The complex channel networks of bone structure

Bone structure in mammals involves a complex network of channels (Havers and Volkmann channels) required to nourish the bone marrow cells. This work describes how three-dimensional reconstructions of such systems can be obtained and represented in terms of complex networks. Three important findings are reported: (i) the fact that the channel branching density resembles a power law implies the existence of distribution hubs; (ii) the conditional node degree density indicates a clear tendency of connection between nodes with degrees 2 and 4; and (iii) the application of the recently introduced concept of hierarchical clustering coefficient allows the identification of typical scales of channel redistribution. A series of important biological insights is drawn and discussedComment: 3 pages, 1 figure, The following article has been submitted to Applied Physics Letters. If it is published, it will be found online at http://apl.aip.org

Repeated downsweep vocalizations of the Araguaian river dolphin, Inia araguaiaensis

Funding was provided by the Swarosvki Foundation and World Wide Fund for Nature Brazil.Araguaian botos (Inia araguaiaensis) are known to produce pulsed as well as tonal sounds. This study documents the first evidence for repetitive sequences of downsweep whistles in botos that appear to be shared between individuals, and the context of their occurrence is investigated. Boat surveys were conducted along the Tocantins River located in the Eastern Amazon over a period of 42 days between 2012 and 2018. Eighty-two groups of Araguaian botos were observed, and 43 h of sound recordings were acquired. 632 downsweep whistles were recorded in 10 encounters. Four of these encounters contained downsweep bouts (21 bouts with ≥2 whistles) with short inter-call intervals (bout criterion 50 s) and up to 161 whistles. A statistical relationship was not found between downsweep occurrence and any of the contextual parameters that were investigated, including socializing, travelling, feeding, group size, presence of calves, and socio-sexual displays. The rarity of these signals makes them unlikely candidates for individual or group identification. It is more likely that they are associated with very specific contexts, such as nursing or mating, both of which were rarely observed in this study. Further studies are required to investigate context specificity and elucidate the function of these signals.PostprintPeer reviewe

DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway

DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3’end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that lack depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.This work was supported by Instituto Nacional de Saúde Doutor Ricardo Jorge and Fundação para a Ciência e a Tecnologia (FCT) [UID/MULTI/04046/2019 Research Unit Grant (to BioISI)]. Juan F. García-Moreno and Paulo J. da Costa were recipients of a fellowship from BioSys PhD programme (SFRH/BD/52495/2014, and PD/BD/142898/2018, respectively).info:eu-repo/semantics/publishedVersio

A pandemia de COVID-19 e seu efeito na estrutura do Brief-COPE

This study aimed to investigate the dimensional structure of Brief-COPE during the COVID-19 pandemic. Six hundred and sixty-six adults from all regions of Brazil, mostly women (77 %), aged between 18 and 79 years old (M = 36.70; SD = 13.12), took part in this research. They answered sociodemographic questions and the Brief-COPE. Descriptive and confirmatory factor analyzes were performed. The first order dimensional structure was confirmed with the 14 original factors. The second order structure did not converge, and a new second order structure was proposed based on the correlation indexes among the first order factors. The proposed new model presented adequate indexes of adjustment to the data. Such results suggest that the pandemic may have changed the way participants perceive and relate coping strategies.El presente estudio tuvo como objetivo investigar la estructura dimensional de Brief-COPE durante la pandemia de COVID-19. Seiscientos sesenta y seis adultos de todas las regiones de Brasil participaron en esta investigación, en su mayoría mujeres (77 %), con edades entre 18 y 79 años (M = 36.70; DE = 13.12). Los participantes respondieron preguntas sociodemográficas y el Brief-COPE. Se realizaron análisis descriptivos y análisis factoriales confirmatorios. Se confirmó la estructura dimensional de primer orden, con 14 factores. La estructura de segundo orden no convergió y se propuso una nueva estructura de segundo orden basada en la correlación entre los factores de primer orden. El nuevo modelo propuesto presentó índices adecuados de ajuste a los datos. Estos resultados sugieren que la pandemia puede haber cambiado la forma en que los participantes perciben y relacionan las estrategias de afrontamiento.O presente estudo teve como objetivo investigar a estrutura dimensional do Brief-COPE durante a pandemia de COVID-19. Participaram desta pesquisa 666 adultos de todas as regiões do Brasil, majoritariamente mulheres (77 %), com idade entre 18 e 79 anos (M = 36,70; DP = 13,12). Estes responderam perguntas sociodemográficas e o Brief-COPE. Foram realizadas análises descritivas e Análises Fatoriais Confirmatórias. A estrutura dimensional de primeira ordem foi confirmada, com 14 fatores. A estrutura de segunda ordem não convergiu, sendo proposta uma nova estrutura de segunda ordem tomando como base a correlação entre os fatores de primeira ordem. O novo modelo proposto apresentou índices adequados de ajuste aos dados. Tais resultados sugerem que a pandemia pode ter alterado a forma como os participantes percebem e relacionam as estratégias de enfrentamento

A comparison between preterm and full-term infants\u2019 preference for faces [Uma compara\ue7\ue3o entre rec\ue9m-nascidos prematuros e a termo na prefer\ueancia por faces]

Objective: Visual preference for faces at birth is the product of a multimodal sensory experience experienced by the fetus even during the gestational period. The ability to recognize faces allows an ecologically advantageous interaction with the social environment. However, perinatal events such as premature birth, may adversely affect the adequate development of this capacity. In this study, we evaluated the preference for facial stimuli in preterm infants within the first few hours after birth. Methods: This is a cross-sectional observational study of 59 newborns, 28 preterm and 31 full-term infants. The babies were assessed in the first hours of life, with two white boards in the shape of a head and neck: one with the drawing of a face similar to the human face (natural face), and one with the drawing of misaligned eyes, mouth and nose (distorted face). After the newborn fixated the eyes on the presented stimulus, it was slowly moved along the visual field. The recognition of the stimulus was considered present when the baby had eye or head movements toward the stimulus. Results: The preterm infants, in addition to showing a lower occurrence of orientation movements for both stimuli, on average (1.8 ± 1.1 to natural faces and 2.0 ± 1.2 for distorted ones) also showed no preference for any of them (p = 0.35). Full-term newborns showed a different behavior, in which they showed a preference for natural faces (p = 0.002) and a higher number of orientations for the stimulus, for both natural (3.2 ± 0.8) and distorted faces (2.5 ± 0.9). Conclusion: Preterm newborns recognize facial stimuli and disclose no preference for natural faces, different from full-term newborns. Resumo: Objetivo: A preferência visual por faces ao nascimento é produto de uma experiência sensorial multimodal vivenciada pelo feto ainda no período gestacional. A habilidade de reconhecer faces possibilita uma interação ecologicamente vantajosa com o ambiente social. Entretanto, eventos perinatais, como o nascimento prematuro, podem prejudicar o desenvolvimento adequado dessa habilidade. Nesse trabalho, avaliamos a preferência por estímulos faciais de recém-nascidos prematuros nas primeiras horas após o nascimento. Métodos: Trata-se de um estudo observacional transversal realizado com 59 recém-nascidos, 28 prematuros e 31 nascidos termos. Os bebês foram avaliados, nas primeiras horas de vida, com duas pranchas brancas em formato de cabeça e pescoço: uma com o desenho de uma face similar ao rosto humano (face natural), e outra com o desenho de olhos, boca e nariz desalinhados (face distorcida). Após o recém-nascido fixar o olhar no estímulo apresentado o mesmo era lentamente movimentado ao longo do campo visual. O reconhecimento do estímulo foi considerado presente quando o bebê apresentou movimentos dos olhos ou cabeça em direção ao estímulo. Resultados: Os recém-nascidos prematuros além de apresentarem menor ocorrência de movimentos de orientação para ambos os estímulos, em média (1,8 ± 1,1 para faces naturais e 2,0 ± 1,2 para faces distorcidas), também não apresentaram preferência por qualquer um deles (p = 0,35). Diferente foi o comportamento dos recém-nascidos a termo que apresentaram preferência por faces naturais (p = 0,002) e um número maior de orientações para o estímulo, tanto para faces naturais (3,2 ± 0,8) quanto para faces distorcidas (2,5 ± 0,9). Conclusão: Recém-nascidos prematuros reconhecem os estímulos faciais e não apresentam preferência por faces naturais, diferente de recém-nascidos a termos. Keywords: Model of visual recognition, Visual perception, Newborn, Preterm infant, Full-term infant, Palavras-chave: Reconhecimento visual de modelos, Percepção visual, Recém-nascido, Prematuro, Nascimento a term

Quantifying loopy network architectures

Biology presents many examples of planar distribution and structural networks having dense sets of closed loops. An archetype of this form of network organization is the vasculature of dicotyledonous leaves, which showcases a hierarchically-nested architecture containing closed loops at many different levels. Although a number of methods have been proposed to measure aspects of the structure of such networks, a robust metric to quantify their hierarchical organization is still lacking. We present an algorithmic framework, the hierarchical loop decomposition, that allows mapping loopy networks to binary trees, preserving in the connectivity of the trees the architecture of the original graph. We apply this framework to investigate computer generated graphs, such as artificial models and optimal distribution networks, as well as natural graphs extracted from digitized images of dicotyledonous leaves and vasculature of rat cerebral neocortex. We calculate various metrics based on the Asymmetry, the cumulative size distribution and the Strahler bifurcation ratios of the corresponding trees and discuss the relationship of these quantities to the architectural organization of the original graphs. This algorithmic framework decouples the geometric information (exact location of edges and nodes) from the metric topology (connectivity and edge weight) and it ultimately allows us to perform a quantitative statistical comparison between predictions of theoretical models and naturally occurring loopy graphs.Comment: 17 pages, 8 figures. During preparation of this manuscript the authors became aware of the work of Mileyko at al., concurrently submitted for publicatio

Investigação sorológica de espécies de Ehrlichia em cães, equinos e humanos de um assentamento rural do sul do Brasil

Objetivou-se determinar a soroprevalência de Ehrlichia spp. e os fatores de risco associados a exposição em uma população restrita de cães, cavalos e humanos altamente expostos a picadas de carrapatos em um assentamento rural brasileiro utilizando um teste comercial de ELISA rápido e dois testes de imunofluorescência indireta (IFI) com antígenos brutos de E. canis e E. chaffeensis. Amostras de soro de 132 cães, 16 cavalos e 100 humanos foram utilizadas. Cinquenta e seis/132 (42,4%) cães foram soropositivos para E. canis. Cães > um ano apresentaram mais chance de serem soropositivos para E. canis do que cães ≤ um ano (p =0,0051). Dez/16 (62,5%) e 8/16 (50%) cavalos foram soropositivos pelo ELISA comercial e IFI, respectivamente. Cinco/100 (5%) humanos foramsoropositivos para E. canis e E. chaffeensis. Rhipicephalus sanguineus (n= 291, 97,98%) nos cães e A. cajennense (n = 25, 96,15%) nos cavalos foram os carrapatos mais encontrados. Concluindo, anticorpos anti-Ehrlichia spp. foram encontrados em cavalos; entretanto, a ausência de uma caracterização molecular impede qualquer conclusão sobre agente envolvido. Além disso, a alta soroprevalência de E. canis em cães e a evidência de anticorpos anti-Ehrlichia sp. em humanos, sugere que os casos de erliquiose humana no Brasil possam ser causados por E. canis ou outra espécie intimamente relacionada.The aims of this study were to determine the seroprevalence of Ehrlichia spp. and risk factors for exposure in a restricted population of dogs, horses, and humans highly exposed to tick bites in a Brazilian rural settlement using a commercial ELISA rapid test and two indirect immunofluorescent assays (IFA) with E. canis and E. chaffeensis crude antigens. Serum samples from 132 dogs, 16 horses and 100 humans were used. Fifty-six out of 132 (42.4%) dogs were seropositive for E. canis. Dogs > one year were more likely to be seropositive for E. canis than dogs ≤ one year (p = 0.0051). Ten/16 (62.5%) and 8/16 (50%) horses were seropositive by the commercial ELISA and IFA, respectively. Five out of 100 (5%) humans were seropositive for E. canis and E. chaffeensis. Rhipicephalus sanguineus (n = 291, 97.98%) on dogs and Amblyomma cajennense (n = 25, 96.15%) on horses were the most common ticks found. In conclusion, anti-Ehrlichia spp. antibodies were found in horses; however, the lack of a molecular characterization precludes any conclusion regarding the agent involved. Additionally, the higher seroprevalence of E. canis in dogs and the evidence of anti-Ehrlichia spp. antibodies in humans suggest that human cases of ehrlichiosis in Brazil might be caused by E. canis, or other closely related species

Percutaneous vs. surgical treatment of patent ductus arteriosus in children and adolescents

INTRODUÇÃO: Estudos comparando os métodos percutâneo e cirúrgico no tratamento da persistência do canal arterial (PCA) são raros na literatura. Nosso objetivo foi realizar análise comparativa entre os dois métodos de tratamento da PCA, enfatizando os aspectos de eficácia e morbidade. MÉTODOS: Estudo observacional com 2 coortes de crianças e adolescentes &gt; 5 kg e < 14 anos, portadores de PCA, tratados durante um projeto de avaliação de incorporação de novas tecnologias ao Sistema Único de Saúde (SUS), realizado em um hospital cardiológico de excelência, em parceria com o Ministério da Saúde do Brasil. Foi feita análise prospectiva no grupo percutâneo entre 2009 e 2011 e retrospectiva no grupo cirúrgico entre 2006 e 2011. RESULTADOS: Foram incluídos 80 pacientes no grupo percutâneo (60% do sexo feminino) e 39 no grupo cirúrgico (51% do sexo feminino; P = 0,37). A mediana de idade e de peso dos grupos percutâneo e cirúrgico foi de 39,4 meses vs. 25,5 meses (P = 0,04) e de 14 kg vs. 11,1 kg (P = 0,052), respectivamente. No grupo percutâneo, 78 pacientes (92%) tinham PCA do tipo A e o diâmetro mínimo do canal à angiografia foi de 2,5 ± 1,2 mm. As próteses mais utilizadas foram Amplatzer®, molas de Gianturco e CeraTM. A técnica cirúrgica mais utilizada foi a clipagem. A taxa de sucesso dos procedimentos foi de 100% nos dois grupos. O grupo cirúrgico apresentou maiores taxas de complicação, incluindo quilotórax, infecções, necessidade de hemoderivados, hipertensão arterial sistêmica e uso de opioides, como também maior necessidade de terapia intensiva. A mediana do tempo de internação foi de 1,3 dia no grupo percutâneo e de 7,9 dias no grupo cirúrgico (P < 0,01). À alta hospitalar, as taxas de oclusão foram semelhantes nos dois grupos (91% no grupo percutâneo e 87% no grupo cirúrgico; P = 0,71). CONCLUSÕES: Em decorrência da menor morbidade, do menor tempo de internação e da igual eficácia, o tratamento percutâneo da PCA deve ser considerado a modalidade terapêutica de escolha para pacientes selecionados

Phenotypic and Functional Signatures of Peripheral Blood and Spleen Compartments of Cynomolgus Macaques Infected With T. cruzi: Associations With Cardiac Histopathological Characteristics

We performed a detailed analysis of immunophenotypic features of circulating leukocytes and spleen cells from cynomolgus macaques that had been naturally infected with Trypanosoma cruzi, identifying their unique and shared characteristics in relation to cardiac histopathological lesion status. T. cruzi-infected macaques were categorized into three groups: asymptomatic [CCC(-)], with mild chronic chagasic cardiopathy [CCC(+)], or with moderate chronic chagasic cardiopathy [CCC(++)]. Our findings demonstrated significant differences in innate and adaptive immunity cells of the peripheral blood and spleen compartments, by comparison with non-infected controls. CCC(+) and CCC(++) hosts exhibited decreased frequencies of monocytes, NK and NKT-cell subsets in both compartments, and increased frequencies of activated CD8+ T-cells and GranA+/GranB+ cells. While a balanced cytokine profile (TNF/IL-10) was observed in peripheral blood of CCC(-) macaques, a predominant pro-inflammatory profile (increased levels of TNF and IFN/IL-10) was observed in both CCC(+) and CCC(++) subgroups. Our data demonstrated that cardiac histopathological features of T. cruzi-infected cynomolgus macaques are associated with perturbations of the immune system similarly to those observed in chagasic humans. These results provide further support for the validity of the cynomolgus macaque model for pre-clinical research on Chagas disease, and provide insights pertaining to the underlying immunological mechanisms involved in the progression of cardiac Chagas disease