Search

Background: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders. Methods: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines. Results: AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P

A 37‐year‐old woman developed persistent low‐grade fever (37.2°C) on day +13 after the first dose of BNT162b2 mRNA vaccine. She noticed coin‐sized hair loss on day +22, and it became widespread within 1 week. The patient's hair mostly recovered leaving only one oval bald patch on day +310 with topical corticosteroid therapy alone.

We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing. The control and management of the Loss in Weight (LIW) feeder were deemed the most important, and the Residence Time Distribution (RTD) model were regarded effective for setting the control range and for controlling of the LIW feeder. Based on these ideas, the concept of process control using RTD was summarized. The presented contents can serve as a solid fundament for adopting a new control method of continuous direct compression processes in and beyond the Japanese market.

Abstract Band‐shaped presentation of cutaneous angiosarcoma has not been reported. Cutaneous angiosarcoma should be included in the differential diagnosis when a persistent erythematous lesion is observed in the head and neck region of an elderly patient without a clear explanation, but skin biopsy is required for an accurate diagnosis.

This paper presents the stable isotope data of the snow pack and summer precipitation collected at the July 1 Glacier, Qilian Mountains in northwest China and analyses their relationships with meteorological factors. On an event scale, there is no temperature effect on the δ18O values in the summer precipitation, whereas the amount effect is shown to be clear. By tracing the moisture transport history and comparing the precipitation with its isotopic composition, it is shown that this amount effect not only reflects the change in moisture trajectory, which is related to the monsoon activities, but is also associated with the cooling degree of vapor in the cloud, the evaporation of falling raindrops and the isotopic exchange between the falling drops and the atmospheric vapor. As very little precipitation occurs in winter, the snow pack profile mainly represents the precipitation in the other three seasons. There are low precipitation δ18O ratios in summer and high ratios in spring and autumn. The Meteoric Water Line (MLW) for the summer precipitation is δD = 7.6 δ18O + 13.3, which is similar to that at Delingha, located in the south rim of the Qilian Mountains. The MWL for the snow pack is δD = 10.4 δ18O + 41.4, showing a large slope and intercept. The deuterium excess (d) of the snow pack is positively correlated with δ18O, indicating that both d and δ18O decrease from spring to summer and increase from early autumn to early spring. This then results in the high slope and intercept of the MWL. Seasonal fluctuations of d in the snow pack indicate the change of moisture source and trajectory. During spring and autumn, the moisture originates from continental recycling or rapid evaporation over relatively warm water bodies like Black, Caspian and Aral Seas when the dry westerly air masses pass over them, hence very high d values in precipitation are formed. During summer, the monsoon is responsible for the low d values. This indicates that the monsoon can reach the western part of the Qilian Mountains. [ABSTRACT FROM AUTHOR]

The importance of voltage-dependent Ca2+ channels (VDCCs) in pain transmission has been noticed gradually, as several VDCC blockers have been shown to be effective in inhibiting this process. In particular, the N-type VDCC has attracted attention, because inhibitors of this channel are effective in various aspects of pain-related phenomena. To understand the genuine contribution of the N-type VDCC to the pain transmission system, we generated mice deficient in this channel by gene targeting. We report here that mice lacking N-type VDCCs show suppressed responses to a painful stimulus that induces inflammation and show markedly reduced symptoms of neuropathic pain, which is caused by nerve injury and is known to be difficult to treat by currently available therapeutic methods. This finding clearly demonstrates that the N-type VDCC is essential for development of neuropathic pain and, therefore, controlling the activity of this channel can be of great importance for the management of neuropathic pain. [ABSTRACT FROM AUTHOR]

Positive degree-day factors for ice ablation on Yala Glacier, central Nepal, Xiao. . . [ABSTRACT FROM AUTHOR]

The timely breakdown of the extracellular matrix by proteolytic enzymes is essential for development, morphogenesis and cell proliferation in plant and animal cells. Sporangin of the unicellular green alga Chlamydomonas reinhardtii that mediates breakdown of the sporangial cell wall to liberate the daughter cells after cell division is characterized as a subtilase-like serine protease. The sporangin gene is specifically transcribed during S/M phase in a synchronized vegetative cell cycle. In immunoblot analyses using a polyclonal antibody raised against the sporangin polypeptide, the enzyme is synthesized after mitotic cell division and accumulated in the daughter cells before hatching. Immunofluorescence analyses showed that sporangin is localized to the flagella of the daughter cells within the sporangial cell wall, and released into the culture medium. The data suggest that sporangin is released from flagella concurrently with the digestion of sporangial cell wall, and then the daughter cells are hatched from the sporangia in the Chlamydomonas vegetative cell cycle. [ABSTRACT FROM AUTHOR]

When mating type plus and minus gametes of Chlamydomonas are mixed, they agglutinate with each other via their flagella, fuse, then initiate the zygote formation program which includes synthesis of the zygote cell wall, fusion of nuclei and chloroplasts, and the digestion of chloroplast DNA from the minus parent. The mRNAs from gamete and zygote cells was isolated and hybridized to cDNA-macroarray filters both to identify new genes expressed during the mating reaction and the early zygote formation process and to analyze the gene expression programs that underlie these sexual processes. Twenty-one novel genes were identified in this screen, designated as EZY (early zygote expressed) genes. The EZY genes included genes encoding proteins whose function is unknown, and genes encoding proteins that appear to be involved in processes such as cell wall synthesis, gene expression, intracellular trafficking or secretion, and vesicular transport in zygotic cells. All of the EZY genes were strongly induced within 1 h during the mating process, including early zygote formation. The transcriptional characteristics of EZY genes were analyzed by using the fusion-defective mutant fus mt+. Among the EZY genes, 12 genes were not activated in fusion-defective conditions, suggesting that cell fusion is required for their expression. The remaining nine that were transcribed in fusion-defective fus matings were also inducible by cell wall removal in either vegetative or gametic cells, indicating that these genes were induced only indirectly by the cAMP signaling pathway initiated by flagellar agglutination as a result of mating-induced cell wall loss. [ABSTRACT FROM AUTHOR]