Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Standardization and Key Aspects of the Development of Whole Yeast Cell Vaccines

In the context of vaccine development, improving antigenic presentation is critical for the activation of specific immune responses and the success of immunization, in addition to selecting an appropriate target. In this sense, different strategies have been developed and improved. Among them is the use of yeast cells as vehicles for the delivery of recombinant antigens. These vaccines, named whole yeast vaccines (WYVs), can induce humoral and cellular immune responses, with the additional advantage of dispensing with the use of adjuvants due to the immunostimulatory properties of their cell wall components. However, there are some gaps in the methodologies for obtaining and validating recombinant strains and vaccine formulations. The standardization of these parameters is an important factor for WYVs approval by regulatory agencies and, consequently, their licensing. This review aimed to provide an overview of the main parameters to consider when developing a yeast-based vaccine, addressing some available tools, and highlighting the main variables that can influence the vaccine production process

Third-Generation Vaccines: Features of Nucleic Acid Vaccines and Strategies to Improve Their Efficiency

Gene immunization comprises mRNA and DNA vaccines, which stand out due to their simple design, maintenance, and high efficacy. Several studies indicate promising results in preclinical and clinical trials regarding immunization against ebola, human immunodeficiency virus (HIV), influenza, and human papillomavirus (HPV). The efficiency of nucleic acid vaccines has been highlighted in the fight against COVID-19 with unprecedented approval of their use in humans. However, their low intrinsic immunogenicity points to the need to use strategies capable of overcoming this characteristic and increasing the efficiency of vaccine campaigns. These strategies include the improvement of the epitopes’ presentation to the system via MHC, the evaluation of immunodominant epitopes with high coverage against emerging viral subtypes, the use of adjuvants that enhance immunogenicity, and the increase in the efficiency of vaccine transfection. In this review, we provide updates regarding some characteristics, construction, and improvement of such vaccines, especially about the production of synthetic multi-epitope genes, widely employed in the current gene-based vaccines

RNA Vaccines: Yeast as a Novel Antigen Vehicle

In the last decades, technological advances for RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle. Among the systems, yeasts emerge as a new approach, already employed to deliver protein antigens, with efficacy demonstrated through preclinical and clinical trials. β-glucans and mannans in their walls are responsible for the adjuvant property of this system. Yeast β-glucan capsules, microparticles, and nanoparticles can modulate immune responses and have a high capacity to carry nucleic acids, with bioavailability upon oral immunization and targeting to receptors present in antigen-presenting cells (APCs). In addition, yeasts are suitable vehicles for the protection and specific delivery of therapeutic vaccines based on RNAi. Compared to protein antigens, the use of yeast for DNA or RNA vaccine delivery is less established and has fewer studies, most of them in the preclinical phase. Here, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing the current challenges and prospects of this promising strategy

Understanding yeast shells: structure, properties and applications

Background and purpose: The employment of yeasts for biomedical purposes has become increasingly frequent for the delivery of prophylactic and therapeutic products. Its structural components, such as β-glucans, mannan, and chitin, can be explored as immunostimulators that show safety and low toxicity. Besides, this system minimizes antigen degradation after administration, facilitating the delivery to the target cells. Review approach: This review sought to present molecules derived from yeast, called yeast shells (YS), and their applications as carrier vehicles for drugs, proteins, and nucleic acids for immunotherapy purposes. Furthermore, due to the diversity of information regarding the production and immunostimulation of these compounds, a survey of the protocols and immune response profiles generated was presented. Key results: The use of YS has allowed the development of strategies that combine efficiency and effectiveness in antigen delivery. The capsular structure can be recognized and phagocytized by dendritic cells and macrophages. In addition, the combination with different molecules, such as nanoparticles or even additional adjuvants, improves the cargo loading, enhancing the system. Activation by specific immune pathways can also be achieved by different administration routes. Conclusion: Yeast derivatives combined in different ways can increase immunostimulation, enhancing the delivery of medicines and vaccine antigens. These aspects, combined with the simplicity of the production steps, make these strategies more accessible to be applied in the prevention and treatment of various diseases

RELATANDO E REFLETINDO SOBRE AS EXPERIÊNCIAS DO PIBID BIOLOGIA (IF GOIANO - CÂMPUS URUTAÍ) NO PERÍODO DE 2011 A 2013

O objetivo desse trabalho é relatar as experiências do PIBID Biologia (IF Goiano – Câmpus Urutaí), com destaque para as ações realizadas no Subprojeto de Ciências Biológicas; a visão dos supervisores bolsistas acerca da atuação e contribuição do programa na escola conveniada e na formação docente dos licenciandos; bem como a visão dos alunos bolsistas acerca da importância do subprojeto. Para a realização desse trabalho foi utilizada uma metodologia descritiva analítica, por meio da qual as atividades desenvolvidas foram relatadas de forma crítica e reflexiva. O Subprojeto de Ciências Biológicas (PIBID/IF Goiano – Câmpus Urutaí) atualmente conta com 15 alunos bolsistas e 3 professores supervisores do Colégio Estadual Professor Ivan Ferreira (CEPIF), Pires do Rio, GO. De modo geral, pode-se dizer que as atividades desenvolvidas têm atingindo positivamente não apenas os alunos bolsistas, mas também a melhoria de aspectos diversos ligados ao ensino de Biologia na escola conveniada. O PIBID-Biologia tem possibilitado aos seus bolsistas uma aproximação de sua futura atuação profissional

Advancing Immunotherapies for HPV-Related Cancers: Exploring Novel Vaccine Strategies and the Influence of Tumor Microenvironment

The understanding of the relationship between immunological responses and cancers, especially those related to HPV, has allowed for the study and development of therapeutic vaccines against these neoplasias. There is a growing number of studies about the composition and influence of the tumor microenvironment (TME) in the progression or establishment of the most varied types of cancer. Hence, it has been possible to structure immunotherapy approaches based on therapeutic vaccines that are even more specific and directed to components of TME and the immune response associated with tumors. Among these components are dendritic cells (DCs), which are the main professional antigen-presenting cells (APCs) already studied in therapy strategies for HPV-related cancers. On the other hand, tumor-associated macrophages are also potential targets since the profile present in tumor infiltrates, M1 or M2, influences the prognosis of some types of cancer. These two cell types can be targets for therapy or immunomodulation. In this context, our review aims to provide an overview of immunotherapy strategies for HPV-positive tumors, such as cervical and head and neck cancers, pointing to TME immune cells as promising targets for these approaches. This review also explores the potential of immunotherapy in cancer treatment, including checkpoint inhibitors, cytokine immunotherapies, immunotherapy vaccines, and cell therapies. Furthermore, it highlights the importance of understanding the TME and its effect on the design and achievement of immunotherapeutic methods

Anemia and anti-tuberculosis treatment outcome in persons with pulmonary tuberculosis: A multi-center prospective cohort study

Background: Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome. Methods: Patients ≥ 18 years old with culture-confirmed drug-susceptible pulmonary TB enrolled between 2015 and 2019 in a multi-center Brazilian cohort were followed for up to 24 months and classified according to anemia severity (mild, moderate, and severe), based on hemoglobin levels. A multinomial logistic regression model was employed to assess whether anemia was associated with unfavorable outcome (death, failure, loss to follow-up, regimen modification or relapse), compared to treatment success (cure or treatment completion). Results: Among 786 participants who met inclusion criteria, 441 (56 %) were anemic at baseline. Patients with moderate/severe anemia were more HIV-seropositive, as well as more symptomatic and had higher frequencies of unfavorable outcomes compared to the other groups. Moderate/severe anemia (adjusted OR [aOR]: 7.80, 95 %CI:1.34–45.4, p = 0.022) was associated with death independent of sex, age, BMI, HIV and glycemic status. Conclusion: Moderate/severe anemia prior to ATT was a significant risk factor for death. Such patients should be closely monitored given the high risk of unfavorable ATT outcomes

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data