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

Indian Monsoonal Variations During the Past 80 Kyr Recorded in NGHP-02 Hole 19B, Western Bay of Bengal: Implications From Chemical and Mineral Properties

金沢大学理工研究域地球社会基盤学系Detailed reconstruction of Indian summer monsoons is necessary to better understand the late Quaternary climate history of the Bay of Bengal and Indian peninsula. We established a chronostratigraphy for a sediment core from Hole 19B in the western Bay of Bengal, extending to approximately 80 kyr BP and examined major and trace element compositions and clay mineral components of the sediments. Higher δ 18 O values, lower TiO 2 contents, and weaker weathering in the sediment source area during marine isotope stages (MIS) 2 and 4 compared to MIS 1, 3, and 5 are explained by increased Indian summer monsoonal precipitation and river discharge around the western Bay of Bengal. Clay mineral and chemical components indicate a felsic sediment source, suggesting the Precambrian gneissic complex of the eastern Indian peninsula as the dominant sediment source at this site since 80 kyr. Trace element ratios (Cr/Th, Th/Sc, Th/Co, La/Cr, and Eu/Eu*) indicate increased sediment contributions from mafic rocks during MIS 2 and 4. We interpret these results as reflecting the changing influences of the eastern and western branches of the Indian summer monsoon and a greater decrease in rainfall in the eastern and northeastern parts of the Indian peninsula than in the western part during MIS 2 and 4. © 2018. American Geophysical Union. All Rights Reserved

Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia

Abstract Background Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer’s disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells. Methods We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization using fura-2 imaging and tested the effects of donepezil on phagocytic activity by phagocytosis assay in rodent microglial cells. Results In this study, we observed that pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation in both rat HAPI and mouse primary microglial cells. On the other hand, pretreatment with donepezil did not suppress the mRNA expression of both TNFR1 and TNFR2 in rodent microglia we used. Pretreatment with acetylcholine but not donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the nicotinic α7 receptors. In addition, sigma 1 receptors were not involved in the donepezil-induced suppression of the TNFα-mediated intracellular Ca2+ elevation. Pretreatment with donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the PI3K pathway in rodent microglial cells. Using DAF-2 imaging, we also found that pretreatment with donepezil suppressed the production of NO induced by TNFα treatment and the PI3K pathway could be important for the donepezil-induced suppression of NO production in rodent microglial cells. Finally, phagocytosis assay showed that pretreatment with donepezil promoted phagocytic activity of rodent microglial cells through the PI3K but not MAPK/ERK pathway. Conclusions These suggest that donepezil could directly modulate the microglial function through the PI3K pathway in the rodent brain, which might be important to understand the effect of donepezil in the brain

Additional file 3: Figure S3. of Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia

Sigma 1 receptors were not involved in the donepezil-induced suppression of the TNFα-mediated intracellular Ca2+ elevation in rodent microglial cells. Pretreatment with 5 μM donepezil and 10 μM BD1047, an antagonist of sigma-1 receptors, for 12 h significantly inhibited the elevation of [Ca2+]i induced by TNFα in rat HAPI microglial cells. In this panel, the average trace determined from 5 representative traces of [Ca2+]i in each condition. Dotted line is the average trace of control. (TIFF 222 kb

Additional file 1: Figure S1. of Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia

Five representative traces showing that donepezil alone did not affect [Ca2+]i in mouse primary microglial cells. (TIFF 901 kb

Additional file 2: Figure S2. of Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia

Five representative traces showing that donepezil applied after the onset of TNFÎą-induced intracellular Ca2+ elevation did not affect [Ca2+]i in mouse primary microglial cells (TIFF 923 kb

Development and external validation of a deep learning-based computed tomography classification system for COVID-19

[BACKGROUND] We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). [METHODS] We used 2, 928 images from a wide variety of case-control type data sources for the development and internal validation of the machine learning model. A total of 633 COVID-19 cases and 2, 295 non-COVID-19 cases were included in the study. We randomly divided cases into training and tuning sets at a ratio of 8:2. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR. [RESULTS] In external validation, the sensitivity and specificity of the model were 0.869 and 0.432, at the low-level cutoff, 0.724 and 0.721, at the high-level cutoff. Area under the receiver operating characteristic was 0.76. [CONCLUSIONS] Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner at emergency departments. Further studies are warranted to improve model specificity