Post-translational modifications of the apelin receptor regulate its functional expression

Post-translational modifications (PTMs) are protein modifications that occur after protein biosynthesis, playing a crucial role in regulating protein function. They are involved in the functional expression of G-protein-coupled receptors (GPCRs), as well as intracellular and secretory protein signaling. Here, we aimed to investigate the PTMs of the apelin receptor (APLNR), a GPCR and their potential influence on the receptor's function. In an in vitro experiment using HEK cells, we only observed glycosylation as a PTM of the APLNR and ineffective receptor signaling by the agonist, (Pyr1)-apelin-13. In contrast, when analyzing mouse spinal cord, we detected glycosylation and other PTMs, excluding isopeptidation. This suggests that additional PTMs are involved in the functional expression of the APLNR in vitro. In summary, these findings suggest that the APLNR in vivo requires multiple PTMs for functional expression. To comprehensively understand the pharmacological effects of the APLNR, it is essential to establish an in vitro system that adequately replicates the receptor's PTM profile. Nonetheless, it is crucial to overcome the challenge of heat-sensitive proteolysis in APLNR studies. By elucidating the regulation of PTMs, further research has the potential to advance the analysis and pharmacological studies of both the apelin/APLNR system and GPCR signal modulation

環境デザインの国際ワークショップ開催に向けた坂出市に関する基礎調査

本研究では、近年中の実施を予定している環境デザインの国際ワークショップの準備を兼ねて、その開催候補地である坂出市の将来構想の策定とまちづくり戦略の立案に役立てるための基礎調査を行う。　古くから瀬戸内海の海上交通の要所として、また、瀬戸大橋開通後は、陸上交通における四国の玄関口として発展してきた坂出市であるが、人口減少時代を迎えて社会構造と産業構造が大きく転換しつつある今、市内では様々な問題が各所で顕在化している。その一方、島嶼部や山域部の美しい自然、平野部に広がる農地、市街地内の歴史文化資源等については、それらの価値や潜在力が、これまで十分に活用されてきたとは言い難い。　今回の調査においては、最初に地域の特色を広域的な観点から把握し、地勢的な特質から坂出市域を4つのゾーン（抱護ゾーン、中核ゾーン、臨海ゾーン、島嶼ゾーン）に区分した。その上で、現地調査および関係者へのヒアリングを通して、ゾーンごとの様々な課題ならびに多様な地域資源の分布に関する把握整理を行った。　結果として、場所ごとの多くの課題と今後の利活用がのぞまれる豊富な地域資源の存在が明らかになった。今後、新しい時代の戦略的なまちづくりの方策づくりに向けて、これらの成果を生かしていきたい。This research aims to acquire and sort out basic information about the city of Sakaide, as a preparatory work for an international workshop of environmental design which is to be held in the following years. The city of Sakaide has been developed since ancient times as a strategic place of sea traffic being located at the middle of Seto Inland Sea. The importance of the city further augmented when the construction of the Seto Ohashi Bridge was completed in 1988. However, now in the age of depopulation, with the drastic change of social and industrial conditions, many problems have emerged in different areas in the city. In this research, the city area is divided into four zones according to the geographical features, namely enclosure zone, central zone, waterfront zone, and island zone. Various problems and local resources are recognized through field survey and interviews. The result of this research will be applied not only to the following workshop but also to draw up a strategic city vision of Sakaide in the new age

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes?:Systematic review

background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. methods: Systematic review of the literature and narrative synthesis. results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers