In situ loading and delivery of short single- And double-stranded dna by supramolecular organic frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double endlabeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF-nucleic acid ratios. In addition to high delivery efficiencies, the watersoluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery

Pseudo-static tests of terminal stirrup-confined concrete-filled rectangular steel tubular columns

© 2017 Elsevier Ltd This paper mainly presents a pseudo-static test program on 12 terminal stirrup-confined square concrete-filled steel tube (SCFT) columns and 14 rectangular SCFT columns under constant axial pressure. The effects of various factors on the hysteretic behavior of specimens are investigated. These factors include with or without stirrups, height of terminal stirrup region, equivalent stirrup ratio, stirrup form, loading direction, height-length ratio (L/B), length-width ratio (B/D), axial compression ratio (n) and sliding support. The failure mode, strain ratio, hysteretic curve, skeleton curve, ultimate bearing capacity, ductility, stiffness degradation, energy dissipation, as well as the residual deformation of the specimens are analyzed. The results indicate that: (1) When n is relatively larger, the bidirectional stirrups can effectively delay the local buckling of steel tube and greatly increase the ultimate bearing capacity, stiffness, equivalent damping viscosity index, residual deformation rate and ductility index, and further significantly improve the seismic behavior of the rectangular SCFT columns; (2) Axial pressure can improve the confinement effect from the steel tube to the core concrete, also bidirectional stirrups can directly confine the core concrete to decrease strain ratio of the steel tube; (3) With the same value of n, increasing the height of terminal stirrup region or increasing the equivalent stirrup ratio can effectively improve the seismic behavior of the rectangular SCFT columns; (4) The influence of loading direction, L/B and B/D on the ductility of rectangular SCFT columns are not obvious

Alternativas en camino en Foz de Iguazú: pensando una educación para los derechos humanos y el territorio

Anais do IV Encontro de Iniciação Científica da Unila - “UNILA 5 anos: Integração em Ciência, Tecnologia e Cultura na Tríplice Fronteira” - 05 e 06 de novembro de 2015 – Sessão Ciência Política, Sociologia, Filosofia e AntropologiaEste artículo se propone realizar un análisis de los impactos que pudó haber generado el desarrollo del proyecto de extensión “Educación para la Ciudadanía y el Territorio”, durante el año 2014 en el Colegio Estadual Gustavo Dobradinho, en el barrio de Porto Meira, Foz do Iguazú. El proyecto fue desarrollado por estudiantes y docentes de la Universidad Federal de la Integración Latinoamericana en las dos turmas del 3 er año, tanto matutino como nocturno. Para conseguir detectar impactos del proyecto y analizarlos, objetivos de esta investigación, utilizaremos como fuente de análisis nuestro diario de campo etnográfico, entrevistas y cuestionarios realizados a los/as educandos/as, educadores/as y a la directora del Colegio. También buscaremos demostrar la importancia de trabajar conceptos como el de derechos humanos, territorio y educación especialmente en escuelas públicas con contexto socio- económico vulnerable, considerandolo como mecanismo de empoderamiento de los sectores populares. Entendemos que es a partir de ese tipo de procesos que se puede llegar a una mayor participación popular en los procesos de decisión política, económica y social que visan la garantía y efectivación de derechos. Destacamos la importancia del proyecto de extensión al haber abordado tematicas como participación política, derecho a la ciudad, a la moradia, al transporte, en un contexto de elecciones nacionales y de proximas remociones habitacionales en el barrio. Este trabajo es sudivido en tres partes. En primer lugar encontrarán “Globalización, neoliberalismo y problemáticas urbanas” dónde se realiza una breve contextualización de los procesos urbanos desarrollados en Brasil en los últimos años desde la implantación de las políticas neoliberales dentro de la dinámica nacional – internacional. También se estudia, en esa primera parte, el barrio y el contexto de la Triple Frontera - donde se desarrolló el proyecto de extensión “Educación para la Ciudadanía y el territorio” – dentro de dichos procesos urbanos. La segunda subdivisión, llamada “Prácticas que construyen alternativas: educando para la participación popular”, es dedicada al estudio de los impactos de la acción de extensión tanto en la escuela como en el cotidiano de los/as educando que participaron. Por último, a modo de reflexión acerca de la investigación y sus resultados, están las Consideraciones Finales. Agradecemos al Conselho Nacional de Pesquisa - CNPQ por la bolsa/beca de iniciación científica concedida.Bolsista del Programa PROBIC UNILA 2014/2015 / Bolsa financiada por la CNP

Extracts of Feijoa Inhibit Toll-Like Receptor 2 Signaling and Activate Autophagy Implicating a Role in Dietary Control of IBD

Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory disease affecting the gut with limited treatment success for its sufferers. This suggests the need for better understanding of the different subtypes of the disease as well as nutritional interventions to compliment current treatments. In this study we assess the ability of a hydrophilic feijoa fraction (F3) to modulate autophagy a process known to regulate inflammation, via TLR2 using IBD cell lines

Automated quantification of mitral valve anatomy using anatomical intelligence in three-dimensional echocardiography

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The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Antagonism of Host Antiviral Responses by Kaposi's Sarcoma-Associated Herpesvirus Tegument Protein ORF45

Virus infection of a cell generally evokes an immune response by the host to defeat the intruder in its effort. Many viruses have developed an array of strategies to evade or antagonize host antiviral responses. Kaposi's sarcoma-associated herpesvirus (KSHV) is demonstrated in this report to be able to prevent activation of host antiviral defense mechanisms upon infection. Cells infected with wild-type KSHV were permissive for superinfection with vesicular stomatitis virus (VSV), suggesting that KSHV virions fail to induce host antiviral responses. We previously showed that ORF45, a KSHV immediate-early protein as well as a tegument protein of virions, interacts with IRF-7 and inhibits virus-mediated type I interferon induction by blocking IRF-7 phosphorylation and nuclear translocation (Zhu et al., Proc. Natl. Acad. Sci. USA. 99:5573-5578, 2002). Here, using an ORF45-null recombinant virus, we demonstrate a profound role of ORF45 in inhibiting host antiviral responses. Infection of cells with an ORF45-null mutant recombinant KSHV (BAC-stop45) triggered an immune response that resisted VSV super-infection, concomitantly associated with appreciable increases in transcription of type I IFN and downstream anti-viral effector genes. Gain-of-function analysis showed that ectopic expression of ORF45 in human fibroblast cells by a lentivirus vector decreased the antiviral responses of the cells. shRNA-mediated silencing of IRF-7, that predominantly regulates both the early and late phase induction of type I IFNs, clearly indicated its critical contribution to the innate antiviral responses generated against incoming KSHV particles. Thus ORF45 through its targeting of the crucial IRF-7 regulated type I IFN antiviral responses significantly contributes to the KSHV survival immediately following a primary infection allowing for progression onto subsequent stages in its life-cycle

Histone Acetylation-Mediated Regulation of the Hippo Pathway

The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al