ONLINE MEASUREMENT OF VOCS EMISSIONS FROM VEHICLES USING A PORTABLE SAMPLING SYSTEM

Joint Research on Environmental Science and Technology for the Eart

Paradoxical activation of c-Src as a drug-resistant mechanism

抗がん剤抵抗性の新規メカニズムの解明 --薬剤抵抗性がん細胞は抗がん剤により増殖する--. 京都大学プレスリリース. 2021-03-25.ATP-competitive inhibitors have been developed as promising anti-cancer agents. However, drug-resistance frequently occurs, and the underlying mechanisms are not fully understood. Here, we show that the activation of c-Src and its downstream phosphorylation cascade can be paradoxically induced by Src-targeted and RTK-targeted kinase inhibitors. We reveal that inhibitor binding induces a conformational change in c-Src, leading to the association of the active form c-Src with focal adhesion kinase (FAK). Reduction of the inhibitor concentration results in the dissociation of inhibitors from the c-Src-FAK complex, which allows c-Src to phosphorylate FAK and initiate FAK-Grb2-mediated Erk signaling. Furthermore, a drug-resistant mutation in c-Src, which reduces the affinity of inhibitors for c-Src, converts Src inhibitors into facilitators of cell proliferation by enhancing the phosphorylation of FAK and Erk in c-Src-mutated cells. Our data thus reveal paradoxical enhancement of cell growth evoked by target-based kinase inhibitors, providing potentially important clues for the future development of effective and safe cancer treatment

Factors Determining Satisfaction with Daily Life of Elderly A-bomb Survivors

From the analysis of questionnaires to elderly A-bomb survivors of over 65 years old, we analysed factors which determined satisfaction with daily life. Analysed categories were housing condition, life style, occupational status, health condition and family status. From the analysis, to be an A-bomb survivor was not a factor for satisfaction with daily life, and it became clear that living in a rented room, not satisfying one\u27s job and low income were serious factors which kept elderly people from the satisfaction with daily life. It must be necessary to improve these factors for the satisfaction of elderly people

PITHD1 is essential for male fertilization

The proteasome is a protein-degrading molecular complex that is necessary for protein homeostasis and various biological functions, including cell cycle regulation, signal transduction, and immune response. Proteasome activity is finely regulated by a variety of proteasome-interacting molecules. PITHD1 is a recently described molecule that has a domain putatively capable of interacting with the proteasome. However, it is unknown as to whether PITHD1 can actually bind to proteasomes and what it does in vivo. Here we report that PITHD1 is detected specifically in the spermatids in the testis and the cortical thymic epithelium in the thymus. Interestingly, PITHD1 associates with immunoproteasomes in the testis, but not with thymoproteasomes in the thymus. Mice deficient in PITHD1 exhibit severe male infertility accompanied with morphological abnormalities and impaired motility of spermatozoa. Furthermore, PITHD1 deficiency reduces proteasome activity in the testis and alters the amount of proteins that are important for fertilization capability by the sperm. However, the PITHD1-deficient mice demonstrate no detectable defects in the thymus, including T cell development. Collectively, our results identify PITHD1 as a proteasome-interacting protein that plays a nonredundant role in the male reproductive system

PITHD1 is a proteasome-interacting protein essential for male fertilization

Hiroyuki Kondo, Takafumi Matsumura, Mari Kaneko, Kenichi Inoue, Hidetaka Kosako, Masahito Ikawa, Yousuke Takahama, Izumi Ohigashi, PITHD1 is a proteasome-interacting protein essential for male fertilization, Journal of Biological Chemistry, Volume 295, Issue 6, 2020, Pages 1658-1672, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA119.011144

The role of a group III AQP, AQP11 in intracellular organelle homeostasis

AQP11 is a member of a new aquaporin subfamily which includes many aquaporin homologs with low amino acid identities, around 20% of previously identified AQPs. Although these AQPs have unusual NPA sequences, these AQPs have a completely conserved and functionally indispensable cysteine residue downstream of the second NPA box, suggesting that they belong to a specific AQP subfamily, which we propose to name the group III AQPs. On the other hand, the NPA boxes are highly conserved in previous AQP subfamilies : the group I AQPs, original water-selective aquaporin family and the group II AQPs, aquaglyceroporin family. Currently the roles of the group III AQPs are only known with AQP11 as the disruption of intracellularly located AQP11 in mice produced huge vacuoles in the proximal tubule leading to fatal polycystic kidneys at one month old. This review focused on the classification of AQPs based on primary structures to obtain insights into the function and the role of AQPs. With the accumulation of new AQP-like sequences through genome projects, this classification will be useful to predict their functions as each group may have specific characteristics in its function, distribution and regulation