The spatio-temporal structure of the Lateglacial to early Holocene transition reconstructed from the pollen record of Lake Suigetsu and its precise correlation with other key global archives:Implications for palaeoclimatology and archaeology

Leads, lags, or synchronies in climatic events among different regions are key to understanding mechanisms of climate change, as they provide insights into the causal linkages among components of the climate system. The well-studied transition from the Lateglacial to early Holocene (ca. 16–10 ka) contains several abrupt climatic shifts, making this period ideal for assessing the spatio-temporal structure of climate change. However, comparisons of timings of past climatic events among regions often remain hypothetical because site-specific age scales are not necessarily synchronised to each other. Here we present new pollen data (n = 510) and mean annual temperature reconstruction from the annually laminated sediments of Lake Suigetsu, Japan. Suigetsu's 14C dataset is an integral component of the IntCal20 radiocarbon calibration model, in which the absolute age scale is established to the highest standard. Its exceptionally high-precision chronology, along with recent advances in cosmogenic isotope studies of ice cores, enables temporally coherent comparisons among Suigetsu, Greenland, and other key proxy records across regions. We show that the onsets of the Lateglacial cold reversal (equivalent to GS-1/Younger Dryas) and the Holocene were synchronous between East Asia and the North Atlantic, whereas the Lateglacial interstadial (equivalent to GI-1/Bølling-Allerød) started ca. two centuries earlier in East Asia than in the North Atlantic. Bimodal migration (or ‘jump’) of the westerly jet between north and south of the Tibetan plateau and Himalayas may have operated as a threshold system responsible for the abruptness of the change in East and South (and possibly also West) Asia. That threshold in Asia and another major threshold in the North Atlantic, associated with switching on/off of the Atlantic meridional overturning circulation (AMOC), were crossed at different times, producing a multi-centennial asynchrony of abrupt changes, as well as a disparity of climatic modes among regions during the transitional phases. Such disparity may have disturbed zonal circulation and generated unstable climate during transitions. The intervening periods with stable climate, on the other hand, coincided with the beginnings of sedentary life and agriculture, implying that these new lifestyles and technologies were not rational unless climate was stable and thus, to a certain extent, predictable

Structural basis of cytokine-mediated activation of ALK family receptors

Anaplastic lymphoma kinase (ALK)(1) and the related leukocyte tyrosine kinase (LTK)(2) are recently deorphanized receptor tyrosine kinases(3). Together with their activating cytokines, ALKAL1 and ALKAL2(4-6) (also called FAM150A and FAM150B or AUG beta and AUG alpha, respectively), they are involved in neural development(7), cancer(7-9) and autoimmune diseases(10). Furthermore, mammalian ALK recently emerged as a key regulator of energy expenditure and weight gain(11), consistent with a metabolic role for Drosophila ALK(12). Despite such functional pleiotropy and growing therapeutic relevance(13,14), structural insights into ALK and LTK and their complexes with cognate cytokines have remained scarce. Here we show that the cytokine-binding segments of human ALK and LTK comprise a novel architectural chimera of a permuted TNF-like module that braces a glycine-rich subdomain featuring a hexagonal lattice of long polyglycine type II helices. The cognate cytokines ALKAL1 and ALKAL2 are monomeric three-helix bundles, yet their binding to ALK and LTK elicits similar dimeric assemblies with two-fold symmetry, that tent a single cytokine molecule proximal to the cell membrane. We show that the membrane-proximal EGF-like domain dictates the apparent cytokine preference of ALK. Assisted by these diverse structure-function findings, we propose a structural and mechanistic blueprint for complexes of ALK family receptors, and thereby extend the repertoire of ligand-mediated dimerization mechanisms adopted by receptor tyrosine kinases

Safety and efficacy of high-dose cytarabine MEAM therapy and other treatments for auto-peripheral blood stem cell transplantation: A retrospective comparative study

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小規模・高齢化集落(限界集落)をめぐる問題を「解消する」

はじめに / 第1章 シンポジウムに対する疑問と提案 / 第2章 家族と地域社会から見た「限界集落」 / 第3章 研究者の「限界集落」に対するまなざし / 第4章 「問題解消型」の学問の役割と「問題解決型」の学問との連携 / おわり