hybridModels: An R Package for the Stochastic Simulation of Disease Spreading in Dynamic Networks

Disease spreading simulations are traditionally performed using coupled differential equations. However, in the setting of metapopulations, most of the solutions provided by this method do not account for the dynamic topography of subpopulations. Conversely, the alternative approach of individual-based modeling (IBM) may add computational cost and complexity. Hybrid models allow for the study of disease spreading because they combine both aforementioned approaches by separating them across different scales: a local scale that addresses subpopulation dynamics using coupled differential equations and a global scale that addresses the contact between these subpopulations using IBM. We present a simple way of simulating the spread of disease in dynamic networks using the high-level statistical computational language R and the hybridModels package. We built four examples using disease spread models at the local scale in several different networks: an animal movement network; a three-node network, whose model solution using a stochastic simulation algorithm is compared with the ordinary differential equations approach; the commuting of individuals between patches, which we compare with the permanent migration of individuals; and the commuting of individuals within the metropolitan area of São Paulo

Assessment of Methane Production by Goats under Intermittent Grazing

There are 875 million goats worldwide (FAO 2012) and the majority are in developing countries where they are typically raised on pasture. Ruminants release gross energy as methane, which is a greenhouse gas. Mthane mitigation strategies require prior knowledge about emission of methane by animals under different management systems. Intake, quality and type of feed are factors that influence methane emissions, therefore the objective of this study was to investigate how grazing intensity, measured by the residual leaf area index (RLAI), influences methane emission by goats under rotational grazing on Tanzania grass pasture

Leishmania amazonensis promastigotes in 3D Collagen I culture: an in vitro physiological environment for the study of extracellular matrix and host cell interactions

Leishmania amazonensis is the causative agent of American cutaneous leishmaniasis, an important neglected tropical disease. Once Leishmania amazonensis is inoculated into the human host, promastigotes are exposed to the extracellular matrix (ECM) of the dermis. However, little is known about the interaction between the ECM and Leishmania promastigotes. In this study we established L. amazonensis promastigote culture in a three-dimensional (3D) environment mainly composed of Collagen I (COL I). This 3D culture recreates in vitro some aspects of the human host infection site, enabling the study of the interaction mechanisms of L. amazonensis with the host ECM. Promastigotes exhibited “freeze and run” migration in the 3D COL I matrix, which is completely different from the conventional in vitro swimming mode of migration. Moreover, L. amazonensis promastigotes were able to invade, migrate inside, and remodel the 3D COL I matrix. Promastigote trans-matrix invasion and the freeze and run migration mode were also observed when macrophages were present in the matrix. At least two classes of proteases, metallo- and cysteine proteases, are involved in the 3D COL I matrix degradation caused by Leishmania. Treatment with a mixture of protease inhibitors significantly reduced promastigote invasion and migration through this matrix. Together our results demonstrate that L. amazonensis promastigotes release proteases and actively remodel their 3D environment, facilitating their migration. This raises the possibility that promastigotes actively interact with their 3D environment during the search for their cellular “home”—macrophages. Supporting this hypothesis, promastigotes migrated faster than macrophages in a novel 3D co-culture model

Investigation of human papillomavirus by hybrid capture II in cervical carcinomas including 113 adenocarcinomas and related lesions

Hybrid capture is an easy and highly sensitive technique for screening population due to its capacity to detect malignant and premalignant lesions of the cervix. To evaluate its ensitivity, we investigated the frequency of high-risk human papillomavirus (HPV) infection and its correlation with glandular malignant lesions, analyzing a total of 113 cases of adenocarcinomas and related lesions. High-risk HPV was investigated using a hybrid capture II (HC2) assay. Samples were collected in two different ways: either brushed directly from surgical specimens before fixation or collected from the patients. We also investigated the frequency of HPV in squamous malignant lesions, 65 squamous cell carcinomas (SCC) and 66 in situ squamous cell carcinomas (ISSCC), to compare the occurrence of HPV for these lesions. The 113 glandular lesions comprised 62 invasive adenocarcinomas (IAC), 8 in situ adenocarcinomas (ISAC), 26 IAC plus SCC, and 17 adenosquamous cells carcinomas (ASCC). The HPV-positive reactions were as follows: 51 (82.2%) in IAC, 8 (100%) in ISAC, 25 (96.1%) in IAC plus SCC, and 14 (82.3%) in ASCC. HC2-positive results in the squamous malignant lesions were as follows: 58 of 63 (89.0%) for SCC and 94 of 103 (91.2%) for ISSCC. High-risk HPV infection was quite similar for glandular and pure squamous invasive malignant lesions, 82.2% and 89.0%, respectively, indicating that high-risk HPV is also highly prevalent in glandular lesions. Although hybrid capture proved to be an excellent adjunctive technique, we do not believe its results merit replacing the Pap smear as a screening tool

Climate-induced variability in South Atlantic wave direction over the past three millennia.

ABSTRACT: Through alteration of wave-generating atmospheric systems, global climate changes play a fundamental role in regional wave climate. However, long-term wave-climate cycles and their associated forcing mechanisms remain poorly constrained, in part due to a relative dearth of highly resolved archives. Here we use the morphology of former shorelines preserved in beach-foredune ridges (BFR) within a protected embayment to reconstruct changes in predominant wave directions in the Subtropical South Atlantic during the last ~3000 years. These analyses reveal multi-centennial cycles of oscillation in predominant wave direction in accordance with stronger (weaker) South Atlantic mid- to high-latitudes mean sea-level pressure gradient and zonal westerly winds, favouring wave generation zones in higher (lower) latitudes and consequent southerly (easterly) wave components. We identify the Southern Annular Mode as the primary climate driver responsible for these changes. Long-term variations in interhemispheric surface temperature anomalies coexist with oscillations in wave direction, which indicates the influence of temperature-driven atmospheric teleconnections on wave-generation cycles. These results provide a novel geomorphic proxy for paleoenvironmental reconstructions and present new insights into the role of global multi-decadal to multi-centennial climate variability in controlling coastal-ocean wave climate.A.P.S. and A.H.F.K. acknowledge the Brazilian Ministry of Environment for funding through the SMC-Brazil project. A.H.F.K. acknowledges the Rede Clima, INCT MarCOI “Oceanografia Integrada e Usos Multiplos da Plataforma Continental e Oceano Adjacente—Centro de Oceanografia Integrada (COI)”, CNPQ (PQ2- CNPQ 301963/2015-0, PQ1D CNPQ 301597/2018-9, CNPQ 441545/2017-3) and, CAPES Brazil-Finance Code 001 and Capes/PROEX 88881.146046/2017-01 for financial support. F.J.M. acknowledges the funding from the Spanish Ministry of Science and Innovation through the project PID2019-107053RB-I00. A.P.S. acknowledges the CESM1(CAM5) Last Millennium Ensemble Community Project and supercomputing resources provided by NSF/CISL/Yellowstone. C.J.H. acknowledges that this paper is Contribution 3957 of the Virginia Institute of Marine Science, William & Mary

Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast

Metaplastic carcinomas of the breast (MCBs) are unusual neoplasms characterized by an admixture of glandular epithelial components, which frequently exhibit features of squamous differentiation, and mesenchymal malignant components. Regardless of the presence of myoepithelial features in MCB, no consensus concerning their putative histogenesis has yet been achieved. Recently, novel putative myoepithelial markers have been developed, including p63, maspin, and P-cadherin. We assessed the expression of these myoepithelial markers in MCBs and compared their expression with classic myoepithelial markers. Immunohistochemistry using the streptavidin– biotin–peroxidase complex technique with antibodies raised against p63, maspin, P-cadherin, actin (clones CGA7, 1A4 and HHF35), cytokeratin 14 (Ck14), and vimentin was performed on 16 MCBs (7 matrix-producing MCBs, 6 adenosquamous MCBs, and 3 MCBs with heterologous elements). In healthy breast lobules and ducts adjacent to the tumors, myoepithelial cells showed distinctive and consistent immunoreactivity for p63, maspin, P-cadherin, actin, S-100 protein, and Ck14. Matrix- producing MCBs were positive for maspin in all cases, for p63 in 4 of 7 cases, and for P-cadherin in 4 of 7 cases. Adenosquamous MCB showed immunoreactivity for p63, maspin, and P-cadherin in 5 of 6 cases. All novel myoepithelial markers and Ck14 decorated squamous cell islands. MCBs with heterologous elements were positive for p63 in 1 case, for maspin in all 3 cases, and for P-cadherin in 2 cases. All cases showed at least one of the novel myoepithelial markers. Eleven of 16 cases were positive for actin. Eleven of 14 cases reacted with Ck14, and all cases that stained for S-100 protein (9 of 9) and vimentin (13 of 13) were also positive. Based on our findings, the balance of probabilities favors that MCBs may have a basal or myoepithelial cell histogenesis and differentiation.Fundacão para a Ciência e a Tecnologia (FCT), Ministério da Ciência e Tecnologia (MCT) - SFRH/BD/5386/2001

CYTOTOXICITY, ANTI-POLIOVIRUS ACTIVITY AND IN SILICO BIOLOGICAL EVALUATION OF CONSTITUENTS FROM MAYTENUS GONOCLADA (CELASTRACEAE)

Objective: The in silico free access web tools PASS online and ChemMapper were used to predict potential biological activities of compounds 1 to 8 isolated from Maytenus gonoclada (Celastraceae). The constituents 4'-O-methylepigalocatequin (6), tingenone (7) and proanthocyanidin A (8), and ethanolic extracts were subjected to in vitro cytotoxicity using VERO cells and anti-Poliovirus assays. Methods: QSAR and molecular superposition, correlating the average number of pharmacophores were used in the prediction studies. Cellular line VERO ATCC CCL-81 was used to determine anti-Poliovirus effect, observed by colorimetric (MTT) method. The annexing V/propidium iodide assay was used to determine the occurrence of apoptosis in the cytotoxicity assays. Results: The experimental results found for constituents 6-8 were in accordance with observed data obtained through PASS online and ChemMapper simulation. Conclusion: Compound 7 showed higher cytotoxic and apoptosis induction properties, and 6 and 8 presented anti-Poliovirus activity

Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.CP received a PhD fellowship from Fundacao para a Ciencia e Tecnologia (SFRH/BD/27465/2006)

PRODUCTION AND PRODUCTIVITY POTENTIAL OF EIGHT STRAWBERRY CULTIVARS UNDER HIGH TEMPERATURE

O morangueiro requer mão-de-obra qualificada e bastantes cuidados em seu manejo. O cultivo dessa fruta no Brasil ocorre, principalmente nos estados do Sul e Sudeste do país. Na região Nordeste do país pouco se planta, principalmente em Pernambuco, devido principalmente ao clima. Esta fruta que apresenta grande retorno financeiro gerando empregos e divisas para estados e municípios. A descoberta de locais propícios ao cultivo poderá gerar maior desenvolvimento local. Visando expansão da fronteira agrícola do morango, neste trabalho objetivou-se avaliar a cultivar mais adaptada a Região Metropolitana do Recife. Foram testadas 8 cultivares de morangueiro com 8 repetições. Avaliou-se a emissão de estolhos e produtividade para a seleção da cultivar mais adaptada ao clima quente e úmido. As estimativas de produtividade de todos os tratamentos estiveram abaixo da média nacional para o cultivo do morangueiro, fator que se deve ao plantio em época quente