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Este estudo objetiva apreender as relações de trabalho e a realidade social do trabalhador no processo de exploração análoga à de escravo como uma violação dos direitos humanos, visando sistematizar analiticamente o debate teórico-prático e impulsionar medidas de enfrentamento que permeiam essa expressão da questão social. Trata-se de pesquisa qualitativa de caráter exploratório, cujos dados decorrem de fontes bibliográfica e documental, epistemologicamente centrada no método dialético crítico. Os resultados apontam que o Trabalho Análogo ao de Escravo (TAE), além de configurar uma violação dos direitos humanos, torna-se elemento constitutivo da precariedade estrutural, pois gera a precarização salarial que se manifesta nas condições de trabalho, nos modos e condições de vida do trabalhador. Em relação às práticas de TAE, a maior incidência em 2023 ocorreu nas regiões Sudeste e Centro-Oeste, com a realização do labor na esfera de setores produtivos como agricultura, pecuária, construção civil, carvoaria e trabalho doméstico, abrangendo área rural e urbana.

RESUMO Objetivo investigar os aspectos cognitivos relacionados à orientação temporoespacial, atenção concentrada auditiva, percepção visual, memória, habilidades aritméticas, linguagem, praxias e funções executivas em indivíduos jovens adultos com transtorno do zumbido. Métodos estudo analítico de coorte, quantitativo e transversal. Participaram 39 indivíduos, distribuídos em dois grupos: grupo com transtorno do zumbido (G1) e grupo sem o sintoma (G2). Todos foram submetidos à anamnese, inspeção visual do meato acústico externo, audiometria tonal liminar, logoaudiometria, medidas de imitância acústica, avaliação comportamental do processamento auditivo central, Escala de Autopercepção de Habilidades do Processamento Auditivo Central e Instrumento de Avaliação Neuropsicológica Breve . A análise de comparação foi realizada entre os grupos pelo escore total, habilidades cognitivas e, posteriormente, por tarefas, utilizando o Teste U de Mann-Whitney. Resultados houve diferença estatisticamente significativa entre os grupos quando realizada a análise pelo escore total, observando-se pior desempenho nos aspectos cognitivos dos indivíduos com zumbido. Ainda, houve diferença significativa entre os grupos na habilidade de praxia, na tarefa de evocação imediata e na construtiva, sendo pior nos participantes com zumbido. Conclusão os indivíduos com zumbido crônico subjetivo apresentaram desempenho cognitivo inferior aos participantes sem a percepção do sintoma.

O objetivo deste artigo é apresentar memórias da formação do Prof. Edenel, trajetória profissional e o ensino de matemática no Curso Normal do Instituto Estadual de Educação Olavo Bilac (IEEOB) no período de 1987 a 2008. A demarcação temporal foi estabelecida em função da constatação que o professor foi quem mais tempo ministrou aulas de Matemática no Curso. A metodologia da história oral foi suporte teórico-metodológico para a realização da entrevista e diálogo com as memórias. Como resultados evidenciou-se que a trajetória escolar contribuiu para a escolha da profissão professor de Matemática. A formação acadêmica foi sólida no que tange conhecimentos matemáticos, porém escassa em saberes pedagógicos. O ensino de matemática destacou conteúdos como medidas e abordagem reflexiva e crítica. Concluiu-se que a formação e trajetória profissional do entrevistado apresenta congruência e riqueza de experiências que se refletiu na atuação docente e no modo de e como ensinar Matemática.

Abstract De novo chromosome synthesis is costly and time-consuming, limiting its use in research and biotechnology. Building synthetic chromosomes from natural components is an unexplored alternative with many potential applications. In this paper, we report CReATiNG (Cloning, Reprogramming, and Assembling Tiled Natural Genomic DNA), a method for constructing synthetic chromosomes from natural components in yeast. CReATiNG entails cloning segments of natural chromosomes and then programmably assembling them into synthetic chromosomes that can replace the native chromosomes in cells. We use CReATiNG to synthetically recombine chromosomes between strains and species, to modify chromosome structure, and to delete many linked, non-adjacent regions totaling 39% of a chromosome. The multiplex deletion experiment reveals that CReATiNG also enables recovery from flaws in synthetic chromosome design via recombination between a synthetic chromosome and its native counterpart. CReATiNG facilitates the application of chromosome synthesis to diverse biological problems.

Aim: Cholesterol is an essential component of cell membranes and serves as a precursor for several bioactive molecules, including steroid hormones and isoprenoids. Generally supplied by the bloodstream, the de novo cholesterol biosynthesis is activated in response to an increased cell requirement due to normal tissue remodeling or tumor proliferation. In estrogen receptor (ER)-positive breast cancers, cholesterol biosynthesis may promote and sustain tumor growth and concur with the failure of the treatment with aromatase inhibitors. Methods: In this study, the comparison of gene compared the expression involved in cholesterol biosynthesis was conducted in ER-positive tumors that were responsive and nonresponsive to letrozole; besides, an exploration of their association with genes implicated in estrogen production, the Hippo pathway, and cell cycle control was performed. Results: In responsive tumors, letrozole significantly decreased the expression of five genes [acetyl-coenzyme A (CoA) acetyltransferase 2 (ACAT2), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), and squalene epoxidase (SQLE)] crucial for the biosynthetic process. Conversely, in nonresponsive tumors, these genes were unaffected by letrozole but associated with several genes involved in estrogens production [cytochrome P450 family 19 subfamily A member 1 (CYP19A1), hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2), and sulfotransferase family 1A member 1 (SULT1A1)], cell cycle [control cyclin dependent kinase 4 (CDK4) and CDK6], and Hippo pathway [Yes1 associated transcriptional regulator (YAP1) and baculoviral inhibitor of apoptosis (IAP) repeat containing 5 (BIRC5)]. Conclusions: The findings corroborated the notion that the dysregulation of the mevalonate pathway may contribute to the resistance to letrozole and supported the use of statins to contrast this metabolic dysfunction.

ABSTRACT: The regional lymphatic connections of the mammary glands in canines are poorly investigated, both in healthy animals and in those with mammary neoplasms. The objective was to establish the occurrence of metastases in the medial iliac lymph nodes (MILN) in bitches with mammary neoplasm, in addition to evaluating the effectiveness of the technique of lymphatic labeling of the MILN, administering methylene blue (MB) dye intrauterinely or intradermally. Thirty-two bitches with tumors in different mammary glands were included in the study. In 13 bitches (GU group), the MILNs were stained with intrauterine MB, followed by unilateral lymphadenectomy, ovariohysterectomy (OVH) and unilateral mastectomy. Nineteen bitches (GI group) underwent OVH, followed by MILN staining with intradermal MB, lymphadenectomy, and unilateral mastectomy. In GU, 11 bitches (84.62%) exhibited MB-stained MILNs, but staining was not observed in two (15.38%). Metastasis to MILNs was observed in three bitches (9.38%) from the GI and two (6.25%) from the GU. Intrauterine and intradermal staining of MILNs in bitches with mammary tumors was efficient, but intradermal administration of MB produced better results. Given metastatic spread to MILNs in approximately 15.63% of patients, we recommend that screening for MILNs should be considered as part of the staging of animals with malignant mammary neoplasms.

IntroductionMedical research and development (R&D) is an undoubtedly relevant activity to drive innovation, improve healthcare policies and bring patients treatment opportunities for common and rare diseases. Equity and inclusion are matters of concern in research. High-income countries’ research teams are more likely to have more impactful publications, grant funding, and clinical trials than middle or low-income countries. Low budget allocations to R&D and existing gaps in regulatory frameworks are some obstacles to growth. This unvirtuous cycle results in scarce advances in common endemic diseases and the underrepresentation of specific populations in innovative therapeutics research.Materials and methodsWe conducted a policy review and qualitative research to determine the principal characteristics of basic and clinical medical research in Paraguay, as well as barriers and facilitators to improve innovative R&D strategies in this country. To this aim, we examined published articles from 2005 to 2020, the organizational structure of national research agencies, the current regulation framework, and the composition and experience of local research groups and ethical review boards (ERBs). In addition, we performed semi-structured interviews to evaluate perceptions and expectations from different stakeholders, including investigators, ERBs members, sponsor associates, and Regulatory Agency executive staff.ResultsIn 2018, Paraguay ranked 10th out of 12 South American countries in total number of publications and cumulative h-index score. Total Gross Domestic Product (GDP) allocation for R&D was 0.15%, ranking eighth out of 12 in the region. In 2021, the number of trials registered on ClinicalTrials.gov was 52, with only 16 ongoing recruiting studies at that time.Some of the main barriers identified included low incentives for academic careers and lack of experience in pharmaceutical research. An emergent necessity to develop a straight- forward normative framework was detected. Main facilitators included the development of two research initiative programs (PRONII and PROCIENCIA) from CONACYT (National Council of Science and Technology) which were associated with higher budget allocation and total number of publications in the 2011 to 2017 period. A total of six stakeholders participated in the semi-structured surveys. Interviewees highlighted the necessity of a centralized policy to promote R&D, which incorporates investigators and ERBs training, the development of standardized procedures, and the dissemination of research activities. Sponsor associates underlined that real-world evidence may represent a distinctive opportunity to enhance local research.ConclusionCoordinated efforts are needed to break the unvirtuous cycle. There is an increasing interest in enhancing health research in Paraguay, materialized in the creation of specific programs that encourage the collaborative work of healthcare providers, basic scientists, and private investors. Nonetheless, a comprehensive approach is needed also to strengthen regulatory agencies and attract external sponsorship. While modern and currently popular topics, including artificial intelligence, real-world data, and translational research may represent key opportunities to seek investment, special policies should be adopted to prioritize research on the determinants of health in the Paraguayan population.

A Paracoccidioidomicose (PCM) é uma doença causada por fungo do gênero Paracoccidioides spp., com prevalência patogênica no Brasil de duas espécies, a Paracoccidioides brasiliensis e a Paracoccidioides lutzii, encontradas, principalmente, em áreas agrícolas. A transmissão está correlacionada ao manejo de solo contaminado e a via inalatória é o meio de contaminação mais comum. Trata-se de um paciente de 58 anos, residente em Ponte Nova - MG, previamente hígido, a filha procurou atendimento médico hospitalar pois encontrou o pai caído em casa. À admissão, o paciente apresentava ataxia de tronco cerebelar, dismetria, disdiadococinesia, marcha ebriosa, perda de propriocepção, incoerente com as informações e lesão ulcerosa em lábio superior esquerdo e cavidade oral (palato e língua). Filha relata que pai é etilista e tabagista de longa data. Trabalhador rural em áreas de plantações de café, exposto a paióis e aves. Foi submetido a Tomografia Computadorizada (TC) de Crânio que evidenciou múltiplas lesões disseminadas supra e infratentoriais com edema associado. Iniciado corticoide. Realizada punção liquórica onde não evidenciou alterações significativas. A TC de Tórax evidenciou infiltrado pulmonar e vidro fosco difuso com broncogramas aéreos associados. Foi descartado a possibilidade de COVID-19 e iniciado propedêutica. A TC de Fase demonstrou fratura de mandíbula esquerda, fixada cirurgicamente e neste interim foi realizado a biopsia de mucosa oral. Evoluiu com crises convulsivas com boa resposta a fenitoína. A biópsia teve como resultado imagens sugestivas de Paracoccidioides brasilienses. Com o diagnóstico de paracoccidioidomicose sistêmica (neural, pulmonar e mucosa) em paciente imunocompetente foi iniciado deoxicolato de anfotericina B 50 mg/dia. O paciente evoluiu com piora das escórias nitrogenadas e assim modificado para anfotericina B lipossomal 6,4 ampolas/dia por 13 dias. Houve melhora da função renal e clínica. Recebeu alta, em uso de sulfametoxazol/trimetropina. Avaliado pelo infectologista em ambulatório e feito troca para Itraconazol. Paciente cursou com melhora leve das lesões orais e cutâneas e dos sintomas neurológicos, mantendo discreta ataxia, déficit cognitivo. A PCM é uma doença que deve ser pensada como diagnóstico diferencial em locais onde são prevalentes, tendo um diagnóstico precoce e terapêutica adequada evolui com desfecho favorável.

O objetivo deste estudo foi compreender como ocorre o processo de gestão de startups por meio do emprego de proxies informacionais em alternativa à ausência de mecanismos formais de controle gerencial. Para o alcance deste objetivo, adotou-se como estratégia a pesquisa qualitativa básica ou genérica. Sete entrepreneurs que apresentavam formações básicas e complementares diversas, bem como experiências profissionais variadas foram entrevistados. Em relação aos achados, observou-se que as startups realizam a adoção de proxies informacionais para serem o alicerce na construção dos discursos organizacionais. As proxies identificadas são derivadas, usualmente, de artefatos formais e que se comportam como instrumentos auxiliares aos entrepreneurs/gestores no processo de tomada de decisões e no alinhamento de suas ações com os objetivos organizacionais. Por fim, os relatos obtidos e analisados neste estudo evidenciaram que, se não todas, a maiorias das proxies identificadas contribuíram, consoante suas peculiaridades, da trajetória inicial até o momento atual do negócio.

ABSTRACT The objective of this work was to characterize the internal temperature of the carcass, pH and sarcomere length in four categories of body weight at a slaughter. The categories were: category 1, animals up to 1.5 kg, category 2, animals from 1.501 to 2.5 kg, category 3, animals from 2.501 to 3.5 kg and category 4, animals over 3.501 kg. The time intervals evaluated were 0.5, 2, 4, 6, 8, 10, 12, 14, 16, 18, 24 and 36 hours after bleeding, therefore, a factorial scheme (4 x 12) was used, in which where four categories of pre-slaughter weight and the behavior of the carcasses during the post-slaughter time were evaluated. There was no interaction effect between the weight categories and the time for the variation of the carcass internal temperature, pH and sarcomere length, but when only the time of rigor was evaluated, there were significant differences for the analyzed parameters. The internal temperature of the initial average carcass (0.5 hours) was 16.02°C, reaching 3.80°C at 36 hours post-slaughter. In addition, the lowest average pH found was at 24 hours, with a value of 5.39. Regarding the sarcomere length, the smallest mean length observed was 1.41 µm at 16 hours post-slaughter and the final mean length (36 hours) was 1.89 µm. It was concluded that the analyzed margin of the categories of body weight at slaughter did not interfere in the variation of temperature, pH and sarcomere length during the post-mortem of the Pantanal caiman.

The onset and development of breast cancer in postmenopausal women are associated with closely related individual-dependent factors, including weight gain and high levels of circulating androgens. Adipose tissue is the most peripheral site of aromatase enzyme synthesis; therefore, the excessive accumulation of visceral fat results in increased androgens aromatization and estradiol production that provides the microenvironment favorable to tumorigenesis in mammary epithelial cells expressing estrogen receptors (ERs). Moreover, to meet the increased requirement of cholesterol for cell membrane assembly and the production of steroid hormones to sustain their proliferation, ER-positive cells activate de novo cholesterol biosynthesis and subsequent steroidogenesis. Several approaches have been followed to neutralize the de novo cholesterol synthesis, including specific enzyme inhibitors, statins, and, more recently, metformin. Cumulating evidence indicated that inhibiting cholesterol biosynthesis by statins and metformin may be a promising therapeutic strategy to block breast cancer progression. Unlike antiestrogens and aromatase inhibitors (AIs) which compete for binding to ER and inhibit androgens aromatization, respectively, statins block the production of mevalonic acid by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and metformin hampers the activation of the sterol regulatory element-binding protein 2 (SREBP2) transcription factor, thus inhibiting the synthesis of several enzymes involved in cholesterol biosynthesis. Noteworthy, statins and metformin not only improve the prognosis of overweight patients with ER-positive cancer but also improve the prognosis of patients with triple-negative breast cancer, the aggressive tumor subtype that lacks, at present, specific therapy.

Cholesterol (CHOL) is a multifaceted lipid molecule. It is an essential structural component of cell membranes, where it cooperates in regulating the intracellular trafficking and signaling pathways. Additionally, it serves as a precursor for vital biomolecules, including steroid hormones, isoprenoids, vitamin D, and bile acids. Although CHOL is normally uptaken from the bloodstream, cells can synthesize it de novo in response to an increased requirement due to physiological tissue remodeling or abnormal proliferation, such as in cancer. Cumulating evidence indicated that increased CHOL biosynthesis is a common feature of breast cancer and is associated with the neoplastic transformation of normal mammary epithelial cells. After an overview of the multiple biological activities of CHOL and its derivatives, this review will address the impact of de novo CHOL production on the promotion of breast cancer with a focus on mammary stem cells. The review will also discuss the effect of de novo CHOL production on in situ and invasive carcinoma and its impact on the response to adjuvant treatment. Finally, the review will discuss the present and future therapeutic strategies to normalize CHOL biosynthesis.

Abstract Background Sugarcane hemicellulosic material is a compelling source of usually neglected xylose that could figure as feedstock to produce chemical building blocks of high economic value, such as xylitol. In this context, Saccharomyces cerevisiae strains typically used in the Brazilian bioethanol industry are a robust chassis for genetic engineering, given their robustness towards harsh operational conditions and outstanding fermentation performance. Nevertheless, there are no reports on the use of these strains for xylitol production using sugarcane hydrolysate. Results Potential single-guided RNA off-targets were analyzed in two preeminent industrial strains (PE-2 and SA-1), providing a database of 5′-NGG 20 nucleotide sequences and guidelines for the fast and cost-effective CRISPR editing of such strains. After genomic integration of a NADPH-preferring xylose reductase (XR), FMYX (SA-1 hoΔ::xyl1) and CENPKX (CEN.PK-122 hoΔ::xyl1) were tested in varying cultivation conditions for xylitol productivity to infer influence of the genetic background. Near-theoretical yields were achieved for all strains; however, the industrial consistently outperformed the laboratory strain. Batch fermentation of raw sugarcane straw hydrolysate with remaining solid particles represented a challenge for xylose metabolization, and 3.65 ± 0.16 g/L xylitol titer was achieved by FMYX. Finally, quantification of NADPH — cofactor implied in XR activity — revealed that FMYX has 33% more available cofactors than CENPKX. Conclusions Although widely used in several S. cerevisiae strains, this is the first report of CRISPR-Cas9 editing major yeast of the Brazilian bioethanol industry. Fermentative assays of xylose consumption revealed that NADPH availability is closely related to mutant strains’ performance. We also pioneer the use of sugarcane straw as a substrate for xylitol production. Finally, we demonstrate how industrial background SA-1 is a compelling chassis for the second-generation industry, given its inhibitor tolerance and better redox environment that may favor production of reduced sugars.

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Este artículo tiene como objetivo reflexionar sobre los primeros contactos que poseen las/os estudiantes con el Trabajo Social en su proceso de formación. Para ello se toman como insumo de análisis los programas de las materias introductorias de cuatro países latinoamericanos (Argentina, Brasil, Paraguay y Uruguay). El trabajo muestra que a pesar de las diferencias de cada país, dicha formación posee énfasis en posiciones que se enmarcan en la corriente cientificista y crítica.

The study of butterfly coloration has helped to identify the ecological pressures involved in the evolution of animal coloration. However, almost all studies that addressed this issue have focused on species that inhabit more temperate environments, leaving the species and ecological factors of tropical regions mostly understudied. Here, our purpose was to evaluate whether butterfly assemblages from two distinct Neotropical biomes (i.e., tropical rainforest and xeric white forest) differ regarding their melanism and/or color saturation. Our hypotheses were that (1) tropical rainforest butterflies should be more melanic and color saturated, and that (2) butterflies from more open/arid tropical environments should be more melanic on their dorsal wing surfaces than on their ventral wings. Therefore, we quantified melanism and color saturation from dorsal and ventral surfaces of 121 different butterfly species. Comparisons show that rainforest butterflies, when contrasted to white forest butterflies, have more melanic dorsal wing surfaces, which might be seen as a form of protection against parasites. Our data also show that rainforest butterflies, but not white forest species, have darker dorsal wing surfaces, when compared to their own ventral surfaces, a trend that was also found for species inhabiting both biomes, which might be associated to thermoregulatory advantages. At last, our results also point that butterflies' dorsal wing sides present a higher variance between species (regardless of Biome), when compared to their own ventral wing side, an indication that some ecological factor (e.g., predation avoidance) might be exerting a strong homogenizing force on ventral wing coloration.

The production of fish flour is an alternative for better use of the raw material, although it is rarely used in instant food. Thus, the aimed of this study was to evaluate Oreochromis niloticus (Nile tilapia) and Cynoscion virescens (croaker) fillets and the elaboration of flour with filleting by-products for inclusion in food products. Carcasses and heads of the two fish species were cooked, pressed, ground, subjected to drying and re-grinding to obtain standardized flours. These carcass flours were seasoned (sweet and salted). This study was organized into two experimental tests: Test 1: Yield, physicochemical and microbiological analyzes of fillets and flours made from carcass and head of Nile tilapia and croaker; Test 2: Seasoned flours made from Nile tilapia carcasses. There was a difference in fillets yield, where the croaker demonstrated 46.56% and the Nile tilapia 32.60%. Nile tilapia fillets had higher protein content (17.08%) and lower lipid content (0.89%) compared to croaker fillets (14.21 and 4.45%). Nile tilapia backbone flour had the highest protein content (55.41%) and the croaker the highest ash (45.55%) and the lowest Nile tilapia (28.38%). The head flours had lower protein contents (39.86%). Flours produced with croaker backbone had higher levels of calcium and phosphorus (9.34 and 9.27%). However, Nile tilapia backbone flour showed higher contents of essential amino acids. These flours demonstrated a fine granulometry (0.23 to 0.56 mm). Seasoned flours demonstrated interaction between fish species and flavors for moisture, ash, carbohydrates, calcium and phosphorus. The highest protein content (29.70%) was for Nile tilapia flour sweet flours (31.28%) had higher protein content, while salted lipids (8.06%). Nile tilapia has a lower fillet yield, although with a high protein content and low lipid content. Comparing the flours made from filleting by-products, the backbone flour has better nutritional quality, with Nile tilapia being superior to that of croaker, especially in terms of protein and amino acids.

Abstract Background Saccharomyces cerevisiae is largely applied in many biotechnological processes, from traditional food and beverage industries to modern biofuel and biochemicals factories. During the fermentation process, yeast cells are usually challenged in different harsh conditions, which often impact productivity. Regarding bioethanol production, cell exposure to acidic environments is related to productivity loss on both first- and second-generation ethanol. In this scenario, indigenous strains traditionally used in fermentation stand out as a source of complex genetic architecture, mainly due to their highly robust background—including low pH tolerance. Results In this work, we pioneer the use of QTL mapping to uncover the genetic basis that confers to the industrial strain Pedra-2 (PE-2) acidic tolerance during growth at low pH. First, we developed a fluorescence-based high-throughput approach to collect a large number of haploid cells using flow cytometry. Then, we were able to apply a bulk segregant analysis to solve the genetic basis of low pH resistance in PE-2, which uncovered a region in chromosome X as the major QTL associated with the evaluated phenotype. A reciprocal hemizygosity analysis revealed the allele GAS1, encoding a β-1,3-glucanosyltransferase, as the casual variant in this region. The GAS1 sequence alignment of distinct S. cerevisiae strains pointed out a non-synonymous mutation (A631G) prevalence in wild-type isolates, which is absent in laboratory strains. We further showcase that GAS1 allele swap between PE-2 and a low pH-susceptible strain can improve cell viability on the latter of up to 12% after a sulfuric acid wash process. Conclusion This work revealed GAS1 as one of the main causative genes associated with tolerance to growth at low pH in PE-2. We also showcase how GAS1 PE-2 can improve acid resistance of a susceptible strain, suggesting that these findings can be a powerful foundation for the development of more robust and acid-tolerant strains. Our results collectively show the importance of tailored industrial isolated strains in discovering the genetic architecture of relevant traits and its implications over productivity.