Answering the Cell Stress Call: Satellite Non-Coding Transcription as a Response Mechanism.

Organisms are often subjected to conditions that promote cellular stress. Cell responses to stress include the activation of pathways to defend against and recover from the stress, or the initiation of programmed cell death to eliminate the damaged cells. One of the processes that can be triggered under stress is the transcription and variation in the number of copies of satellite DNA sequences (satDNA), which are involved in response mechanisms. Satellite DNAs are highly repetitive tandem sequences, mainly located in the centromeric and pericentromeric regions of eukaryotic chromosomes, where they form the constitutive heterochromatin. Satellite non-coding RNAs (satncRNAs) are important regulators of cell processes, and their deregulation has been associated with disease. Also, these transcripts have been associated with stress-response mechanisms in varied eukaryotic species. This review intends to explore the role of satncRNAs when cells are subjected to adverse conditions. Studying satDNA transcription under various stress conditions and deepening our understanding of where and how these sequences are involved could be a key factor in uncovering important facts about the functions of these sequences.

Development of a QCM-based biosensor for the detection of non-small cell lung cancer biomarkers in liquid biopsies.

Lung cancer is the main malignant cancer reported worldwide, with one of the lowest survival rates. Deletions in the Epidermal Growth Factor Receptor (EGFR) gene are often associated with non-small cell lung cancer (NSCLC), a common subtype of lung cancer. The detection of such mutations provides key information for the diagnosis and treatment of the disease; therefore, the early screening of such biomarkers is of vital importance. The need for fast, reliable, and early detection means applied to NSCLC has led to the development of highly sensitive devices that can detect cancer-associated mutations. Such devices, known as biosensors, are a promising alternative to more conventional detection methods and can potentially alter the way cancer is diagnosed and treated. In this study, we report the development of a DNA-based biosensor, namely a quartz crystal microbalance (QCM), applied to the detection of NSCLC, from liquid biopsies samples. The detection, as is the case of most DNA biosensors, is based on the hybridization between the NSCLC-specific probe and the sample DNA (containing specific mutations associated with NSCLC). The surface functionalization was performed with a blocking agent (dithiothreitol) and thiolated-ssDNA strands. The biosensor was able to detect specific DNA sequences in both synthetic and real samples. Aspects such as reutilization and regeneration of the QCM electrode were also studied.

Modeling the Dynamics of Children's Musculoskeletal Fitness.

This study models children's musculoskeletal fitness (MSF) developmental trajectories and identifies individual differences related to effects of time-invariant, as well as time-varying covariates. A total of 348 Portuguese children (177 girls) from six age cohorts were followed for three years. MSF tests (handgrip strength, standing long jump and shuttle run), age, body mass index (BMI), socioeconomic status (SES), gross motor coordination (GMC) and physical activity (PA) were assessed. Data were analyzed using multilevel models. Between 5 and 11 years of age, boys outperformed girls in all three MSF tests (p < 0.05). Birth weight was positively associated with shuttle run performance (ß = -0.18 ± 0.09, p < 0.05). BMI was positively associated with handgrip strength (ß = 0.35 ± 0.04, p < 0.001) and shuttle run performance (ß = 0.06 ± 0.01, p < 0.001), but negatively associated with standing long jump performance (ß = -0.93 ± 0.23, p < 0.001). GMC was positively associated (p < 0.001) with all three MSF tests, while PA was associated with standing long jump (ß = 0.08 ± 0.02, p < 0.05) and shuttle run (ß = -0.003 ± 0.002, p < 0.05) performance only. No school environment effects were found, and SES was not related to any MSF tests. Children's MSF development showed a curvilinear shape with increasing age, with boys outperforming girls. Weight status and physical behavior characteristics predicted MSF development, while environmental variables did not. Examining potential longitudinal predictors of MSF across multiple dimensions is important to gain a more holistic understanding of children's physical development as well as to future interventions.

Human Satellite 1A analysis provides evidence of pericentromeric transcription.

BACKGROUND: Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have historically posed a challenge for the assembly of the human reference genome where they are misrepresented due to their repetitive nature. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSat1A has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of functional knowledge. Here, we aim to characterize and provide an understanding on the biological relevance of HSat1A. RESULTS: The path followed herein trails with HSat1A isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSat1A was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSat1A transcripts and further characterize them by 3' RACE-Seq. Size-varying polyadenylated HSat1A transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation. CONCLUSION: As far as we know, this work pioneers HSat1A transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSat1A sequences and associated noncoding RNAs will most certainly prove significant in the future of HSat research.

Physical and motor profile of children between 6 and 10 years old according to levels of cardiorespiratory fitness / Perfil físico e motor de crianças entre os 6 e os 10 anos de idade em função dos níveis de aptidão cardiorrespiratória

Abstract This study aimed to compare the physical profile and motor profile of children from 6 to 10 years old, according to their level of cardiorespiratory fitness (CRF). Participated 2036 children from 6 to 10 years old from São José dos Pinhais - PR. Assessed variables were stature, corporal mass, Body mass index (BMI), physical fitness (PF), and gross motor coordination (GMC). The CRF was assessed by the total distance during the 6 minutes walking test. A battery of tests KTK evaluated the GCM. The children were classified according to their levels of CRF (low-moderate-elevated). Differences between groups were tested using ANOVA one way. Data analysis was made in the SPSS software, with a meaningfulness of 5%. Children with low levels of CRF showed higher values of adiposity. On the PF tests, children with low levels of CRF showed higher values of prehension and worse performance in the other tests. Regarding GMC, children with low levels of CRF had lower coordinative performance. Meaningful differences were found in the comparisons between different groups (low-moderate, low-elevated) with an advantage in the results in moderate levels of CRF. Obtaining average levels of CRF can bring protective benefits in other variables in children's growth process and development during infancy. Evaluating the CRF doesn't only get a momentary evaluation. Still, it can also do the monitoring of an essential variable of health, as well as indicate a predisposition about other physical-motor variables.

Resumo Comparar o perfil físico e motor de crianças dos 6 aos 10 anos, conforme os seus níveis de aptidão cardiorrespiratória (AptC). Participaram do estudo 2036 crianças de seis a 10 anos de idade de São José dos Pinhais-PR. Foram avaliados estatura, massa corporal, índice de massa corporal (IMC), aptidão física (AptF) e coordenação motora (CMG). A AptC foi avaliada pela distância total percorrida no teste de seis minutos. A CMG foi avaliada por meio da bateria de testes KTK. As crianças foram classificadas em função dos níveis de AptC (baixo-moderado-elevado). Diferenças entre grupos foram testadas utilizando da ANOVA one way. As análises dos dados foram realizadas no software SPSS, com nível de significância em 5%. Crianças com menor nível de AptC apresentam maiores valores médios adiposidade. Nos testes de AptF, crianças com níveis baixos de AptC apresentaram maiores valores de preensão e pior desempenho nos demais testes. Relativamente à CMG, crianças com baixos níveis de AptC apresentaram piores desempenho coordenativo. Diferenças significativas foram encontradas para as comparações entre os outros grupos (baixo-moderado; baixo-elevado) com vantagem nos resultados nos níveis moderados a elevados de AptC. Obter níveis moderados de AptC pode trazer benefícios protetores em diferentes variáveis do processo de crescimento e desenvolvimento de crianças durante a segunda infância. Avaliar a AptC não traz somente uma avaliação momentânea, como pode ser feito o monitoramento de uma importante variável de saúde bem como indicar uma predisposição sobre outras variáveis físico-motoras.

Development of multi-residue gas chromatography coupled with mass spectrometry methodologies for the measurement of 15 chemically different disinfection by-products (DBPs) of emerging concern in drinking water from two different Portuguese water treatment plants.

In water treatment plants (WTPs), chemical agents, such as chlorine and ozone, might react with organic matter and anthropogenic contaminants, forming a high diversity of disinfection by-products (DBPs). Due to the potential toxicological effects, the identification of unregulated DBPs (UR-DBPs) is critical to help water managers in the selection of effective water treatment processes, contributing to improving water safety plans. Given the limited validated analytical methods to detect UR-DBPs, here we developed new multi-residue gas chromatography coupled with mass spectrometry methodologies for the detection and quantification of 15 UR-DBPs, including aldehydes, haloketones (HKs), nitrosamines and alcohols, in drinking water matrices. Solid-phase extraction (SPE), for the nitrosamine group, and solid-phase micro extraction (SPME), for the remaining DBPs, were used as sample preparation methods. The developed methodologies allowed the quantification of target UR-DBPs at trace concentration levels (ng L-1), with method quantification limits (MQLs) ranging from 14.4 ng L-1 to 26.0 ng L-1 (SPE-GC-MS) and 2.3 ng L-1 and 1596 ng L-1 (SPME-GC-MS). The methods were applied to different drinking water matrices, considering distinct delivery points of EPAL - Empresa Portuguesa das Águas Livres WTPs. Overall, the aldehyde group, represented by decanal, nonanal and 2-ethylheaxanal, showed the highest occurrence, followed by HKs and nitrosamines. The results of this study suggested that the formation of these UR-DBPs should be further monitored in WTPs.

Satellite Noncoding RNAs (ncRNA) as Cancer Biomarkers? New Insights from FA-SAT ncRNA Molecular and Clinical Profiles in Feline Mammary Tumors.

Satellite noncoding RNAs (ncRNAs) are a new frontier of cancer biology research and biomarkers. While the knowledge on ncRNAs in human cancers is still limited, studies in other species can be informative to guide future translational research and development for cancer molecular targets and diagnostics. In this context, FA-SAT is the major satellite DNA of the cat genome, which is also present in humans, being transcribed in both species. In this study, we report new insights on FA-SAT (DNA and RNA) profile in feline mammary tumors, using disease-free tissues from the same animals as reference. We quantified the FA-SAT DNA and RNA levels (long and small transcripts) by real-time quantitative polymerase chain reaction (qPCR) and RT-qPCR. The comparison of the FA-SAT DNA and RNA levels with clinicopathological parameters revealed several associations, such as (1) the FA-SAT DNA levels' positive relation with lymphovascular invasion, (2) the FA-SAT long RNA negative correlation with Ki-67 index, and its positive association with Estrogen Receptor status, and (3) the FA-SAT small RNA level positive correlation with tumor size and skin ulceration. Also, FA-SAT long RNA is correlated with ERBB2 and c-MYC RNA levels. These data collectively suggest that FA-SAT ncRNA offers prospects as a potential cancer biomarker in cats. Further studies in humans are also needed to decipher the emerging role of ncRNAs in cancer biology and precision medicine fields. This work brings new information on the relation of FA-SAT ncRNAs with the oncogenic process, uncovering a new potential cancer biomarker.

Correlates of the Physical Activity Decline during Childhood.

PURPOSE: This study aimed to describe longitudinal trends in children's moderate-to-vigorous physical activity (MVPA) and to investigate associations with individual, familial, and school characteristics. METHODS: A sample of 341 Portuguese children age 5-10 yr (173 girls) from six age cohorts was followed over 3 yr using a mixed-longitudinal design. Physical activity, body mass index (BMI), gross motor coordination, and musculoskeletal fitness were assessed annually. Information on socioeconomic status and school characteristics was collected and analyzed with mixed models. RESULTS: MVPA shows a similar declining trend in both sexes, but on average, boys exceeded the World Health Organization recommendations of 60 min·d -1 . The best model showed that boys spend, on average, more time in MVPA than girls. Children with lower BMI are less prone to the decline in MVPA, whereas higher levels of musculoskeletal fitness were associated with lower declines in MVPA. Of all school characteristics, only playground dimension was related to MVPA decreasing trajectories. CONCLUSIONS: MVPA systematically declines from 5 to 10 yr of age in both boys and girls, but boys remained more active than girls across the age range. The best predictors of MVPA decline are sex, BMI, musculoskeletal fitness, and school playground dimension.

Comprehensive In Silico Analysis of Retrotransposon Insertions within the Survival Motor Neuron Genes Involved in Spinal Muscular Atrophy.

Transposable elements (TEs) are interspersed repetitive and mobile DNA sequences within the genome. Better tools for evaluating TE-derived sequences have provided insights into the contribution of TEs to human development and disease. Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that is caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene but retention of its nearly perfect orthologue SMN2. Both genes are highly enriched in TEs. To establish a link between TEs and SMA, we conducted a comprehensive, in silico analysis of TE insertions within the SMN1/2 loci of SMA, carrier and healthy genomes. We found an Alu insertion in the promoter region and one L1 element in the 3'UTR that may play an important role in alternative promoter as well as in alternative transcriptional termination. Additionally, several intronic Alu repeats may influence alternative splicing via RNA circularization and causes the presence of new alternative exons. These Alu repeats present throughout the genes are also prone to recombination events that could lead to SMN1 exons deletions and, ultimately, SMA. TE characterization of the SMA genomic region could provide for a better understanding of the implications of TEs on human disease and genomic evolution.

Assessment of Water Quality Parameters and their Seasonal Behaviour in a Portuguese Water Supply System: a 6-year Monitoring Study.

Water quality monitoring is a fundamental tool in the management of freshwater resources. The purpose of monitoring is to provide meaningful quality data for local action planning and catchment-wide decision making. The assessment of water quality is crucial to guarantee the efficient operation of the Water Treatment Plants (WTPs), promoting health conditions and contributing for a more sustainable urban water cycle. In accordance, the objective of this study was to evaluate key target chemical and microbiological water quality parameters, some of them already monitored within Portuguese/EU legal framework and others still not regulated, but with environmental and human heath relevance. A local monitoring database model, using a 6-year period (from 2014 to 2019) of water quality data, regarding water samples collected on representative sampling locations covering the freshwater abstraction sites, conventional WTPs and distribution network was assessed. This work provides new knowledge regarding occurrence and seasonal behaviour for both microbiological and chemical water quality parameters, essential to understand/manage the water supply system. Additionally, relationships between the target variables were also assessed. Particularly, strong correlations were identified between TOC and THMs formation at distribution network (r = 0.69; p ≤ 0.001); nitrates were the water quality parameter that revealed the best correlation between surface water source and treated water (r = 0.81; p ≤ 0.001), suggesting that treatment yield/performance is dependent on surface water load. The local and continuous monitoring of water systems are crucial to implement new approaches to guarantee the best quality of drinking water throughout the supply system.

Genomic Tackling of Human Satellite DNA: Breaking Barriers through Time.

(Peri)centromeric repetitive sequences and, more specifically, satellite DNA (satDNA) sequences, constitute a major human genomic component. SatDNA sequences can vary on a large number of features, including nucleotide composition, complexity, and abundance. Several satDNA families have been identified and characterized in the human genome through time, albeit at different speeds. Human satDNA families present a high degree of sub-variability, leading to the definition of various subfamilies with different organization and clustered localization. Evolution of satDNA analysis has enabled the progressive characterization of satDNA features. Despite recent advances in the sequencing of centromeric arrays, comprehensive genomic studies to assess their variability are still required to provide accurate and proportional representation of satDNA (peri)centromeric/acrocentric short arm sequences. Approaches combining multiple techniques have been successfully applied and seem to be the path to follow for generating integrated knowledge in the promising field of human satDNA biology.

Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC.

Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.

Using zebrafish embryo bioassays combined with high-resolution mass spectrometry screening to assess ecotoxicological water bodies quality status: A case study in Panama rivers.

Several studies show that many water bodies in developing countries are increasingly affected by anthropogenic pressure, such as agricultural activities, domestic and industrial wastewater. However, data is scarce in several of such countries, including Panama. Thus, in this work, the ecotoxicological status of selected rivers in Panama with distinct input sources were evaluated using the zebrafish (Danio rerio) embryo bioassays combined with a liquid chromatography-high resolution mass spectrometry screening of contaminants of emerging concern (CECs), using a library of over 3200 chemicals. A total of 68 CECs, including pharmaceuticals and metabolites, pesticides and several industrial chemicals, could be tentatively identified. Additionally, the zebrafish embryo bioassays showed a significant increase (p < 0.05) in embryo mortality/abnormalities when incubated with water samples from two rivers, Matasnillo and Curundú (47.5% and 32%, respectively). Importantly, a positive correlation between ecotoxicological endpoints and some of the detected CECs was observed. The findings demonstrate that both rivers are under strong anthropogenic pressure, and therefore, management actions are urgently needed to decrease their level of contamination. Overall, this study further supports the use of the zebrafish embryo bioassay as a fast, high throughput approach for screening the toxicity of water samples, and highlights the advantages of combining ecotoxicological assays with high-resolution mass spectrometry to an expedite assessment of the ecotoxicological status of water bodies.

Distribución espacial y variables explicativas de capturas de Thunnus albacares (Perciformes: Scombridae) y especies no objetivo por la flota internacional de cerco en el Pacífico de Costa Rica / Spatial distribution and correlates for catches of Thunnus albacares (Perciformes: Scombridae) and non-target species by the international purse-seine fleet in the Pacific of Costa Rica

Introducción: En los ambientes marinos del Pacífico de Costa Rica, la actividad pesquera por la flota cerquera internacional es importante debido a su amplio alcance y fuerte impacto. Objetivo: Evaluar la distribución espacial de la captura de atún aleta amarilla y especies no objetivo por esa flota, y posibles correlaciones con variables ambientales y pesqueras. Métodos: Aplicamos estadísticas geoespaciales y modelos de regresión múltiple en datos de la Comisión Interamericana del Atún Tropical, del 2002 al 2011. Utilizamos una grilla del tamaño de la Zona Económica Exclusiva (ZEE) con 1 124 celdas de 22 x 22 km (unidad de análisis), para un total de 11 240 celdas-año. Resultados: El atún mediano (presumiblemente inmaduro en su mayoría), delfines, mantas y rayas fueron capturados mayormente dentro del Domo Térmico (noreste de la ZEE). Las más altas capturas de atún pequeño (inmaduro en su totalidad), tiburones, picudos, dorado, peto y diversas especies pequeñas, ocurrieron en el extremo sur. El atún grande (maduro) fue capturado especialmente en el centro de la ZEE, hacia el este del Área Marina de Manejo Montes Submarinos y el Parque Nacional Marino Isla del Coco. Los atunes, dorado, delfines, mantas y rayas mostraron gran fidelidad de sitio por asociación con variables geográficas y ambientales, a la vez que el atún pequeño estuvo asociado a lances sobre objetos flotantes y el atún grande a lances sobre delfines. La heterogeneidad de las especies no objetivo probablemente escondió la mayoría de las correlaciones. Conclusiones: La pesca está afectando los niveles tróficos más altos y es necesario un diseño de zonificación ajustado para proteger mejor el domo térmico y considerar la susceptibilidad al uso de redes de cerco.

Introduction: In the Pacific marine ecosystems of Costa Rica, fishing activity by the international purse-seine fleet is important for its wide scope and large impact. Objective: To evaluate the spatial distribution of the catch of yellowfin tuna and non-target species by this fleet, and possible correlates with environmental and fishing variables. Methods: We applied geospatial statistics and multiple regression models to Inter-American Tropical Tuna Commission data, covering from 2002 to 2011. We used a grid the size of the Exclusive Economic Zone (EEZ) with 1 124 cells of 22 x 22 km (unit of analysis), for a total of 11 240 year-cells. Results: The medium tuna (presumably immature for the most part), dolphins, mantas and rays dominated catches within the Thermal Dome (Northeast of the EEZ). Small tuna (all immature), sharks, billfishes, dorado, wahoo, and various small species were caught mostly in the extreme South. Large tuna (mature) was caught specially in the zone center, towards the east of the Submarine Mounts Marine Management Area and the Isla del Coco National Marine Park. Tuna, dorado, dolphins, mantas and rays showed high site fidelity due to their association with geographic and environmental variables, at the time small tuna was associated with sets on floating objects, and big tuna was associated with sets on dolphins. The heterogeneity of non-target species probably hid most correlations. Conclusions: Fishing is affecting the highest trophic levels and an adjusted zoning design is needed to better protect the thermal dome and to take into account susceptibility to the use of purse seines.

Padrão de utilização de espaços públicos abertos e nível de atividade física em São José dos Pinhais, Paraná / Pattern of use of public open spaces and physical activity levels in São José dos Pinhais, Brazil / Patrón de uso de espacios públicos abiertos y niveles de actividade física en São José dos Pinhais, Brasil

RESUMO O objetivo deste estudo foi analisar a associação entre o padrão de utilização de espaços públicos abertos (EPA) e o nível de atividade física (AF) de intensidade moderada a vigorosa (AFMV) em São José dos Pinhais, Paraná. Sexo, faixa etária e AF foram identificados com o System for Observing Play and Recreation in Communities (SOPARC). A AFMV foi analisada considerando as categorias de sexo, local, dia da semana, horário e período. Foram realizadas 2.591 observações de pessoas e a proporção de AFMV foi de 35%. O sexo feminino apresentou associação positiva com a AFMV (OR: 1,57; IC95%: 1,32-1,86), enquanto a utilização dos EPA no final de semana (OR: 0,55; IC95%: 0,46-0,65) e no período da tarde apresentou associação inversa com o desfecho (OR: 0,57; IC95%: 0,48-0,67). Conclui-se que mulheres e aqueles que utilizam os locais durante a semana ou pela manhã apresentam maiores chances de praticarem AFMV.

ABSTRACT This study aimed to analyze the association between the pattern of use of public open spaces (POS) and moderate to vigorous physical activity (MVPA) in São José dos Pinhais, Brazil. Sex, age group, and physical activity intensity level (PA) were identified through the System for Observing Play and Recreation in Communities (SOPARC). MVPA was analyzed by sex, place, day of the week, and time. We conducted 2,591 person observations, and the proportion of MVPA was 35%. The female sex was positively associated with MVPA (OR: 1.57; 95% CI: 1.32-1.86), while the use of POS on weekend (OR: 0.55; 95% CI: 0.46 -0.65) and in the afternoon showed an inverse association with outcome (OR: 0.57; 95% CI: 0.48-0.67). In conclusion, women and the people who use POS during the week or in the morning are more likely to practice MVPA.

RESUMEN El objetivo de este estudio fue analizar la asociación entre el patrón de uso de los espacios públicos abiertos (EPA) y el nivel de actividad física moderada a vigorosa (AFMV) en São José dos Pinhais, Brasil. Sexo, edad y AF fueron evaluados con el System for Observing Play and Recreation in Communities (SOPARC). La AFMV se analizó según sexo, ubicación, día de la semana, hora y período del día. Se hicieron 2.591 observaciones de personas y la proporción de AFMV fue de 35%. El sexo femenino se asoció positivamente con AFMV (OR: 1,57; IC 95%: 1,32-1,86), mientras que el uso de EPA en lo fine de semana (OR: 0,55; IC 95%: 0,46-0,65) y por la tarde mostró una asociación inversa con el desfecho (OR: 0,57; IC 95%: 0,48-0,67). Se concluye que mujeres, las personas que utilizan los lugares durante la semana o por la mañana, tienen más probabilidades de practicar AFMV. Palabras-clave Actividad motora; Ejercicio físico; Parques recreativos; Área urbana; Planificación ambiental; Entorno construido; Técnicas de observación conductual.

Toxicological assessment of seven unregulated drinking water Disinfection By-products (DBPs) using the zebrafish embryo bioassay.

Disinfection By-products (DBPs) are formed during the chemical treatment of water for human consumption, by the reaction of raw water with chemical agents used in the different steps of the process. Disinfection is one of the most important steps, inactivating pathogens and preventing their regrowth during water distribution. However, it is also involved in DBPs formation due to the use of disinfectant agents, such as chlorine, which reacts with dissolved precursors, such as pharmaceuticals, toxins, pesticides, among others. Given their widespread occurrence, potential human health and (eco) toxicological impacts are of particular interest due to their potential carcinogenicity and various non-carcinogenic effects, such as endocrine disruption. In this study, the developmental toxicity of chemically- different unregulated DBPs was evaluated using zebrafish embryo bioassay. Embryos were exposed to different concentrations of the target DBPs and multiple endpoints, including, mortality, morphological abnormalities and locomotor behavior were assessed at specific developmental stages (24, 48, 72 and 96 hpf). The different families of DBPs tested included nitrosamines, aldehydes, alcohols and ketones. The results show that the effects were compound dependent, with EC10 values varying between 0.04 mg/L (2-ethyl-1-hexanal) to 9.2 mg/L (hexachloroacetone). Globally, several of the tested unregulated DBPs displayed higher toxicity when compared with the available data for some already regulated, such as trihalomethanes (THMs), which highlights the importance of screening the toxicity of still untested and poorly characterized DBPs.

Decoding the Role of Satellite DNA in Genome Architecture and Plasticity-An Evolutionary and Clinical Affair.

Repetitive DNA is a major organizational component of eukaryotic genomes, being intrinsically related with their architecture and evolution. Tandemly repeated satellite DNAs (satDNAs) can be found clustered in specific heterochromatin-rich chromosomal regions, building vital structures like functional centromeres and also dispersed within euchromatin. Interestingly, despite their association to critical chromosomal structures, satDNAs are widely variable among species due to their high turnover rates. This dynamic behavior has been associated with genome plasticity and chromosome rearrangements, leading to the reshaping of genomes. Here we present the current knowledge regarding satDNAs in the light of new genomic technologies, and the challenges in the study of these sequences. Furthermore, we discuss how these sequences, together with other repeats, influence genome architecture, impacting its evolution and association with disease.

FA-SAT ncRNA interacts with PKM2 protein: depletion of this complex induces a switch from cell proliferation to apoptosis.

FA-SAT is a highly conserved satellite DNA sequence transcribed in many Bilateria species. To disclose the cellular and functional profile of FA-SAT non-coding RNAs, a comprehensive experimental approach, including the transcripts location in the cell and in the cell cycle, the identification of its putative protein interactors, and silencing/ectopic expression phenotype analysis, was performed. FA-SAT non-coding RNAs play a nuclear function at the G1 phase of the cell cycle and the interactomic assay showed that the PKM2 protein is the main interactor. The disruption of the FA-SAT non-coding RNA/PKM2 protein complex, by the depletion of either FA-SAT or PKM2, results in the same phenotype-apoptosis, and the ectopic overexpression of FA-SAT did not affect the cell-cycle progression, but promotes the PKM2 nuclear accumulation. Overall, our data first describe the importance of this ribonucleoprotein complex in apoptosis and cell-cycle progression, what foresees a promising novel candidate molecular target for cancer therapy and diagnosis.

Percentile curves for Brazilian children evaluated with the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition / Curvas percentílicas para crianças brasileiras avaliadas pelo Teste de Proficiência Motora Bruininks-Oseretsky, 2ª edição

Abstract This study aimed to (1) create percentile curves and norms for the eight subtests of the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2) for 6- to 10-year-old Brazilian children and to (2) compare them to the values of the original test manual. To that, we tested a sample of 931 Brazilian children (477 girls, 454 boys) with ages between 6 to 10 with the BOT-2 assessment. The LMS method was used to generate the percentile curves and normative values, with the LMSchartmaker Pro software version 2.54. Results demonstrate that girls had significantly higher scores for the fine motor precision, fine motor integration, manual dexterity and balance subtests, while boys had significantly higher scores on upper-limb coordination, running speed and agility, and the strength subtests. The findings also indicated higher values for the Brazilian group in the subtests of bilateral coordination, running speed and agility, balance, and upper-limb coordination when compared to the North American normative sample. The percentile curves illustrate the increase in motor proficiency levels as age increases, with different trajectories for each subtest. Future studies should continue the investigation of cultural norms and appropriate assessments for the Brazilian population. Here, the creation of percentile curves and norms that are better suited for the Brazilian population can significantly help with assessment and intervention for motor development in distinct settings and with typical and atypical school-age children.

Resumo Este estudo objetivou (1) criar curvas e normas percentílicas para os oito subtestes do Teste de Proficiência Motora Bruininks-Oseretsky, 2ª edição (BOT-2) para crianças brasileiras de 6 a 10 anos e compará-las com os valores do manual de teste original. Para tanto, testamos uma amostra de 931 crianças brasileiras (477 meninas, 454 meninos) com idades entre 6 a 10 anos com a avaliação do BOT-2. O método LMS foi usado para gerar as curvas de percentil e valores normativos, utilizando o software LMSchartmaker Pro versão 2.54. Os resultados demonstram que as meninas tiveram escores significativamente mais altos nos subtestes de precisão motora fina, integração motora fina, destreza manual e equilíbrio, enquanto os meninos tiveram escores significativamente mais altos nos subtestes de coordenação de membros superiores, velocidade de corrida e agilidade e força. Os resultados também indicaram valores mais elevados para o grupo brasileiro nos subtestes de coordenação bilateral, corrida de velocidade e agilidade, equilíbrio e coordenação dos membros superiores quando comparados com a amostra normativa norte-americana. As curvas percentílicas ilustram o aumento nos níveis de proficiência motora à medida que a idade aumenta, com diferentes trajetórias para cada subteste. Estudos futuros devem continuar a investigação de normas culturais e avaliações apropriadas para a população brasileira. Neste estudo, a criação de curvas e normas percentílicas mais adequadas para a população brasileira pode ajudar significativamente na avaliação e intervenção para o desenvolvimento motor em diferentes contextos e com crianças em idade escolar típicas e atípicas.

Gene expression association study in feline mammary carcinomas.

Works on cancer-related genes expression using feline mammary carcinomas (FMCs) are scarce but crucial, not only to validate these tumours as models for human breast cancer studies but also to improve small animal practice. Here, the expression of the cancer-related genes TP53, CCND1, FUS, YBX1, PTBP1, c-MYC and PKM2 was evaluated by real-time RT-qPCR, in a population of FMCs clinically characterized and compared with the disease-free tissue of the same individual. In most of the FMCs analysed, RNA quantification revealed normal expression levels for TP53, c-MYC, YBX1 and FUS, but overexpression in the genes CCND1, PTBP1 and PKM2. The expression levels of these cancer-related genes are strongly correlated with each other, with exception of c-MYC and PKM2 genes. The integration of clinicopathological data with the transcriptional levels revealed several associations. The oral contraceptive administration showed to be positively related with the TP53, YBX1, CCND1, FUS and PTBP1 RNA levels. Positive associations were found between tumour size and YBX1 RNA, and lymph node metastasis with c-MYC RNA levels. This work allowed to verify that many of these cancer-related genes are associated but may also, indirectly, influence other genes, creating a complex molecular cancer network that in the future can provide new cancer biomarkers.