Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016

Highly pathogenic avian influenza viruses (HPAIVs) A(H5N6) were concurrently introduced into several distant regions of Japan in November 2016. These viruses were classified into the genetic clade 2.3.4.4c and were genetically closely related to H5N6 HPAIVs recently isolated in South Korea and China. In addition, these HPAIVs showed further antigenic drift

Genome-wide SNP analysis reveals population structure and demographic history of the ryukyu islanders in the southern part of the Japanese archipelago.

The Ryukyu Islands are located to the southwest of the Japanese archipelago. Archaeological evidence has revealed the existence of prehistoric cultural differentiation between the northern Ryukyu islands of Amami and Okinawa, and the southern Ryukyu islands of Miyako and Yaeyama. To examine a genetic subdivision in the Ryukyu Islands, we conducted genome-wide single nucleotide polymorphism typing of inhabitants from the Okinawa Islands, the Miyako Islands, and the Yaeyama Islands. Principal component and cluster analyses revealed genetic differentiation among the island groups, especially between Okinawa and Miyako. No genetic affinity was observed between aboriginal Taiwanese and any of the Ryukyu populations. The genetic differentiation observed between the inhabitants of the Okinawa Islands and the Miyako Islands is likely to have arisen due to genetic drift rather than admixture with people from neighboring regions. Based on the observed genetic differences, the divergence time between the inhabitants of Okinawa and Miyako islands was dated to the Holocene. These findings suggest that the Pleistocene inhabitants, whose bones have been found on the southern Ryukyu Islands, did not make a major genetic contribution, if any, to the present-day inhabitants of the southern Ryukyu Islands

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells

Radiotherapy is effective for treating various types of tumors. However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes that correlate with poor prognosis. It is not known how cancer cells survive and generate malignant tumors after irradiation. Here, we show that activating transcription factor 5 (ATF5) promotes radioresistance and malignancy in cancer cells after irradiation. In the G1-S phase of the cell cycle, cancer cells express high levels of ATF5, which promotes cell cycle progression and thereby increases radioresistance. Furthermore, ATF5 increases malignant phenotypes, such as cell growth and invasiveness, in cancer cells in vitro and in vivo. We have identified a new mechanism for the regeneration of highly malignant tumors after irradiation and shown that ATF5 plays a key role in the process

Role of ATF5 in the invasive potential of diverse human cancer cell lines

Activating transcription factor 5 (ATF5) is a member of the ATF/CAMP response element-binding protein family. Our research group recently revealed that ATF5 expression increases the invasiveness of human lung carcinoma cells. However, the effects of ATF5 on the invasive potential of other cancer cells lines remain unclear. Therefore, in this study, we investigated the role of ATF5 in the invasive activity of diverse human cancer cell lines. Invasiveness was assessed using Matrigel invasion assays. ATF5 knockdown resulted in decreased invasiveness in seven of eight cancer cell lines tested. These results suggest that ATF5 promotes invasiveness in several cancer cell lines. Furthermore, the roles of ATF5 in the invasiveness were evaluated in three-dimensional (3D) culture conditions. In 3D collagen gel, HT-1080 and MDA-MB-231 cells exhibited high invasiveness, with spindle morphology and high invasion speed. In both cell lines, knockdown of ATF5 resulted in rounded morphology and decreased invasion speed. Next, we showed that ATF5 induced integrin-alpha 2 and integrin-beta 1 expression and that the depletion of integrin-alpha 2 or integrin-beta 1 resulted in round morphology and decreased invasion speed. Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-alpha 2 and integrin-beta 1 in several human cancer cell lines. (C) 2016 Elsevier Inc. All rights reserved

Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin β1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin β1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin β1-dependent phenotype, and integrin β1 might be a potentially effective therapeutic target in combination with radiotherapy

Irradiation-tolerant lung cancer cells acquire invasive ability dependent on dephosphorylation of the myosin regulatory light chain

Radiotherapy is one of the major treatment modalities for malignancies. However, cells surviving irradiation often display high levels of invasiveness. This study shows that irradiation-tolerant lung adenocarcinoma demonstrates high invasive capability depending on dephosphorylation of the myosin regulatory light chain (MRLC). In a collagen gel overlay condition, low-invasive subclones of lung adenocarcinoma (A549P-3) showed a round morphology and diphosphorylation of MRLC. In contrast, irradiation-tolerant A549P-3 cells (A549P-3IR) displayed high invasiveness and a lower level of MRLC diphosphorylation. In addition, inhibition of MRLC phosphatase activity decreased the invasive activity. These findings suggest that A549P-3IR cells acquire high invasiveness through MRLC dephosphorylation. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved

Osmotic gradients induce stable dome morphogenesis on extracellular matrix

One of the fundamental processes in morphogenesis is dome formation, but many of the mechanisms involved are unexplored. Previous in vitro studies showed that an osmotic gradient is the driving factor of dome formation. However, these investigations were performed without extracellular matrix (ECM), which provides structural support to morphogenesis. With the use of ECM, we observed that basal hypertonic stress induced stable domes in vitro that have not been seen in previous studies. These domes developed as a result of ECM swelling via aquaporin water transport activity. Based on computer simulation, uneven swelling, with a positive feedback between cell stretching and enhanced water transport, was a cause of dome formation. These results indicate that osmotic gradients induce dome morphogenesis via both enhanced water transport activity and subsequent ECM swelling

Effects of Field-Map Distortion Correction on Resting State Functional Connectivity MRI

Magnetic field inhomogeneities cause geometric distortions of echo planar images used for functional magnetic resonance imaging (fMRI). To reduce this problem, distortion correction (DC) with field map is widely used for both task and resting-state fMRI (rs-fMRI). Although DC with field map has been reported to improve the quality of task fMRI, little is known about its effects on rs-fMRI. Here, we tested the influence of field-map DC on rs-fMRI results using two rs-fMRI datasets derived from 40 healthy subjects: one with DC (DC+) and the other without correction (DC−). Independent component analysis followed by the dual regression approach was used for evaluation of resting-state functional connectivity networks (RSN). We also obtained the ratio of low-frequency to high-frequency signal power (0.01–0.1 Hz and above 0.1 Hz, respectively; LFHF ratio) to assess the quality of rs-fMRI signals. For comparison of RSN between DC+ and DC− datasets, the default mode network showed more robust functional connectivity in the DC+ dataset than the DC− dataset. Basal ganglia RSN showed some decreases in functional connectivity primarily in white matter, indicating imperfect registration/normalization without DC. Supplementary seed-based and simulation analyses supported the utility of DC. Furthermore, we found a higher LFHF ratio after field map correction in the anterior cingulate cortex, posterior cingulate cortex, ventral striatum, and cerebellum. In conclusion, field map DC improved detection of functional connectivity derived from low-frequency rs-fMRI signals. We encourage researchers to include a DC step in the preprocessing pipeline of rs-fMRI analysis