Slow evolution toward "Super-Aggregation" of the oligomers formed through the swapping of RNase A N-Termini: a wish for amyloidosis?

Natively monomeric RNase A can oligomerize upon lyophilization from 40% acetic acid solutions or when it is heated at high concentrations in various solvents. In this way, it produces many dimeric or oligomeric conformers through the three-dimensional domain swapping (3D-DS) mechanism involving both RNase A N- or/and C-termini. Here, we found many of these oligomers evolving toward not negligible amounts of large derivatives after being stored for up to 15 months at 4 degrees C in phosphate buffer. We call these species super-aggregates (SAs). Notably, SAs do not originate from native RNase A monomer or from oligomers characterized by the exclusive presence of the C-terminus swapping of the enzyme subunits as well. Instead, the swapping of at least two subunits' N-termini is mandatory to produce them. Through immunoblotting, SAs are confirmed to derive from RNase A even if they retain only low ribonucleolytic activity. Then, their interaction registered with Thioflavin-T (ThT), in addition to TEM analyses, indicate SAs are large and circular but not "amyloid-like" derivatives. This confirms that RNase A acts as an "auto-chaperone", although it displays many amyloid-prone short segments, including the 16-22 loop included in its N-terminus. Therefore, we hypothesize the opening of RNase A N-terminus, and hence its oligomerization through 3D-DS, may represent a preliminary step favoring massive RNase A aggregation. Interestingly, this process is slow and requires low temperatures to limit the concomitant oligomers' dissociation to the native monomer. These data and the hypothesis proposed are discussed in the light of protein aggregation in general, and of possible future applications to contrast amyloidosis

Family planning: formal health care providers’ challenges in the district of Antananarivo Avaradrano

Background: Recorded contraceptive prevalence may not represent all the women using contraceptives. Nevertheless, it serves as a fundamental tool in decision-making at Ministry and international level. This study aims to determine the actual contraceptive prevalence and identify factors determining users’ positions about modern contraception and local services deliveries in the district of Antananarivo Avaradrano.Methods: A cross-sectional survey was conducted, where an interviewer-administered questionnaire has been used to collect data. Targeted female respondents aged 18-39 were asked about their contraceptive use, knowledge and information sources on family planning, perception of social support and perception on the local health care providers.Results: Contraceptive prevalence is underestimated. Moreover, it is higher among women aged 35 to 39 and those having two children or more, but lower among those who have reached university level of education. Women who are able to tell two benefits of family planning, informed by the community health agents (CHA), and deciding with their partners on contraception use are more likely to use contraceptives on a regular basis. Women complain on their poor relationship with health care providers and doubt about their real competence.Conclusions: This study demonstrates the evidence of an underestimation of contraceptive prevalence. The challenge is how to collect reliable data, thus recording systems have to be improved. Besides, government efforts in increasing contraceptive use ought to be targeted on adolescents and young people aged 20-25, the couple itself, health-care provider – woman relationship, and on the CHA’s activities.

A Influência das Características do Gestor no Sucesso da Gestão de Projetos

Project management has emerged among current management models and has become a factor to create a competitive advantage for companies in relation to their competitors. However, despite the increased interest in project management, little has been explored regarding managers who work with this type of management and their influence on determining the success or failure of the business. In this context, the present study aimed to analyze the influence of the project manager for small and large businesses in Santa Maria/RS in relation to the success of the businesses. This research is classified as quantitative and descriptive because it was conducted through a field study based on an accessible sample of small and large businesses in the city of Santa Maria. The main results showed that the managers of the surveyed companies were in the intermediate level of development with regard to the success of the projects as proposed by Newton (2011). This factor, however, does not significantly influence the success of projects managed by them.O gerenciamento de projetos tem se destacado entre os atuais modelos de administração e tem se transformado em um fator para criar vantagem competitiva nas empresas em relação aos seus concorrentes. Entretanto, apesar da grande abordagem em torno do gerenciamento de projetos em si, pouco se explora os gerentes que trabalham com esse tipo de gestão e as suas influências na determinação do sucesso ou fracasso do negócio da empresa. Nesse contexto, a presente pesquisa teve como objetivo analisar qual a influência do gestor de projetos de pequenas e grandes empresas de Santa Maria/RS no sucesso do seu negócio. Tendo em vista os processos metodológicos, a pesquisa classifica-se como quantitativa e descritiva quanto aos seus objetivos, sendo realizada através de um estudo de campo, com base em uma amostra por acessibilidade e pequenas e grandes empresas da cidade de Santa Maria. Como principais resultados evidenciou-se que os gestores das empresas pesquisadas estão em nível de desenvolvimento intermediário no que diz respeito aos pilares para o sucesso dos projetos proposto por Newton (2011), fator que não influencia, de maneira significativa, o sucesso dos projetos gerenciados por eles.DOI:10.5585/gep.v4i1.7

A Influência das Características do Gestor no Sucesso da Gestão de Projetos

Project management has emerged among current management models and has become a factor to create a competitive advantage for companies in relation to their competitors. However, despite the increased interest in project management, little has been explored regarding managers who work with this type of management and their influence on determining the success or failure of the business. In this context, the present study aimed to analyze the influence of the project manager for small and large businesses in Santa Maria/RS in relation to the success of the businesses. This research is classified as quantitative and descriptive because it was conducted through a field study based on an accessible sample of small and large businesses in the city of Santa Maria. The main results showed that the managers of the surveyed companies were in the intermediate level of development with regard to the success of the projects as proposed by Newton (2011). This factor, however, does not significantly influence the success of projects managed by them.O gerenciamento de projetos tem se destacado entre os atuais modelos de administração e tem se transformado em um fator para criar vantagem competitiva nas empresas em relação aos seus concorrentes. Entretanto, apesar da grande abordagem em torno do gerenciamento de projetos em si, pouco se explora os gerentes que trabalham com esse tipo de gestão e as suas influências na determinação do sucesso ou fracasso do negócio da empresa. Nesse contexto, a presente pesquisa teve como objetivo analisar qual a influência do gestor de projetos de pequenas e grandes empresas de Santa Maria/RS no sucesso do seu negócio. Tendo em vista os processos metodológicos, a pesquisa classifica-se como quantitativa e descritiva quanto aos seus objetivos, sendo realizada através de um estudo de campo, com base em uma amostra por acessibilidade e pequenas e grandes empresas da cidade de Santa Maria. Como principais resultados evidenciou-se que os gestores das empresas pesquisadas estão em nível de desenvolvimento intermediário no que diz respeito aos pilares para o sucesso dos projetos proposto por Newton (2011), fator que não influencia, de maneira significativa, o sucesso dos projetos gerenciados por eles.DOI:10.5585/gep.v4i1.7

Competition for cofactor-dependent DNA binding underlies Hox phenotypic suppression

The phenomenon of phenotypic suppression in Drosophila dictates that posterior Hox gene functions dominate over anterior ones. The underlying mechanisms have long remained a mystery. Mann and colleagues now dissect a mechanism of phenotypic suppression and find that posterior Hox AbdA can suppress activity of anterior Hox proteins only when they both bind to the same site. Suppression also depends on an AbdA-specific motif that is required for cooperative binding with the Exd cofactor. This suggests that phenotypic suppression depends on cofactor-dependent competition for DNA binding

Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax

The homothorax (hth) gene of Drosophila melanogaster is required for executing Hox functions, for head development, and for forming the proximodistal (PD) axis of the appendages. We show that alternative splicing of hth generates two types of protein isoforms, one that contains a DNA-binding homeodomain (HthFL) and one that does not contain a homeodomain (HDless). Both types of Hth isoforms include the evolutionarily conserved HM domain, which mediates a direct interaction with Extradenticle (Exd), another homeodomain protein. We show that although both HthFL and HDless isoforms of Hth can induce the nuclear localization of Exd, they carry out distinct sets of functions during development. Surprisingly, we find that many of hth’s functions, including PD patterning and most Hox-related activities, can be executed by the HDless isoforms. In contrast, antennal development shows an absolute dependency on the HthFL isoform. Thus, alternative splicing of hth results in the generation of multiple transcription factors that execute unique functions in vivo. We further demonstrate that the mouse ortholog of hth, Meis1, also encodes a HDless isoform, suggesting that homeodomain-less variants of this gene family are evolutionarily ancient

WHotLAMP: A simple, inexpensive, and sensitive molecular test for the detection of SARS-CoV-2 in saliva.

Despite the development of effective vaccines against SARS-CoV-2, epidemiological control of the virus is still challenging due to slow vaccine rollouts, incomplete vaccine protection to current and emerging variants, and unwillingness to get vaccinated. Therefore, frequent testing of individuals to identify early SARS-CoV-2 infections, contact-tracing and isolation strategies remain crucial to mitigate viral spread. Here, we describe WHotLAMP, a rapid molecular test to detect SARS-CoV-2 in saliva. WHotLAMP is simple to use, highly sensitive (~4 viral particles per microliter of saliva) and specific, as well as inexpensive, making it ideal for frequent screening. Moreover, WHotLAMP does not require toxic chemicals or specialized equipment and thus can be performed in point-of-care settings, and may also be adapted for resource-limited environments or home use. While applied here to SARS-CoV-2, WHotLAMP can be modified to detect other pathogens, making it adaptable for other diagnostic assays, including for use in future outbreaks