Simultaneous siRNA Targeting of Src and Downstream Signaling Molecules Inhibit Tumor Formation and Metastasis of a Human Model Breast Cancer Cell Line

Src and signaling molecules downstream of Src, including signal transducer and activator of transcription 3 (Stat3) and cMyc, have been implicated in the development, maintenance and/or progression of several types of human cancers, including breast cancer. Here we report the ability of siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc to inhibit the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S, a widely used model for breast cancer research.Src and its downstream signaling partners were specifically targeted and knocked-down using siRNA. Changes in the growth properties of the cultured cancer cells/tumors were documented using assays that included anchorage-dependent and -independent (in soft agar) cell growth, apoptosis, and both primary and metastatic tumor growth in the mouse tumor model. siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc inhibited the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S. This knock-down resulted in reduced growth in monolayer and soft agar cultures, and a reduced ability to form primary tumors in NOD/SCID mice. In addition, direct intra-tumoral injection of siRNAs targeting these signaling molecules resulted in a substantial inhibition of tumor metastases as well as of primary tumor growth. Simultaneous knock-down of Src and Stat3, and/or Myc exhibited the greatest effects resulting in substantial inhibition of primary tumor growth and metastasis.These findings demonstrate the effectiveness of simultaneous targeting of Src and the downstream signaling partners Stat3 and/or cMyc to inhibit the growth and oncogenic properties of a human cancer cell line. This knowledge may be very useful in the development of future therapeutic approaches involving targeting of specific genes products involved in tumor growth and metastasis

Climatic risks and impacts in South Asia: extremes of water scarcity and excess

This paper reviews the current knowledge of climatic risks and impacts in South Asia associated with anthropogenic warming levels of 1.5°C to 4°C above pre-industrial values in the 21st century. It is based on the World Bank Report “Turn Down the Heat, Climate Extremes, Regional Impacts and the Case for Resilience” (2013). Many of the climate change impacts in the region, which appear quite severe even with relatively modest warming of 1.5–2°C, pose significant hazards to development. For example, increased monsoon variability and loss or glacial meltwater will likely confront populations with ongoing and multiple challenges. The result is a significant risk to stable and reliable water resources for the region, with increases in peak flows potentially causing floods and dry season flow reductions threatening agriculture. Irrespective of the anticipated economic development and growth, climate projections indicate that large parts of South Asia’s growing population and especially the poor are likely to remain highly vulnerable to climate change

Tracking students’ visual attention on manga-based interactive e-book while reading: an eye-movement approach

[[abstract]]This study employed an eye tracking technology to explore university students’ visual attention and learning performance while learning Japanese using an interactive manga-based e-book. The developed e-book consisted of 8 pages accompanied by 13 annotations with both text and graphical formats. The subjects consisted of 60 students whose eye movements were tracked and recorded by the eye tracking system. These students came from the applied foreign language department in a northern university in Taiwan, of which 30 were assigned to high prior knowledge (PK) group and the other 30 were assigned to low PK group. Eye tracking measurements, including total contact time, number of fixations, latency of first fixation, and number of clicks on the defined regions of interest of the two groups were compared to indicate their visual attention. The results revealed that overall students spent more time on reading text and annotation than graphic information. The high PK students showed longer fixation durations on the texts, while the low PK students showed longer fixation durations on the graphics and annotations. Meanwhile, the low PK students used more clicks to look up underlined annotations whenever they didn’t know words or phrases on the e-book. In addition, with respect to the latency of the first fixation, the graphic captured the attention faster than the text because of the size and its appeal to the students. Further analysis of saccade paths indicated that the low PK students showed more inter-scanning transitions not only between the text dialog and the annotation zone but also within annotation zone. Finally, the results of reading comprehension pretest and posttest found that there was a significant difference in learning outcomes between each PK group.[[notice]]補正完