in morbidity and mortality of malaria cases in the world is the resistance to chemotherapeutic agents that the parasite presents. Therefore, it is necessary to identify new potential targets specific to the parasite in order to be able to perform a rational planning. One target for the evaluation of potential antimalarial compounds is isoprenoid synthesis, which occurs via the 2-C-methyl-d -erythritol-4-phosphate pathway in Plasmodium falciparum. Several intermediaries and final products of this pathway were identified in the parasite and lead us to the conclusion that it is different from the vertebrate host. In this chapter, we describe the effect of some monoterpenes and sesquiterpenes on Plasmodium falciparum and Plasmodium berghei as potential antimalarial drugs

The influence of oral health conditions, socioeconomic status and home environment factors on schoolchildren's self-perception of quality of life

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: The objective this study was to investigate the influence of clinical conditions, socioeconomic status, home environment, subjective perceptions of parents and schoolchildren about general and oral health on schoolchildren's oral health-related quality of life (OHRQoL). Methods: A sample of 515 schoolchildren, aged 12 years was randomly selected by conglomerate analysis from public and private schools in the city of Juiz de Fora, Brazil. The schoolchildren were clinically examined for presence of caries lesions (DMFT and dmft index), dental trauma, enamel defects, periodontal status (presence/absence of bleeding), dental treatment and orthodontic treatment needs (DAI). The SiC index was calculated. The participants were asked to complete the Brazilian version of Child Perceptions Questionnaire (CPQ(11-14)) and a questionnaire about home environment. Questions were asked about the presence of general diseases and children's self-perception of their general and oral health status. In addition, a questionnaire was sent to their parents inquiring about their socioeconomic status (family income, parents' education level, home ownership) and perceptions about the general and oral health of their school-aged children. The chi-square test was used for comparisons between proportions. Poisson's regression was used for multivariate analysis with adjustment for variances. Results: Univariate analysis revealed that school type, monthly family income, mother's education, family structure, number of siblings, use of cigarettes, alcohol and drugs in the family, parents' perception of oral health of schoolchildren, schoolchildren's self perception their general and oral health, orthodontic treatment needs were significantly associated with poor OHRQoL (p < 0.001). After adjusting for potential confounders, variables were included in a Multivariate Poisson regression. It was found that the variables children's self perception of their oral health status, monthly family income, gender, orthodontic treatment need, mother's education, number of siblings, and household overcrowding showed a strong negative effect on oral health-related quality of life. Conclusions: It was concluded that the clinical, socioeconomic and home environment factors evaluated exerted a negative impact on the oral health-related quality of life of schoolchildren, demonstrating the importance of health managers addressing all these factors when planning oral health promotion interventions for this population.10Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2009/06081-7

Gamification, citizen science, and civic technologies: In search of the common good

In this paper, we discuss the importance of gameplay as a valuable tool in citizen sensing initiatives aimed at enabling creative collaboration and civic engagement. We present a review of selected citizen science and civic technologies’ projects highlighting an emerging culture of massive collaborative initiatives that make use of crowdsourcing, enabling users to voluntarily contribute their time, effort and resources towards scientific research and civic issues. Moreover, we discuss how these initiatives could benefit from the inclusion of gameplay in their interaction processes. For that matter, we present a gamified citizen sensing project we are devising for users to enter and retrieve information on commercially available food products which contain ingredients associated with an increased risk of cancer and other diseases. Through gameplay, we expect to crowdsource an open database of potentially unhealthy food products, raising awareness among consumers about the risks of certain artificial additives. Finally, we argue that the use of gamification processes can engage voluntary participation in initiatives aimed at citizenship – including those which demand complex and repetitive tasks for the collection of data – and call for a more ethical, critical, and meaningful use of these new potential technologies, and for greater awareness of our new civic responsibilities

Unravelling the structural variation of lizard osteoderms

Vertebrate skin is a remarkable organ that supports and protects the body. It consists of two layers, the epidermis and the underlying dermis. In some tetrapods, the dermis includes mineralised organs known as osteoderms (OD). Lizards, with over 7,000 species, show the greatest diversity in OD morphology and distribution, yet we barely understand what drives this diversity. This multiscale analysis of five species of lizards, whose lineages diverged ∼100–150 million years ago, compared the micro- and macrostructure, material properties, and bending rigidity of their ODs, and examined the underlying bones of the skull roof and jaw (including teeth when possible). Unsurprisingly, OD shape, taken alone, impacts bending rigidity, with the ODs of Corucia zebrata being most flexible and those of Timon lepidus being most rigid. Macroscopic variation is also reflected in microstructural diversity, with differences in tissue composition and arrangement. However, the properties of the core bony tissues, in both ODs and cranial bones, were found to be similar across taxa, although the hard, capping tissue on the ODs of Heloderma and Pseudopus had material properties similar to those of tooth enamel. The results offer evidence on the functional adaptations of cranial ODs, but questions remain regarding the factors driving their diversity

LOCUS (LOng Covid–Understanding Symptoms, events and use of services in Portugal): A three-component study protocol

Approximately 10% of patients experience symptoms of Post COVID-19 Condition (PCC) after a SARS-CoV-2 infection. Akin acute COVID-19, PCC may impact a multitude of organs and systems, such as the cardiovascular, respiratory, musculoskeletal, and neurological systems. The frequency and associated risk factors of PCC are still unclear among both community and hospital settings in individuals with a history of COVID-19. The LOCUS study was designed to clarify the PCC's burden and associated risk factors. LOCUS is a multi-component study that encompasses three complementary building blocks. The "Cardiovascular and respiratory events following COVID-19" component is set to estimate the incidence of cardiovascular and respiratory events after COVID-19 in eight Portuguese hospitals via electronic health records consultation. The "Physical and mental symptoms following COVID-19" component aims to address the community prevalence of self-reported PCC symptoms through a questionnaire-based approach. Finally, the "Treating and living with Post COVID-19 Condition" component will employ semi-structured interviews and focus groups to characterise reported experiences of using or working in healthcare and community services for the treatment of PCC symptoms. This multi-component study represents an innovative approach to exploring the health consequences of PCC. Its results are expected to provide a key contribution to the optimisation of healthcare services design.info:eu-repo/semantics/publishedVersio

A New Sugarcane Cystatin Strongly Binds to Dental Enamel and Reduces Erosion.

Cystatin B was recently identified as an acid-resistant protein in acquired enamel pellicle; it could therefore be included in oral products to protect against caries and erosion. However, human recombinant cystatin is very expensive, and alternatives to its use are necessary. Phytocystatins are reversible inhibitors of cysteine peptidases that are found naturally in plants. In plants, they have several biological and physiological functions, such as the regulation of endogenous processes, defense against pathogens, and response to abiotic stress. Previous studies performed by our research group have reported high inhibitory activity and potential agricultural and medical applications of several sugarcane cystatins, including CaneCPI-1, CaneCPI-2, CaneCPI-3, and CaneCPI-4. In the present study, we report the characterization of a novel sugarcane cystatin, named CaneCPI-5. This cystatin was efficiently expressed in Escherichia coli, and inhibitory assays demonstrated that it was a potent inhibitor of human cathepsins B, K, and L ( Ki = 6.87, 0.49, and 0.34 nM, respectively). The ability of CaneCPI-5 to bind to dental enamel was evaluated using atomic force microscopy. Its capacity to protect against initial enamel erosion was also tested in vitro via changes in surface hardness. CaneCPI-5 showed a very large force of interaction with enamel (e.g., compared with mucin and casein) and significantly reduced initial enamel erosion. These results suggest that the inclusion of CaneCPIs in dental products might confer protection against enamel erosion.This research was supported by the São Paulo Research Foundation (FAPESP) (CEPID-CBME #98/14138-2) and by the Royal Society (Newton Advanced Fellowship #NA140459). A.C.S. is a recipient of a scholarship from the National Council for Scientific and Technological Development (CNPq). M.C.M. received a grant from the Coordination for the Improvement of Higher Education Personnel (CAPES). V.T.P. received a grant from the FAPESP. F.H.-S. and M.A.R.B. were recipients of a productivity scholarship from the CNPq