Construction of a 'global standardised growth curve' (gSGC) for infrared Construction of a 'global standardised growth curve' (gSGC) for infrared stimulated luminescence dating of K-feldspar stimulated luminescence dating of K-feldspar

The Nihewan Basin is a key region for studying the Palaeolithic archaeology of East Asia. However, because of the lack of suitable dating methods and representative lithic technologies in this region, the 'Middle Palaeolithic' sites in this basin have been designated based mainly on stratigraphic correlation, which may be unreliable. In this study, three Palaeolithic sites, Motianling, Queergou and Banjingzi, which have been assigned previously to the 'Middle Palaeolithic', are dated based on luminescence dating of K-feldspar grains. Our results show that the cultural layers at Motianling, Queergou and Banjingzi have ages of 315 ± 13, 268 ± 13 and 86 ± 4 ka (corresponding to Marine Isotope Stages 9, 8 and 5), respectively, suggesting that Motianling and Queergou should be assigned to the Lower Palaeolithic, while the age of Banjingzi is consistent with a Middle Palaeolithic attribution. Our results suggest that reassessing the age of 'Middle Palaeolithic' sites in the Nihewan Basin, and elsewhere in North China, is crucial for understanding the presence or absence of the Middle Palaeolithic phase in China. Our dating results also indicate that the Sanggan River developed sometime between about 270 and 86 ka ago. Disciplines Medicine and Health Sciences | Social and Behavioral Sciences AbstractThe Nihewan Basin is a key region for studying the Palaeolithic archaeology of East Asia. However,

BackgroundA new subset of T helper (Th) cells, named IL-22-producing Th22 cells, was identified recently. Th22 cells have been implicated in immunity and inflammation. However, the role of these cells in the progression from acute viral myocarditis (AVMC) to dilated cardiomyopathy (DCM) and myocardial fibrosis remains unknown.MethodsBALB/c mice were repeatedly i.p. infected with Coxsackie virus B3 (CVB3) to establish models of AVMC, chronic myocarditis and DCM. On week 2, 12 and 24 post initial injection, the percentage of splenic Th22 cells, the levels of plasma IL-22, cardiac IL-22 receptor (IL-22R) expression, and indicators of myocardial fibrosis were measured. Further, mice with AVMC and chronic myocarditis were treated with an anti-IL-22 neutralizing antibody (Ab). The collagen volume fraction (CVF), the percentage of splenic Th22 cells, plasma IL-22 levels, cardiac IL-22R expression and indicators of myocardial fibrosis were then monitored.ResultsCompared to control mice at the same time points, AVMC, chronic myocarditis and DCM mice have higher percentage of splenic Th22 cells, higher plasma IL-22 levels, increased cardiac IL-22R, as well as increased collagen typeI-A1 (COL1-A1), collagen type III-A1 (COL3-A1) and matrix metalloproteinase-9 (MMP9) expression. However, the expression of tissue inhibitor of metalloproteinase-1(TIMP-1) was decreased. Treatment of AVMC and chronic myocarditis mice with an anti-IL-22 Ab decreased the survival rate and exacerbated myocardial fibrosis. The percentage of splenic Th22 cells, plasma IL-22 levels and cardiac IL-22R expression also decreased in anti-IL-22 Ab treatment group as compared to IgG and PBS treated groups of AVMC and chronic myocarditis mice. Moreover, increased expression of COL1-A1, COL3-A1, MMP9 but decreased expression of TIMP-1 were observed in anti-IL-22 Ab mouse group.ConclusionsTh22 cells play an important role in the pathogenesis of CVB3-induced mouse chronic myocarditis and DCM. IL-22 is a myocardium-protective cytokine by inhibiting myocardial fibrosis. Therefore, Th 22 cells may be considered as potential therapeutic targets for DCM.

Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC–MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V-infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

It has been suggested that the ‘small‐tool’ and microblade Upper Palaeolithic industries coexisted in the Nihewan Basin of northern China for about 8–14 000 years during Marine Isotope Stage (MIS) 2. This inference was based on uranium‐series ages of around 15 and 18 ka for bovid teeth recovered from the ‘latest’ small‐tool site of Xibaimaying – the youngest occurrence of such tools in the region – and optically stimulated luminescence (OSL) dating of the earliest typical microblade site (Youfang: ∼26–29 ka). In this study, we re‐dated the Xibaimaying site using single‐grain OSL methods and the resulting ages indicate that the cultural layer was deposited 46 ± 3 ka ago, during MIS 3 – more than 20 millennia earlier than previously thought and older also than the so‐called earliest ‘primitive’ and typical microblade tools found at Zhiyu (∼31–39 ka cal BP) and Youfang. These new ages for human occupation of Xibaimaying remove support for the parallel development of the small‐tool and microblade industries in the Nihewan Basin during the Upper Palaeolithic, but reliable age estimates from additional sites are needed to confidently infer the nature of the chronological relationship between these two Upper Palaeolithic industries and the associated toolmakers.

MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 downregulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex. In this study, we demonstrate that miR-9-1 expression increases significantly after the treatment of RUNX1-RUNX1T1 (+) AML cell lines with decitabine (a DNMT inhibitor) and trichostatin A (an HDAC inhibitor). In addition, we show that RUNX1-RUNX1T1 triggers the heterochromatic silencing of miR-9-1 by binding to RUNX1-binding sites in the promoter region of miR-9-1 and recruiting chromatin-remodeling enzymes, DNMTs, and HDACs, contributing to hypermethylation of miR-9-1 in t (8; 21) AML. Furthermore, because RUNX1, RUNX1T1, and RUNX1-RUNX1T1 are all regulated by miR-9-1, the silencing of miR-9-1 enhances the oncogenic activity of these genes. Besides, overexpression of miR-9-1 induces differentiation and inhibits proliferation in t (8; 21) AML cell lines. In conclusion, our results indicate a feedback circuitry involving miR-9-1 and RUNX1-RUNX1T1, contributing to leukemogenesis in RUNX1-RUNX1T1 (+) AML cell lines.

The Nihewan Basin in northern China is a key region in East Asia for the study of early human evolution, owing to the abundance of Palaeolithic sites with ages spanning the entire Pleistocene. However, most of the sites assigned to the Middle to Late Pleistocene have not been dated or are poorly dated, due to the lack of suitable numerical dating techniques. Optically stimulated luminescence (OSL) dating of quartz grains is commonly restricted to deposits younger than~200 ka, but recent developments using the infrared stimulated luminescence (IRSL) emissions from grains of potassium-rich feldspar (K-feldspar) offer the potential to date Middle Pleistocene deposits using post-infrared IRSL (pIRIR) signals that do not suffer from 'anomalous fading'. In this paper, we report the first archaeological applications of the recently developed pre-dose multiple elevated temperature pIRIR (pMET-pIRIR) procedures for K-feldspar, which we applied to the sedimentary deposits at one Lower Palaeolithic site (Donggutuo) and one putatively Middle Palaeolithic site (Motianling) in the Nihewan Basin. Equivalent dose (D e ) values were measured, and non-fading signals were identified, using single-aliquot (SAR) and multiplealiquot (MAR) regenerative-dose pMET-pIRIR procedures. For a sample from Donggutuo expected to be in field saturation, the natural pMET-pIRIR signals were consistent with, or close, to the laboratory saturation levels only when the MAR procedure was used. For the samples from Motianling, however, both the SAR and MAR procedures could be applied and these yielded indistinguishable D e estimates. Our study shows that D e values of up to 1500 Gy (or possibly 2000 Gy) can be measured using pMET-pIRIR procedures, corresponding to ages of up to 500 ka (or 650 ka) for deposits with environmental dose rates of~3 Gy/ka, as is typical for this region. Our results also indicate that samples from a single study area (the Nihewan Basin) can respond differently to the same measurement conditions. As regards the archaeology of the Nihewan Basin, we date the upper part of the cultural layer at the Motianling site to 322 ± 33 ka and the underlying culturally sterile deposits to 370 ± 50 ka. These ages challenge the stratigraphic correlation of the stone artefacts to the Middle Palaeolithic and suggest that they should, instead, be assigned to the Lower Palaeolithic. Given this revised chronology, there is clearly a need to reassess the antiquity of other sites in the Nihewan Basin that have similarly been assigned previously to the Middle Palaeolithic. The pMET-pIRIR procedures tested in this paper show great promise as suitable chronometers for this task, and should be able to provide a timeline for human evolution and activities extending over the last half-million years in this key region of East Asia.

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