Cellular Uptake and Nuclear Delivery of Recombinant Adenovirus Penton Base

AbstractAn Ad2 capsid component, the penton base, expressed as recombinant protein, was found to be capable of affecting the entire entry pathway of adenovirion in HeLa cells, i.e., cell attachment, endocytosis, vesicular escape, intracytoplasmic movement, and translocation through the nuclear pore complex. Data with pentamerization-defective mutants suggested that none of these successive steps depended upon penton base pentamer status, indicating that the peptide domains responsible for these functions were carried by the monomer. Observations performed with wild-type (WT) and an integrin-binding-site double-mutant (K288E340) suggested that the penton base could enter the cell via an alternative, RGD- and LDV-independent, pathway. Of three mutants that were found to be defective in nuclear addressing in insect cells, only one, W165H, was also altered in nuclear transport in HeLa cells. The other two, W119H and RRR547EQQ, showed a WT pattern of nuclear localization in HeLa cells, suggesting that the region including tryptophan-119 and the basic signal at position 547 did not act as a nuclear localization signal in the human cell context. The integrity of cellular structures and the cytoskeleton seemed to be required for the vectorial movement and nuclear import of WT penton base, as suggested by experiments using permeabilized HeLa cells, isolated nuclear membranes, and cytoskeleton-targeted drugs

Uso de dibujos por parte de niños pequeños en problemas de suma

Understanding addition concept is troublesome for many young children. For individuals who struggle in comprehending this abstract concept, alternative representation form may help address such difficulty. This paper explores the drawings created by young children (6 years old) in addition problem solving activities. The study employed case study research design involving six children (aged six years) in three preschool centres. Data collection included observation, informal interviews and analysis of drawings. The findings showed that young children created two types of drawing and that the processes involved in producing the visual representations had facilitated the children’s understanding of addition. The study implicated that young children’s creations of drawings is an important learning experience and could be best assisted by valuing and supporting the early development of children’s drawn mathematical representation.Comprender el concepto de suma es problemático para muchos niños pequeños. Para las personas que luchan por comprender este concepto abstracto, la forma de representación alternativa puede ayudar a abordar dicha dificultad. Este artículo explora los dibujos creados por niños pequeños (6 años) además de actividades para resolver problemas. El estudio empleó un diseño de investigación de estudio de caso que involucró a seis niños (de seis años) en tres centros preescolares. La recolección de datos incluyó observación, entrevistas informales y análisis de dibujos. Los hallazgos mostraron que los niños pequeños crearon dos tipos de dibujos y que los procesos involucrados en la producción de las representaciones visuales habían facilitado la comprensión de la suma de los niños. El estudio implicaba que las creaciones de dibujos de los niños pequeños son experiencias de aprendizaje importantes y podrían ser mejor asistidas valorando y apoyando el desarrollo temprano de la representación matemática dibujada de los niños

Prevention and management of adverse events related to regorafenib

Regorafenib is an oral multikinase inhibitor that has shown antitumor activity in a range of solid tumors. Based on data from phase III clinical trials, regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, other available therapies, and in patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other appropriate treatments. A panel of oncology nurses, research coordinators, and other medical oncology experts, experienced in the care of patients treated with regorafenib, met to discuss the best practice for the management of regorafenib-associated adverse events (AEs). The panel agreed that, in clinical trials and daily practice with regorafenib, AEs are common but mostly manageable. The most common and/or important AEs associated with regorafenib were considered to be hand-foot skin reaction, rash or desquamation, stomatitis, diarrhea, hypertension, liver abnormalities, and fatigue. This manuscript describes the experience and recommendations of the panel for managing these AEs in everyday clinical practice. Appropriate education, monitoring, and management are considered essential for reducing the incidence, duration, and severity of regorafenib-associated AEs. © 2013 The Author(s)

Multi Inang Fungi Ektomikoriza pada Dipterocarpaceae di Hutan Tropis

Dipterocarpaceae dikenal sebagai keluarga vegetasi hutan dominan di hutan tropis yang memiliki simbiosis mutualisme dengan fungi ektomikoriza. Hal tersebut menjadikan pemulihan hutan tropis bergantung pada keberadaan fungi ektomikoriza. Peranan fungi ektomikoriza dalam mendukung regenerasi dijumpai dalam bentuk multi inang yang dapat terindikasi dari penggunaan secara bersama jenis fungi ektomikoriza antar tanaman. Berdasarkan hal tersebut, penelitian bertujuan untuk mengetahui jenis-jenis fungi ektomikoriza yang berasosiasi dengan dipterocarpaceae di tingkat pohon dan semai, serta mengetahui adanya multi inang fungi ektomikoriza pada kedua tingkat pertumbuhan tersebut. Penelitian ini dilakukan dengan mengidentifikasi ektomikoriza melalui pendekatan molekuler dengan menggunakan teknik Polymerase Chain Reaction (PCR). Urutan ekstrak DNA diperkuat menggunakan pasangan primer spesifik ITS 1F-ITS 4. Identitas fungi ektomikoriza diperoleh dari pencocokan urutan DNA sampel terhadap database Genbank. Berdasarkan hasil identifikasi, jenis-jenis fungi ektomikoriza yang berasosiasi dengan dipterocarpaceae di tingkat pohon dan semai mempunyai hubungan kekerabatan dengan kelas Dothideomycetesdan ordo Sordariales, Sebacinales, Cantharellales, Russulales, Agaricales, Boletales, dan Thelephorales. Penelitian juga menemukan multi inang fungi ektomikoriza terhadap dipterocarpaceae, baik pada jenis maupun tingkatan pertumbuhan inang yang berbeda (semai dan pohon). Jenis fungi ektomikoriza yang paling berperan dalam multi inang adalah fungi yang mempunyai hubungan kekerabatan dengan ordo Thelephorales, Russulales, dan Sebacinales.Tomentella sp. dari ordo Thelephorales ditemukan paling banyak berasosiasi multi inang pada pohon dan semai. R. lepidicolor, Sebacina sp., dan fungi ektomikoriza famili Thelephoraceae masing-masing berasosiasi multi inang di tingkat semai. Keberadaan jenis-jenis fungi ektomikoriza yang mampu berasosiasi secara multi inang dengan dipterocarpaceae merupakan modal alami upaya rehabilitasi hutan tropis terdegradasi. Multi-Host of Ectomycorrhizal Fungi on Dipterocarpaceae inTropical Rain ForestsAbstractDipterocarpaceae is known as the dominant forest vegetation family in tropical forests that has mutual symbiosis with ectomycorrhizal fungi. It makes tropical forest resilience depend on the existence of ectomycorrhizal fungi. The role of ectomycorrhizal fungi to support the regeneration was found in multi-host form, indicated by sharing ectomycorrhizal fungal species between plants. Based on that phenomenon, the study aims to recognize ectomycorrhizal fungi that associate with dipterocarpaceae at tree and seedling levels, and the presence of multi-host ectomycorrhizal fungi on both growth stages. The research was conducted by identifying the ectomycorrhizal fungi via molecular approach by using Polymerase Chain Reaction (PCR) technique. To strengthen the sequence of DNA extracts, a specific primer pair of ITS 1F-ITS 4 was used. The identity of the ectomycorrhizal fungi was obtained by matching the samples’DNA sequence to the Genbank database. Based on the identification results, ectomycorrhizal fungi that associate with dipterocarpaceae on tree and seedling levels have genetic relationship with Dothideomycetes class and Sordariales, Sebacinales, Cantharellales, Russulales, Agaricales, Boletales, and Thelephorales orders. The research also found that multi-host of ectomycorrhizal fungi to dipterocarpaceae is formed both in different species and growth stages of host (tree and seedling). The most ectomycorrhizal fungi that play a role in multi-host are those with genetic relationship to the orders of Thelephorales, Russulales, and Sebacinales. Tomentella sp. of Thelephorales order was the most multi-host on both tree and seedling levels. R. lepidicolor, Sebacina sp., and ectomycorrhizal fungi of Thelephoraceae were found multi-host in seedling level. The existence of ectomycorrhizal fungi associated in multi-host with dipterocarpaceae is a natural asset for rehabilitation effort of degraded tropical forests