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Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques (Macaca fuscata) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-β/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating BATF3/IRF4 and MYC. In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-β/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-β/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.

Confining molecules in the nanoscale environment can lead to dramatic changes of their physical and chemical properties, which opens possibilities for new applications. There is a growing interest in liquefied gas electrolytes for electrochemical devices operating at low temperatures due to their low melting point. However, their high vapor pressure still poses potential safety concerns for practical usages. Herein, we report facile capillary condensation of gas electrolyte by strong confinement in sub-nanometer pores of metal-organic framework (MOF). By designing MOF-polymer membranes (MPMs) that present dense and continuous micropore (~0.8 nm) networks, we show significant uptake of hydrofluorocarbon molecules in MOF pores at pressure lower than the bulk counterpart. This unique property enables lithium/fluorinated graphite batteries with MPM-based electrolytes to deliver a significantly higher capacity than those with commercial separator membranes (~500 mAh g-1 vs.

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM) after a long latent period in a fraction of infected individuals. These HTLV-1-infected cells typically have phenotypes similar to that of CD4+T cells, but the cell status is not well understood. To extract the inherent information of HTLV-1-infected CD4+ cells, we integratively analyzed the ATAC-seq and RNA-seq data of the infected cells. Compared to CD4+T cells from healthy donors, we found anomalous chromatin accessibility in HTLV-1infected CD4+ cells derived from ATL cases in terms of location and sample-to-sample fluctuations in open chromatin regions. Further, by focusing on systematically selected genes near the open chromatin regions, we quantified the difference between the infected CD4+ cells in ATL cases and healthy CD4+T cells in terms of the correlation between the chromatin structures and the gene expressions. Based on a further analysis of chromatin accessibility, we detected TLL1 (Tolloid Like 1) as one of the key genes that exhibit unique gene expressions in ATL cases. A luciferase assay indicated that TLL1 has an isoform-dependent regulatory effect on TGF-β. Overall, this study provides results about the status of HTLV-1-infected cells, which are qualitatively consistent across the different scales of chromatin accessibility, transcription, and immunophenotype. Author summary: Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM) after a long latent period in a fraction of infected individuals. These HTLV-1-infected cells typically have phenotypes similar to that of CD4+T cells, but the cell status is not well understood. To extract the inherent information of HTLV-1-infected CD4+ cells, we integratively analyzed the ATAC-seq and RNA-seq data of the infected cells. Compared to CD4+T cells from healthy donors, we found anomalous properties in terms of chromatin accessibility and its relationship with the gene expressions in HTLV-1 infected CD4+ cells derived from ATL cases. Based on a further analysis of chromatin accessibility, we detected TLL1 (Tolloid Like 1) as one of the key genes that exhibit unique gene expressions in ATL cases. Indeed, our experiments indicated that TLL1 has an isoform-dependent regulatory effect on TGF-β. Overall, this study provides results about the status of HTLV-1-infected cells, which are qualitatively consistent across the different scales of chromatin accessibility, transcription, and immunophenotype. [ABSTRACT FROM AUTHOR]

Human T‐cell leukemia virus type 1 (HTLV‐1) establishes chronic infection in humans and induces a T‐cell malignancy called adult T‐cell leukemia‐lymphoma (ATL) and several inflammatory diseases such as HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV‐1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV‐1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV‐1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV‐1‐infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti‐Gag proteins to predict high risk group in HTLV‐1 carriers. Consistent with this finding, anti‐Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti‐Gag CTLs for disease control. Our findings suggest that our strategy that combines anti‐HTLV‐1 antibodies and proviral load may be useful for prediction of the development of HTLV‐1‐associated diseases. [ABSTRACT FROM AUTHOR]

Until a century ago, Korean medicine was based mainly on Oriental philosophies and ideas. From a religious perspective, Chinese Confucianism was prevalent in Korea at that time. Since Confucianists believe that it is against one's filial duty to harm his or her body, given to them by their parents, most Koreans did not donate their bodies or organs for education in the past. However, by the end of the 20th century, a unique fusion of Western and Oriental medicines were produced on the Korean Peninsula, revolutionizing traditional perspectives on the human body, mortality, and the relationship of medical science to society. Koreans began to think about others' lives as well as their own by realizing the importance of donating one's organs and bodies for scientific purposes. Since then, the number of people donating their bodies to Korean medical and dental schools for the purpose of improving academic learning has increased dramatically. In response, Korean medical schools have begun to hold various types of funeral ceremonies to honor body donors. We have compared such ceremonies performed in Korea with those performed in the United States of America and Taiwan. These ceremonies are viewed as a suitable way to pay proper respect to the dead and to promote knowledge about body donation programs in Korea. Overall, the transition of religions and social ethics in Korea has greatly facilitated body bequeathal programs, benefiting both medical education and the Korean public health administration. (Contains 4 figures.)