Continent-island boundary and environment-shaped evolution in the marine amphipod Ampithoe marcuzzii complex (Crustacea: Eumalacostraca: Ampithoidae).

Marine amphipods are crustaceans that lack a larval phase and consequently have low dispersion rates. Despite that, these crustaceans present a remarkable ability to be transported by rafting on natural floating substrata, especially macroalgae, where they find shelter, food and a mating ground. The species Ampithoe marcuzzii is widely distributed throughout the western Atlantic Ocean. Here, it was used as a model to study seascape genomics and phylogeography in invertebrates with low dispersion capacities. We anticipated that the lineages would present isolation-by-distance patterns. However, surface currents and other abiotic variables could facilitate connectivity among distant sites. Based on mitochondrial and nuclear genes, SNPs, and environmental associations, we observed the presence of a species complex within A. marcuzzii, separating mainland and insular populations. Each species showed an independent evolutionary history, with a strong latitudinal population structure and evidence of isolation-by-distance and isolation-by-environment, characterizing the 'continent' species. Historical expansion and environmental variables were observed associated with the southeastern population, and ecological niche modeling corroborated the region as a paleorefuge. Conversely, populations from 'islands' presented complicated evolutionary histories, with closer localities genetically isolated and distant localities connected. These findings indicate that insular populations with low dispersion capacity might be more susceptible to spatial connectivity by floating substrata and to changes in surface currents. In contrast, mainland populations might be more vulnerable to local climate changes due to lack of gene flow.

Venomous Noodles: The Evolution of Toxins in Nemertea through Positive Selection and Gene Duplication.

Some, probably most and perhaps all, members of the phylum Nemertea are poisonous, documented so far from marine and benthic specimens. Although the toxicity of these animals has been long known, systematic studies on the characterization of toxins, mechanisms of toxicity, and toxin evolution for this group are scarce. Here, we present the first investigation of the molecular evolution of toxins in Nemertea. Using a proteo-transcriptomic approach, we described toxins in the body and poisonous mucus of the pilidiophoran Lineus sanguineus and the hoplonemertean Nemertopsis pamelaroeae. Using these new and publicly available transcriptomes, we investigated the molecular evolution of six selected toxin gene families. In addition, we also characterized in silico the toxin genes found in the interstitial hoplonemertean, Ototyphlonemertes erneba, a meiofaunal taxa. We successfully identified over 200 toxin transcripts in each of these species. Evidence of positive selection and gene duplication was observed in all investigated toxin genes. We hypothesized that the increased rates of gene duplications observed for Pilidiophora could be involved with the expansion of toxin genes. Studies concerning the natural history of Nemertea are still needed to understand the evolution of their toxins. Nevertheless, our results show evolutionary mechanisms similar to other venomous groups.

Comparing iDNA from mosquitoes and flies to survey mammals in a semi-controlled Neotropical area.

Ingested-derived DNA (iDNA) from insects represents a powerful tool for assessing vertebrate diversity because insects are easy to sample, have a diverse diet and are widely distributed. Because of these advantages, the use of iDNA for detecting mammals has gained increasing attention. Here we aimed to compare the effectiveness of mosquitoes and flies to detect mammals with a small sampling effort in a semi-controlled area, a zoo that houses native and non-native species. We compared mosquitoes and flies regarding the number of mammal species detected, the amount of mammal sequence reads recovered, and the flight distance range for detecting mammals. We also verified if the combination of two mini-barcodes (12SrRNA and 16SrRNA) would perform better than either mini-barcode alone to inform local mammal biodiversity from iDNA. To capture mosquitoes and flies, we distributed insect traps in eight sampling points during 5 days. We identified 43 Operational Taxonomic Units from 10 orders, from the iDNA of 17 mosquitoes and 46 flies. There was no difference in the number of species recovered per individual insect between mosquitoes and flies, but the number of flies captured was higher, resulting in more mammal species recovered by flies. Eight species were recorded exclusively by mosquitoes and 20 by flies, suggesting that using both samplers would allow a more comprehensive screening of the biodiversity. The maximum distance recorded was 337 m for flies and 289 m for mosquitoes, but the average range distance did not differ between insect groups. Our assay proved to be efficient for mammal detection, considering the high number of species detected with a reduced sampling effort.

Loss of S-nitrosoglutathione reductase disturbs phytohormone homeostasis and regulates shoot side branching and fruit growth in tomato.

S-Nitrosoglutathione plays a central role in nitric oxide (NO) homeostasis, and S-nitrosoglutathione reductase (GSNOR) regulates the cellular levels of S-nitrosoglutathione across kingdoms. Here, we investigated the role of endogenous NO in shaping shoot architecture and controlling fruit set and growth in tomato (Solanum lycopersicum). SlGSNOR silencing promoted shoot side branching and led to reduced fruit size, negatively impacting fruit yield. Greatly intensified in slgsnor knockout plants, these phenotypical changes were virtually unaffected by SlGSNOR overexpression. Silencing or knocking out of SlGSNOR intensified protein tyrosine nitration and S-nitrosation and led to aberrant auxin production and signaling in leaf primordia and fruit-setting ovaries, besides restricting the shoot basipetal polar auxin transport stream. SlGSNOR deficiency triggered extensive transcriptional reprogramming at early fruit development, reducing pericarp cell proliferation due to restrictions on auxin, gibberellin, and cytokinin production and signaling. Abnormal chloroplast development and carbon metabolism were also detected in early-developing NO-overaccumulating fruits, possibly limiting energy supply and building blocks for fruit growth. These findings provide new insights into the mechanisms by which endogenous NO fine-tunes the delicate hormonal network controlling shoot architecture, fruit set, and post-anthesis fruit development, emphasizing the relevance of NO-auxin interaction for plant development and productivity.

Analysis of LruC lipoprotein and identification of peptides candidates for vaccine development and diagnosis of leptospirosis.

Leptospirosis is a public health concern with lethality around 15% of the total cases. The current vaccines against Leptospira infection based on bacterins have several limitations, which require urgent development of new ones. In this context, groundbreaking approaches such as peptide-vaccines could be used to come around with promising results. Our goal was to identify conserved and immunogenic epitopes from the lipoprotein LruC that could interact with Major Histocompatibility Complex (MHC) I and II. LruC is a conserved lipoprotein expressed during leptospirosis that is considered among vaccine candidates and can be used as source for development of peptide-based vaccines. We searched for peptides that would be recognized by antibodies from either serum of hamsters previously immunized with low-LPS bacterin vaccines or from serum of patients diagnosed with leptospirosis. Immuno properties of seven peptides from LruC protein were evaluated in silico and by Dot Blot assay, and validate by ELISA. Preliminary results pointed one promising peptide that was recognized by the sera. In conclusion, the immunoinformatic approach helps the search and screening of peptides, while the Dot Blot assay, a simple and effective tool, helps to test and validate them. Thus, these prospective techniques together were validated to identify and validate potential peptides for further investigation as peptide-based vaccines or diagnostic methods.

Coevolutionary Implications of Obligate Commensalism in Sea Turtles: the Case of the Genus Hyachelia Barnard, 1967 (Crustacea, Amphipoda).

Obligate commensalism in the marine environment and its evolutionary role are still poorly understood. Although sea turtles may serve as ideal substrates for epibionts, within amphipods, only the genus Hyachelia evolved in obligate commensalism with turtles. Here, we report a new host record for Hyachelia lowryi on the hawksbill turtle and describe a larger distribution of the genus in the Atlantic Ocean on green and loggerhead turtles. Hyachelia spp. were sampled from nesting sites of Caretta caretta and feeding grounds of Eretmochelys imbricata and Chelonia mydas along the Brazilian coast. Insights regarding the coevolution of this remarkable genus with its hosts based on molecular analyses are inferred based on mitochondrial (COI) and nuclear (18SrRNA) genes using new and previously available sequences from the infraorder Talitrida. Divergence times for Hyachelia are around the Cretaceous (~127.66 Mya), corresponding to an ancient origin and in agreement with modern green turtle (Chelonioidea) radiation. Later, diversification of Hyachelia species is dated at about 26 Mya, suggesting a coevolutionary association between amphipods and Carettini/Chelonini sea turtles.

Incidência de câncer de mama em trabalhadoras agrícolas do Paraná / Incidence of breast cancer in female agricultural workers in Paraná / Incidencia de cáncer de mama en trabajadoras agrícolas de Paraná

É crescente, nas últimas duas décadas, o número de estudos brasileiros sobre a incidência do câncer de mama, contudo, ainda há carência de trabalhos que avaliem este indicador em populações agrícolas. Objetivou-se analisar a incidência de câncer de mama feminino em trabalhadoras agrícolas residentes no estado do Paraná, no período de 2003 a 2018. Foi realizado um estudo ecológico, exploratório, transversal, constituído pelos casos novos de mulheres diagnosticadas com câncer de mama notificados no Registro Hospitalar de Câncer, entre 2003 e 2018. Calculou-se a taxa de incidência dos novos casos de câncer de mama, usando como referência o número de trabalhadoras agrícolas registradas na Relação Anual de Informações Sociais (RAIS). A regressão linear simples foi utilizada para avaliar as variações anuais da taxa, com intervalo de confiança de 95% (IC95%). E ainda, foram estimadas as Razão de Chances ou Odds Ratio (OR) (IC95%) de ocorrência do agravo para esse grupo ocupacional. A taxa de incidência variou de 136,61 casos por 100 mil trabalhadoras agrícolas em 2003 a 1.225,49/100 mil em 2018. Houve acréscimo significativo de 0,014 casos/100 mil a cada ano (p<0,001) ao longo dos 16 anos da série temporal. As trabalhadoras agrícolas tiveram, em todo o período, maiores chances de desenvolver câncer de mama, quando comparadas com trabalhadoras de outros setores (OR 14,85, IC95% 12,70 - 17,36 em 2018). Conclui-se que a incidência do câncer de mama em trabalhadoras agrícolas é significativa no Paraná e que, ser estar empregada neste setor, aumentou significativamente as chances de desenvolver câncer de mama. A partir desses dados, espera-se auxiliar na elaboração de políticas, orientando prioridades e ações de redução da incidência e mortalidade deste agravo, contribuindo com o alcance da meta 3 "saúde e bem estar' dos Objetivos do Desenvolvimento Sustentável (ODS).

In the last two decades, the number of Brazilian studies on the incidence of breast cancer has been increasing; however, there is still a lack of studies that evaluate this indicator in agricultural populations. We aimed to analyze the incidence of female breast cancer in agricultural workers residing in the state of Paraná, in the period from 2003 to 2018. An ecological, exploratory, cross-sectional study was conducted, consisting of the new cases of women diagnosed with breast cancer notified in the Hospital Cancer Registry, between 2003 and 2018. The incidence rate of new cases of breast cancer was calculated, using as reference the number of female agricultural workers registered in the Annual Social Information Report (RAIS). Simple linear regression was used to evaluate the annual variations of the rate, with a 95% confidence interval (95% CI). We also estimated the Odds Ratio (OR) (95%CI) of occurrence of the grievance for this occupational group. The incidence rate ranged from 136.61 cases per 100,000 female agricultural workers in 2003 to 1,225.49/100,000 in 2018. There was a significant increase of 0.014 cases/100 thousand each year (p<0.001) over the 16 years of the time series. Female agricultural workers had higher odds of developing breast cancer over the entire period compared to female workers in other sectors (OR 14.85, 95% CI 12.70 - 17.36 in 2018). It is concluded that the incidence of breast cancer in female agricultural workers is significant in Paraná and that being a worker in this sector, significantly increases the chances of developing breast cancer. From these data, it is expected to assist in policymaking, guiding priorities and actions to reduce the incidence and mortality of this grievance, contributing to the achievement of goal 3 'health and well-being' of the Sustainable Development Goals (SDGs).

En las últimas dos décadas, el número de estudios brasileños sobre la incidencia de cáncer de mama ha ido en aumento, sin embargo, todavía hay una falta de estudios que evalúen este indicador en poblaciones agrícolas. Tuvimos como objetivo analizar la incidencia de cáncer de mama femenino en trabajadoras agrícolas residentes en el estado de Paraná, en el período de 2003 a 2018. Se realizó un estudio ecológico, exploratorio, transversal, constituido por los casos nuevos de mujeres con diagnóstico de cáncer de mama notificados en el Registro Hospitalario de Cáncer, entre 2003 y 2018. Se calculó la tasa de incidencia de nuevos casos de cáncer de mama, tomando como referencia el número de trabajadoras agrarias registradas en el Informe Anual de Información Social (RAIS). Se utilizó regresión lineal simple para evaluar las variaciones anuales de la tasa, con un intervalo de confianza del 95% (IC 95%). También se estimó la Odds Ratio (OR) (IC 95%) de ocurrencia del agravio para este grupo ocupacional. La tasa de incidencia osciló entre 136,61 casos por 100.000 trabajadoras agrarias en 2003 y 1.225,49/100.000 en 2018. Hubo un aumento significativo de 0,014 casos/100 mil cada año (p<0,001) a lo largo de los 16 años de la serie temporal. Las trabajadoras agrícolas tuvieron mayores probabilidades de desarrollar cáncer de mama durante todo el período en comparación con las trabajadoras de otros sectores (OR 14,85; IC 95% 12,70 - 17,36 en 2018). Se concluye que la incidencia de cáncer de mama en trabajadoras agrícolas es significativa en Paraná y que ser trabajadora de este sector, aumenta significativamente las probabilidades de desarrollar cáncer de mama. A partir de estos datos, se espera ayudar en la formulación de políticas, orientando prioridades y acciones para reducir la incidencia y mortalidad de este agravio, contribuyendo a la consecución del objetivo 3 'salud y bienestar' de los Objetivos de Desarrollo Sostenible (ODS).

Molecular evolution and signatures of selective pressures on Bos, focusing on the Nelore breed (Bos indicus).

Evolutionary history leads to genome changes over time, especially for species that have experienced intense selective pressures over a short period. Here, we investigated the genomic evolution of Bos species by searching for potential selection signatures, focusing on Nelore, an economically relevant cattle breed in Brazil. We assessed the genomic processes determining the molecular evolution across Nelore and thirteen other related taxa by evaluating (i) amino acid sequence conservation, (ii) the dN/dS ratio, and (iii) gene families' turnover rate (λ). Low conserved regions potentially associated with fatty acid metabolism seem to reflect differences in meat fat content in taxa with different evolutionary histories. All Bos species presented genes under positive selection, especially B. indicus and Nelore, which include transport protein cobalamin, glycolipid metabolism, and hormone signaling. These findings could be explained by constant selective pressures to obtain higher immune resistance and efficient metabolism. The gene contraction rate across the Nelore + B. indicus branch was almost nine times higher than that in other lineages (λ = 0.01043 vs. 0.00121), indicating gene losses during the domestication process. Amino acid biosynthesis, reproductive and innate immune system-related pathways were associated with genes recognized within the most frequent rapidly evolving gene families and in genes under positive selection, supporting the substantial relevance of such traits from a domestication perspective. Our data provide new insights into how the genome may respond to intense artificial selection in distinct taxa, and reinforces the presence of selective pressures on traits potentially relevant for future animal breeding investments.

Antibodies as Snakebite Antivenoms: Past and Future.

Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab')2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.

Chagas disease (CD) affects at least 6 million people in 21 South American countries besides several thousand in other nations all over the world. It is estimated that at least 14,000 people die every year of CD. Since vaccines are not available, chemotherapy remains of pivotal relevance. About 30% of the treated patients cannot complete the therapy because of severe adverse reactions. Thus, the search for novel drugs is required. Here we tested the benznidazole (BZ) combination with the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) upon Trypanosoma cruzi in vitro and in vivo. DETC-BZ combination was synergistic diminishing epimastigote proliferation and enhancing selective indexes up to over 10-fold. DETC was effective upon amastigotes of the BZ- partially resistant Y and the BZ-resistant Colombiana strains. The combination reduced proliferation even using low concentrations (e.g., 2.5 µM). Scanning electron microscopy revealed membrane discontinuities and cell body volume reduction. Transmission electron microscopy revealed remarkable enlargement of endoplasmic reticulum cisternae besides, dilated mitochondria with decreased electron density and disorganized kinetoplast DNA. At advanced stages, the cytoplasm vacuolation apparently impaired compartmentation. The fluorescent probe H2-DCFDA indicates the increased production of reactive oxygen species associated with enhanced lipid peroxidation in parasites incubated with DETC. The biochemical measurement indicates the downmodulation of thiol expression. DETC inhibited superoxide dismutase activity on parasites was more pronounced than in infected mice. In order to approach the DETC effects on intracellular infection, peritoneal macrophages were infected with Colombiana trypomastigotes. DETC addition diminished parasite numbers and the DETC-BZ combination was effective, despite the low concentrations used. In the murine infection, the combination significantly enhanced animal survival, decreasing parasitemia over BZ. Histopathology revealed that low doses of BZ-treated animals presented myocardial amastigote, not observed in combination-treated animals. The picrosirius collagen staining showed reduced myocardial fibrosis. Aminotransferase de aspartate, Aminotransferase de alanine, Creatine kinase, and urea plasma levels demonstrated that the combination was non-toxic. As DSF and DETC can reduce the toxicity of other drugs and resistance phenotypes, such a combination may be safe and effective.

Genetic Diversity and Population Structure of Jubaea chilensis, an Endemic and Monotype Gender from Chile, Based on SNP Markers.

Jubaea chilensis (Molina) Baill., also named Chilean palm, is an endemic species found in the coastal area of Mediterranean sclerophyllous forest in Chile. It has a highly restricted and fragmented distribution along the coast, being under intense exploitation and anthropogenic impact. Based on 1038 SNP markers, we evaluated the genetic diversity and population structure among six J. chilensis natural groups encompassing 96% of the species distribution. We observed low levels of genetic diversity, a deficit of heterozygotes (mean HE = 0.024; HO = 0.014), and high levels of inbreeding (mean FIS = 0.424). The fixation index (FST) and Nei's genetic distance pairwise comparisons indicated low to moderate structuring among populations. There was no evidence of isolation by distance (r = -0.214, p = 0.799). In the cluster analysis, we observed a closer relationship among Culimo, Cocalán, and Candelaria populations. Migration rates among populations were low, except for some populations with moderate values. The K value that best represented the spatial distribution of genetic diversity was ∆K = 3. Habitat fragmentation, deterioration of the sclerophyllous forest, lack of long-distance dispersers, and a natural regeneration deficit may have driven inbreeding and low levels of genetic diversity in the palm groves of J. chilensis. Although extant populations are not at imminent risk of extinction, the rate of inbreeding could increase and migration could decrease if the effects of climate change and human impact become more acute.

Equine Anti-SARS-CoV-2 Serum (ECIG) Binds to Mutated RBDs and N Proteins of Variants of Concern and Inhibits the Binding of RBDs to ACE-2 Receptor.

The COVID-19 pandemic caused by the severe acute syndrome virus 2 (SARS-CoV-2) has been around since November 2019. As of early June 2022, more than 527 million cases were diagnosed, with more than 6.0 million deaths due to this disease. Coronaviruses accumulate mutations and generate greater diversity through recombination when variants with different mutations infect the same host. Consequently, this virus is predisposed to constant and diverse mutations. The SARS-CoV-2 variants of concern/interest (VOCs/VOIs) such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28/P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) have quickly spread across the world. These VOCs and VOIs have accumulated mutations within the spike protein receptor-binding domain (RBD) which interacts with the angiotensin-2 converting enzyme (ACE-2) receptor, increasing cell entry and infection. The RBD region is the main target for neutralizing antibodies; however, other notable mutations have been reported to enhance COVID-19 infectivity and lethality. Considering the urgent need for alternative therapies against this virus, an anti-SARS-CoV-2 equine immunoglobulin F(ab')2, called ECIG, was developed by the Butantan Institute using the whole gamma-irradiated SARS-CoV-2 virus. Surface plasmon resonance experiments revealed that ECIG binds to wild-type and mutated RBD, S1+S2 domains, and nucleocapsid proteins of known VOCs, including Alpha, Gamma, Beta, Delta, Delta Plus, and Omicron. Additionally, it was observed that ECIG attenuates the binding of RBD (wild-type, Beta, and Omicron) to human ACE-2, suggesting that it could prevent viral entry into the host cell. Furthermore, the ability to concomitantly bind to the wild-type and mutated nucleocapsid protein likely enhances its neutralizing activity of SARS-CoV-2. We postulate that ECIG benefits COVID-19 patients by reducing the infectivity of the original virus and existing variants and may be effective against future ones. Impacting the course of the disease, mainly in the more vulnerable, reduces infection time and limits the appearance of new variants by new recombination.

Pathophysiology of COVID-19: Critical Role of Hemostasis.

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.

Evolution, Expression Patterns, and Distribution of Novel Ribbon Worm Predatory and Defensive Toxins.

Ribbon worms are active predators that use an eversible proboscis to inject venom into their prey and defend themselves with toxic epidermal secretions. Previous work on nemertean venom has largely focused on just a few species and has not investigated the different predatory and defensive secretions in detail. Consequently, our understanding of the composition and evolution of ribbon worm venoms is still very limited. Here, we present a comparative study of nemertean venom combining RNA-seq differential gene expression analyses of venom-producing tissues, tandem mass spectrometry-based proteomics of toxic secretions, and mass spectrometry imaging of proboscis sections, to shed light onto the composition and evolution of predatory and defensive toxic secretions in Antarctonemertes valida. Our analyses reveal a wide diversity of putative defensive and predatory toxins with tissue-specific gene expression patterns and restricted distributions to the mucus and proboscis proteomes respectively, suggesting that ribbon worms produce distinct toxin cocktails for predation and defense. Our results also highlight the presence of numerous lineage-specific toxins, indicating that venom evolution is highly divergent across nemerteans, producing toxin cocktails that might be finely tuned to subdue different prey. Our data also suggest that the hoplonemertean proboscis is a highly specialized predatory organ that seems to be involved in a variety of biological functions besides predation, including secretion and sensory perception. Overall, our results advance our knowledge into the diversity and evolution of nemertean venoms and highlight the importance of combining different types of data to characterize toxin composition in understudied venomous organisms.

The state of Medusozoa genomics: current evidence and future challenges.

Medusozoa is a widely distributed ancient lineage that harbors one-third of Cnidaria diversity divided into 4 classes. This clade is characterized by the succession of stages and modes of reproduction during metagenic lifecycles, and includes some of the most plastic body plans and life cycles among animals. The characterization of traditional genomic features, such as chromosome numbers and genome sizes, was rather overlooked in Medusozoa and many evolutionary questions still remain unanswered. Modern genomic DNA sequencing in this group started in 2010 with the publication of the Hydra vulgaris genome and has experienced an exponential increase in the past 3 years. Therefore, an update of the state of Medusozoa genomics is warranted. We reviewed different sources of evidence, including cytogenetic records and high-throughput sequencing projects. We focused on 4 main topics that would be relevant for the broad Cnidaria research community: (i) taxonomic coverage of genomic information; (ii) continuity, quality, and completeness of high-throughput sequencing datasets; (iii) overview of the Medusozoa specific research questions approached with genomics; and (iv) the accessibility of data and metadata. We highlight a lack of standardization in genomic projects and their reports, and reinforce a series of recommendations to enhance future collaborative research.

Cuidados paliativos: desafios para o ensino em saúde / Palliative care: challenges for health education / Cuidados paliativos: los desafíos para la enseñanza en salud

Resumo Esta revisão de literatura objetivou analisar a produção acerca dos cuidados paliativos e da formação de profissionais da saúde durante a graduação. Foi realizada revisão integrativa de literatura na base Periódicos Capes, com os descritores "cuidados paliativos" e "ensino", apenas em português, dos últimos cinco anos. Dos 61 artigos encontrados, após filtros e leitura de título e resumo, foram selecionados dez. Constatou-se que as grades curriculares da maioria dos cursos de saúde não incluem o ensino dos cuidados paliativos, ocasionando despreparo teórico, prático e psicológico. Evidenciou-se o papel fundamental que a filosofia e a bioética têm na formação dos profissionais de saúde, como indutoras de condutas profissionais mais éticas, adequadas e humanas. A dinâmica teoria-prática foi a mais sugerida como forma de inserir adequadamente os cuidados paliativos no processo de formação dos cursos de saúde.

Abstract This integrative literature review analyzed the scientific production on palliative care and the education of health undergraduates. Data was collected by searching the Periódicos Capes database, using the descriptors " cuidados paliativos " (palliative care) and " ensino " (education), only in Portuguese, filtering for the last five years. After reading of titles and abstracts, ten articles were selected from the 61 found. Results show that the curricula of most health programs do not include palliative care education, resulting in theoretical, practical, and psychological unpreparedness. The analysis highlighted the key role played by philosophy and bioethics in the education of health professionals, inducing more ethical, appropriate, and humane professional conduct. The theory-practice dynamics was the most suggested as a means of properly introducing palliative care in the training process of health programs.

Resumen Esta revisión bibliográfica tenía como objetivo analizar la producción sobre los cuidados paliativos y la formación de los profesionales de la salud durante el pregrado. Se realizó una revisión bibliográfica integradora en la base Periódicos Capes, con los descriptores "cuidados paliativos" y "enseñanza", solo en portugués, de los últimos cinco años. De los 61 artículos encontrados, después de filtrar y leer el título y el resumen, se seleccionaron diez. Se comprobó que los planes de estudio de la mayoría de los cursos de salud no incluyen la enseñanza de los cuidados paliativos, ocasionando falta de preparación teórica, práctica y psicológica. Se ha demostrado el papel fundamental que la filosofía y la bioética tienen en la formación de los profesionales de la salud, como inductoras de conductas profesionales más éticas, adecuadas y humanas. La dinámica teoría-práctica fue la más sugerida como forma de insertar adecuadamente los cuidados paliativos en el proceso de formación de los cursos de salud.

Câncer de próstata em trabalhadores rurais expostos a agrotóxicos: revisão de escopo / Prostate cancer in rural workers exposed to agrochemicals: scope review

Desde o início dos anos 2000 é crescente o número de estudos que avaliam a exposição a agrotóxicos e suas consequências para a saúde do trabalhador. Contudo, não há sistematização da produção relacionada ao câncer de próstata em trabalhadores rurais. Assim, objetivou-se mapear a literatura que trata da associação entre a exposição aos agrotóxicos e a ocorrência de câncer de próstata em trabalhadores rurais. Foi realizada uma revisão de escopo nas bases de dados Web of Science (WoS), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINHAL) e Biblioteca Virtual em Saúde (BVS), empregando os descritores "Agrochemicals", "Farmers" e "Prostatic Neoplasms". Dezenove artigos fizeram parte desta revisão. Em dezessete, verificou-se associações entre a ocorrência de câncer de próstata em trabalhadores rurais e a exposição a agrotóxicos. Os fatores de risco relacionados foram: histórico familiar, tabagismo, raça/cor, idade avançada, alterações genéticas, toneladas de soja produzidas e o uso de agrotóxicos específicos. A literatura aponta a existência de consistência e plausibilidade biológica para a ocorrência de câncer de próstata em indivíduos expostos a agrotóxicos que exercem atividades agrícolas.

Since the early 2000s there has been an increasing number of studies evaluating pesticide exposure and its consequences for worker health. However, they are not systematized in relation to prostate cancer in rural workers. We aimed to map the literature dealing with the association between exposure to pesticides and the occurrence of prostate cancer in rural workers. A scoping review was conducted in the Web of Science (WoS), Scopus, Cumulative Index to Nursing and Allied Health Abstract Literature (CINHAL) and Virtual Health Library (VHL) databases. The descriptors "Agrochemicals", "Farmers" and "Prostatic Neoplasms" were employed. Nineteen articles were part of this review. In seventeen articles, associations were found between the occurrence of prostate cancer in rural workers and exposure to agrochemicals. The related risk factors were: family history, smoking, race/color, advanced age, genetic alterations, tons of soybeans produced, and the use of specific pesticides. The literature points to the existence of consistency and biological plausibility for the occurrence of prostate cancer in individuals exposed to pesticides who perform agricultural activities.

Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses.

A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.

Systems Biology Applied to the Study of Papaya Fruit Ripening: The Influence of Ethylene on Pulp Softening.

Papaya is a fleshy fruit that undergoes fast ethylene-induced modifications. The fruit becomes edible, but the fast pulp softening is the main factor that limits the post-harvest period. Papaya fast pulp softening occurs due to cell wall disassembling coordinated by ethylene triggering that massively expresses pectinases. In this work, RNA-seq analysis of ethylene-treated and non-treated papayas enabled a wide transcriptome overview that indicated the role of ethylene during ripening at the gene expression level. Several families of transcription factors (AP2/ERF, NAC, and MADS-box) were differentially expressed. ACO, ACS, and SAM-Mtase genes were upregulated, indicating a high rate of ethylene biosynthesis after ethylene treatment. The correlation among gene expression and physiological data demonstrated ethylene treatment can indeed simulate ripening, and regulation of changes in fruit color, aroma, and flavor could be attributed to the coordinated expression of several related genes. Especially about pulp firmness, the identification of 157 expressed genes related to cell wall metabolism demonstrated that pulp softening is accomplished by a coordinated action of several different cell wall-related enzymes. The mechanism is different from other commercially important fruits, such as strawberry, tomato, kiwifruit, and apple. The observed behavior of this new transcriptomic data confirms ethylene triggering is the main event that elicits fast pulp softening in papayas.