Vorinostat approved in Japan for treatment of cutaneous T-cell lymphomas: status and prospects

Histone acetylation and deacetylation play important roles in the regulation of gene transcription and in the modulation of chromatin structure. The levels of histone acetylation are determined by the activities of histone acetyltransferases and histone deacetylases (HDACs). HDACs are associated with a number of oncogenes and tumor suppressor genes and can be aberrantly expressed and/or inappropriately activated in cancer cells. HDAC inhibitors have therefore recently emerged as a novel treatment modality against malignancies. They regulate gene expression by enhancing the acetylation of not only histones but also nonhistone proteins, including transcription factors, transcription regulators, signal transduction mediators, and DNA repair enzymes, and they inhibit cancer growth. Vorinostat (suberoylanilide hydroxamic acid) is one of the most potent HDAC inhibitors, and was approved in Japan in 2011 for the treatment of cutaneous T-cell lymphoma. Numerous clinical trials have shown it to be effective against cutaneous T-cell lymphoma but less so against other types of cancer. Because vorinostat can overcome resistance to or enhance the efficacy of other anticancer agents, such as 5-fluorouracil, carboplatin, paclitaxel, bortezomib, and tamoxifen, combination therapies using vorinostat and these agents have been investigated. This review introduces the background and mechanism of action of vorinostat and describes the results of clinical trials using vorinostat, both as a single agent and in combination with other anticancer agents, against cutaneous T-cell lymphoma and other malignancies

DETERMINATION OF THE OPTIMAL NUMBER OF RIGID-BODY SEGMENTS TO REPRESENT THE TRUNK USING AKAIKE’S INFORMATION CRITERION

The purpose of this study was to determine the optimal number of rigid body segments to sufficiently represent the trunk movements, using Akaike’s information criterion. The trunk in static and dynamic conditions was modelled with one, two, three, or six linked rigid-body representations. The difference in the three-dimensional position between the actual and modelled data was calculated to quantify how well these models describe the actual trunk kinematics. The Akaike’s information criterion was calculated using the difference in position data to evaluate the goodness-of-fit for each model. Our findings suggest that two-linked rigid-body representation may be good enough when analysing trunk movements except when the movement includes a large axial rotation, for which the three-linked rigid-bodies would be better. These results would be useful in determining the optimal number of rigid body representation to sufficiently represent the trunk movements

Scaling of soaring seabirds and its implication for the maximum size of flying pterosaurs

The flight ability of animals is restricted by the scaling effects imposed by physical and physiological factors. In comparisons of the power available from muscle and the mechanical power required to fly, theoretical studies have predicted that the margin between the powers should decrease with body size and that flying animals have a maximum body size. However, predicting an absolute value of this upper limit has been difficult because wing morphology and flight styles vary among species. Albatrosses and petrels have long, narrow, aerodynamically efficient wings and are considered to be soaring birds. Here, using animal-borne accelerometers, we show that scaling analyses of wing-flapping frequencies in these seabirds indicate that the maximum size limit for soaring animals is a body mass of 41 kg and a wingspan of 5.1 m. Soaring seabirds were observed to have two modes of flapping frequencies: vigorous flapping during takeoff and sporadic flapping during cruising flight. In these species, high and low flapping frequencies were found to scale with body mass (_mass_ ^-0.30^ and _mass_ ^-0.18^) in a manner similar to the predictions from biomechanical flight models (_mass_ ^-1/3^ and _mass_ ^-1/6^). The scaling relationships predicted that animals larger than the limit will not be able to flap fast enough to stay aloft under unfavourable wind conditions. Our result therefore casts doubt on the flying ability of large, extinct pterosaurs. The largest extant soarer, the wandering albatross, weighs about 10 kg, which might be a pragmatic limit to maintain a safety margin for sustainable flight and to survive in a variable environment

IDE Gene Polymorphism Influences on BPSD in Mild Dementia of Alzheimer's Type

Insulin degrading enzyme (IDE) degrades amyloid β (Aβ), which may inhibit the accumulation of Aβ in a brain affected with dementia of Alzheimer's type (DAT). A decrease in the activity of IDE results in changes in glucose utilization in the brain, which could affect the cognitive and psychiatric symptoms of DAT. We investigated a possible association of IDE gene polymorphism and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for IDE and apolipoprotein E (ApoE) was determined in 207 patients with mild DAT and 215 controls. The occurrence of BPSD was demonstrated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). IDE gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of affective disturbance through the course of mild DAT, regardless of the presence of an ApoE ε4 allele. The present data could be the result of a small sample size. Further investigations using larger samples are thus required to clarify the correlation between IDE gene polymorphism, susceptibility to DAT, and emergence of BPSD

Two new species of Exobasidium causing Exobasidium diseases on Vaccinium spp. in Japan

Abstract Two new Exobasidium species on Vaccinium spp. in Japan are described and discussed. Exobasidium kishianum, which causes Exobasidium leaf blight on I/. hirtum var. pubescens and V. smallii, is characterized by its ellipsoid to ovoid basidiospores with (0-)1-3 septa. Its systemic infection is also observed. Exobasidium inconspicuum, cansing Exobasidium leaf blister on V. hirtum vat. pubescens, is characterized by its obovoid or ellipsoid to oval basidiospores with 0-4 septa. Mode of germination of the basidiospores is by germ tube in both species

Current status and future plan of the Program of the Antarctic Syowa MST/IS radar (PANSY)

The Tenth Symposium on Polar Science/Special session: [S] Future plan of Antarctic research: Towards phase X of the Japanese Antarctic Research Project (2022-2028) and beyond, Tue. 3 Dec. / 2F Auditorium, National Institute of Polar Researc

Crepuscular foraging by king penguins : behavioral adjustment to the diel vertical migration of prey

The Tenth Symposium on Polar Science/Ordinary sessions : [OB] Polar Biology, Wed. 4 Dec. / Entrance Hall (1st floor) , National Institute of Polar Researc