Characterization of BK viral responses to the dual-PI3K/MTOR inhibitor dactolisib (NVP BEZ-235) in a renal cell culture model

BK virus (BKV) is a ubiquitous polyomavirus known to asymptomatically reside in the renal tissues of up to 90% of the human population. BK virions reactivate during periods of intense immunosuppression and can cause disease in renal transplant recipients, such as BKV-associated nephropathy (BKVAN). BKVAN can lead to loss of the transplanted renal grafts. For this reason, the study of BKV biology is of importance to the transplant community. Previous studies have shown that BKV upregulates the pro-growth mTOR pathway in host cells, thereby increasing BKV replicative efficiency. Downstream effectors of the mTOR pathway, particularly p70S6 kinase, control the basal rate of protein translation, in part through regulation of ribosomal biogenesis. It was hypothesized that viral upregulation of the mTOR pathway is beneficial for viral replication due to an increase in the number of ribosomes available to translate viral proteins. Therefore, inhibition of the mTOR pathway could reduce viral replication. This study investigated whether host cell mTOR inhibition could reduce BK viral replication in an in vitro model. We utilized the dual PI3K/mTOR inhibitor NVP BEZ-235 (Novartis Pharmaceuticals), which potently downregulates expression of both upstream (PI3K) and central (mTOR) effectors of the mTOR pathway. Immortalized renal epithelial cells were exposed to varying concentrations of BEZ-235 for a period of 48 hours, infected with BK virus for three hours, and allowed to grow for a further 48 hours. Cell populations were then assayed via quantitative PCR (qPCR), Western blotting and fluorescent immunohistochemical staining to determine the effect of BEZ-235 on BK viral replication. Western blot experiments confirmed the effectiveness of BEZ-235's inhibition of the mTOR pathway in a renal epithelial cell culture model, as well as downregulation of the mTOR pathway during BK viral infection. Western blotting for the key BK replicative protein Large T antigen showed a dose-dependent decrease in expression, with increasing concentrations of BEZ-235. Fluorescent immunohistochemical staining showed a dose-dependent decrease in expression of Large T antigen staining in host cell nuclei. qPCR results were inconclusive, in that no clear pattern in the number of BKV genomes per cell population could be observed across the range of BEZ-235 concentrations tested. While results from our study indicate that BEZ-235 can reduce BKV replication in vitro, further in vitro experimentation, including repetition of approaches already carried out as well as novel approaches, will be needed to definitively confirm inhibition of the mTOR pathway as a viable antiviral strategy

The Need for Social Work Advocacy to Create Social Justice for Transgender People: A Call to Action

Transgender people in the United States experience high levels of employment discrimination. The Employment Nondiscrimination Act (ENDA) is one mechanism that would provide basic workplace protections for this population. We argue, however, that passage of ENDA is only one of many preliminary steps to help transgender people experience an essential basic version of social justice. Using Bonnycastle\u27s (2011) social justice relational illustrative model, we develop a conceptual framework that argues that social workers need to advocate for transgender people on a policy level in order to move them from their current nonexistent version of social justice to a basic version of social justice. Recommendations are provided on how social work advocacy can help create this this basic version of social justice

Cómo el enseñar teoría ética y política podría ayudar a resolver dos de los mayores problemas de la profesión legal

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Ciclo de videoconferencias

Este cuadernillo reúne siete videoconferencias realizadas en el Marco de Cátedra Abierta: Ciclo de Videoconferencias llevadas a cabo por el Observatorio Argentino de Violencia en las Escuelas. Se exponen las videoconferencias de En este material encontrarán las videoconferencias de Beatriz Greco, Luis Alberto Quevedo, Rossana Reguillo Cruz, Esther Díaz, Perla Zelmanovich, Gabriel Noel, Marcela Gutiérrez y Daniel Bastán

Simple Microcontact Printing Technique to Obtain Cell Patterns by Lithography Using Grayscale, Photopolymer Flexographic Mold, and PDMS

Microcontact printing using PDMS embossing tools and its variations have aroused the interest of a wide spectrum of research fields, hence the feasibility of defining micro and nanoscale patterns. In this work, we have proposed and demonstrated a novel lithography method based on grayscale patterns printed in a flexographic photopolymer mold and transferred to epoxy resin and a single PDMS stamp to obtain different microprint pattern structures. The geometry of the patterns can be modified by adjusting the layout and grayscale of the stamp patterns. The functionality of this contact printing methodology was validated by generating human induced pluripotent stem cells (hiPSC) patterns. These specific micropatterns can be very useful for achieving complex differentiation in cell lines such as hiPSC. Microfabrication through the new technique provides a promising alternative to conventional lithography for constructing complex aligned surfaces; these structures could be used as components of biological patterns or microfluidic devices.Fil: Gimenez, Rocio. Universidad Tecnológica Nacional; ArgentinaFil: Pérez Sosa, Camilo José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional; ArgentinaFil: Bourguignon, Natalia. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bhansali, Shekhar. University of Florida; Estados UnidosFil: Arroyo, Carlos R.. Universidad de Las Fuerzas Armadas; EcuadorFil: Debut, Alexis. Universidad de Las Fuerzas Armadas; EcuadorFil: Lerner, Betiana. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perez, Maximiliano Sebastian. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

GRAVIDADE DOS CORPOS CELESTES

Gravidade é uma aceleração que comanda o movimento dos objetos celestes, quanto maior a massa e menor o raio de um corpo maior a sua gravidade. O objetivo do nosso trabalho é dispor informações sobre a gravidade em outros planetas, e curiosidades como a altura máxima que uma pessoa alcançar ao realizar um salto em deferentes planetas, assim como o tempo que permanecerá no ar durante o salto. Como metodologia pretende-se mostrar teoricamente ao espectador e comprovar por meio de cálculos, a variação da gravidade nos diferentes planetas, fazê-los refletir que peso não é sinônimo de massa, comentar sobre os diferentes pesos para uma mesma massa em diferentes corpos celestes e de que maneira a aceleração da gravidade interfere nos saltos e tempo de permanência de não contato com a superfície. Como resultados, espera-se que ao interagir com o público, voluntários participem informando seu peso aqui na Terra, para realizar as simulações oferecidas nesse trabalho em outros corpos celestes. Assim, por meio de cálculos realizados obteremos a altura e o tempo de salto da respectiva pessoa. Esses são os respectivos dados utilizados nos cálculos durante a apresentação: Sol, 274,13m/s²; Mercúrio, 3,7m/s²; Vênus, 8,87m/s²; Terra, 9,807m/s²; Lua, 1,622m/s²; Marte, 3,711 m/s²; Júpiter, 24,79 m/s²; Europa (Lua de Júpiter), 1,315 m/s²; Saturno, 10,44 m/s²; Urano, 8,69 m/s²; Netuno, 11,15 m/s²; Plutão, 0,62m/s². Por fim, é interessante ressaltar que existe uma outra teoria que explica o movimento dos corpos celestes, a relatividade geral de Abert Einstein. No entanto essa teoria não invalida a gravitação universal de Newton, ela complementa. Para campos gravitacionais relativamente pequenos a gravitação universal funciona perfeitamente. Ou seja, não é necessário utilizar-se das equações de Einstein para lançar um objeto na orbita da terra ou pra estudar a órbita da Estação Espacial Internacional (ISS). A relatividade geral vai ser essencial onde a gravitação universal tem seus limites, por exemplo, um buraco negro. O que Einstein fez foi explicar a origem da força gravitacional e não invalidar a existência dela. Dessa maneira, a gravidade apresenta-se como um tema relevante e atraente, fato que nos levou a escolhê-lo como tema desse trabalho

Atuação do tratamento odontológico em pacientes acometidos por câncer de cabeça e pescoço

O presente relato de experiência trata-se de um projeto de extensão do Curso de Odontologia, denominado “Suporte Odontológico Preventivo e Restaurador ao Paciente Oncológico (SOPRO)”, da Universidade Federal de Uberlândia, cujo objetivo é ampliar os cuidados orais preventivos e restauradores, assim como minimizar as complicações e/ou sequelas bucais de pacientes diagnosticados com câncer na região da cabeça e do pescoço submetidos ao tratamento oncológico, a fim de proporcionar a esses pacientes uma melhor qualidade de vida. Foram realizados atendimentos odontológicos todas as quartas-feiras, execução de procedimentos restauradores, orientações de saúde bucal e acompanhamento dos pacientes. 23 pacientes participaram do projeto durante o PEIC 2022. As ações foram desenvolvidas na instituição, na clínica odontológica do bloco 4T, no período de janeiro a dezembro de 2022. As atividades de extensão desse projeto permitiram interações entre graduandos e graduados em Odontologia e pacientes com diagnóstico de câncer de cabeça e pescoço em tratamento oncológico, o que contribuiu na formação profissional dos alunos participantes em relação aos cuidados e acompanhamento dos casos orientados no projeto

GEMA—An Automatic Segmentation Method for Real-Time Analysis of Mammalian Cell Growth in Microfluidic Devices

Nowadays, image analysis has a relevant role in most scientific and research areas. This process is used to extract and understand information from images to obtain a model, knowledge, and rules in the decision process. In the case of biological areas, images are acquired to describe the behavior of a biological agent in time such as cells using a mathematical and computational approach to generate a system with automatic control. In this paper, MCF7 cells are used to model their growth and death when they have been injected with a drug. These mammalian cells allow understanding of behavior, gene expression, and drug resistance to breast cancer. For this, an automatic segmentation method called GEMA is presented to analyze the apoptosis and confluence stages of culture by measuring the increase or decrease of the image area occupied by cells in microfluidic devices. In vitro, the biological experiments can be analyzed through a sequence of images taken at specific intervals of time. To automate the image segmentation, the proposed algorithm is based on a Gabor filter, a coefficient of variation (CV), and linear regression. This allows the processing of images in real time during the evolution of biological experiments. Moreover, GEMA has been compared with another three representative methods such as gold standard (manual segmentation), morphological gradient, and a semi-automatic algorithm using FIJI. The experiments show promising results, due to the proposed algorithm achieving an accuracy above 90% and a lower computation time because it requires on average 1 s to process each image. This makes it suitable for image-based real-time automatization of biological lab-on-a-chip experiments.Fil: Isa Jara, Ramiro Fernando. Escuela Superior Politécnica de Chimborazo; Ecuador. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pérez Sosa, Camilo José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional; ArgentinaFil: Macote Yparraguirre, Erick Leonel. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Revollo Sarmiento, Natalia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones en Ingeniería Eléctrica "Alfredo Desages". Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras. Instituto de Investigaciones en Ingeniería Eléctrica "Alfredo Desages"; ArgentinaFil: Lerner, Betiana. Florida International University; Estados Unidos. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Delrieux, Claudio Augusto. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pérez, Maximiliano. Florida International University; Estados Unidos. Universidad de Buenos Aires; ArgentinaFil: Mertelsmann, Roland. Albert Ludwigs University of Freiburg; Alemani

Single cell transfection of human-induced pluripotent stem cells using a dropletbased microfluidic system

Microfluidic tools have recently made possible many advances in biological and biomedical research. Research in fields such as physics, engineering, chemistry and biology have combined to produce innovation in microfluidics which has positively impacted diverse areas such as nucleotide sequencing, functional genomics, single-cell studies, single molecules assays and biomedical diagnostics. Among these areas, regenerative medicine and stem cells have benefited from microfluidics since these tools have had a profound impact on their applications. In this study, we present a high-performance droplet-based system for transfecting individual human-induced pluripotent stem cells. We will demonstrate that this system has great efficiency in single cells and captured droplets, like other microfluidic methods but with lower cost. Moreover, this microfluidic approach can be associated with the PiggyBac transposase-based system to increase its transfection efficiency. Our results provide a starting point for subsequent applications in more complex transfection systems, single-cell differentiation interactions, cell subpopulations and cell therapy, among other potential applications.Fil: Pérez Sosa, Camilo José. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanluis Verdes, Anahi. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Waisman, Ariel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lombardi, Antonella. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rosero, Gustavo. Universidad Tecnológica Nacional; ArgentinaFil: la Greca, Alejandro Damián. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bhansali, Shekhar. Florida International University; Estados UnidosFil: Bourguignon, Natalia. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luzzani, Carlos Daniel. Fundacion P/la Lucha C/enferm.neurologicas Infancia. Instituto de Neurociencias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Neurociencias.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perez, Maximiliano Sebastian. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lerner, Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional; Argentin