The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, ...located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.
This study aims to investigate the significance of erythropoietin-producing hepatocellular (Eph)A2 expression and the mechanism by which EphA2 is involved in the epithelial-mensenchymal transition ...(EMT) of gastric cancer cells. EphA2 expression levels were upregulated and positively correlated with metastasis and EMT markers in human gastric cancer specimens. Modulation of EphA2 expression levels had distinct effects on cell proliferation, cell cycle, migration, invasion and morphology in the gastric cancer cell lines SGC7901 and AGS in vitro and in vivo. Overexpression of EphA2 resulted in the upregulation of the EMT molecular markers N-cadherin and Snail, as well as the Wnt/β-catenin targets TCF4, Cyclin-D1 and c-Myc, while silencing EphA2 using short hairpin RNA had the opposite effect. Furthermore, inhibition of the Wnt/β-catenin pathway by XAV939 negated the effect of EphA2 overexpression, whereas activation of the Wnt/β-catenin pathway by LiCl impaired the effect of the EphA2 knockdown on EMT. These observations demonstrate that EphA2 upregulation is a common event in gastric cancer specimens that is closely correlated with cancer metastasis and that EphA2 promotes EMT of gastric cancer cells through activation of Wnt/β-catenin signaling.
Many studies have revealed pathways of epigenetic gene silencing by Polycomb repressive complex 2 (PRC2) in vivo, but understanding the underlying molecular mechanisms requires biochemistry. Here we ...analyze interactions of reconstituted human PRC2 with nucleosome complexes. Histone modifications, the H3K27M cancer mutation, and inclusion of JARID2 or EZH1 in the PRC2 complex have unexpectedly minor effects on PRC2-nucleosome binding. Instead, protein-free linker DNA dominates the PRC2-nucleosome interaction. Specificity for CG-rich sequences is consistent with PRC2 occupying CG-rich DNA in vivo. PRC2 preferentially binds methylated DNA regulated by its AEBP2 subunit, suggesting how DNA and histone methylation collaborate to repress chromatin. We find that RNA, known to inhibit PRC2 activity, is not a methyltransferase inhibitor per se. Instead, RNA sequesters PRC2 from nucleosome substrates, because PRC2 binding requires linker DNA, and RNA and DNA binding are mutually exclusive. Together, we provide a model for PRC2 recruitment and an explanation for how actively transcribed genomic regions bind PRC2 but escape silencing.
Aim
To investigate the effect of irrigation on the surface roughness and fatigue resistance of HyFlex and M3 controlled memory (CM) wire nickel‐titanium instruments.
Methodology
Two new files of each ...brand were analysed by atomic force microscopy (AFM). Then, the instruments were dynamically immersed in either 5.25% sodium hypochlorite (NaOCl) or 17% ethylene diamine tetraacetic acid (EDTA) solution for 10 min, followed by AFM analysis. The roughness average (Ra) and root mean square (RMS) values were analysed statistically using an independent sample t‐test. Then, 36 files of each brand were randomly assigned to three groups (n = 12). Group 1 (the control group) was composed of new instruments. Groups 2 and 3 were dynamically immersed in 5.25% NaOCl and 17% EDTA solutions for 10 min, respectively. The number of rotations to failure for various groups was analysed using the one‐way analysis of variance software.
Results
For M3 files, the Ra and RMS values significantly increased (P < 0.05) after the immersion. For the HyFlex file, the Ra and RMS values significantly increased (P < 0.05) only in EDTA, but not (P > 0.05) NaOCl. The resistance to cyclic fatigue of both HyFlex and M3 files did not significantly decrease (P > 0.05) by immersing in 5.25% NaOCl and 17% EDTA solutions.
Conclusions
Except the HyFlex files immersed in NaOCl, the surface roughness of other files exposed to irrigants increased. However, a change in the surface tomography of CM wire instruments caused by contact with irrigants for 10 min did not trigger a decrease in cyclic fatigue resistance.
We present the first results from an ongoing survey for damped Lyman-α systems (DLAs) in the spectra of z > 2 quasars observed in the course of the Baryon Oscillation Spectroscopic Survey (BOSS), ...which is part of the Sloan Digital Sky Survey (SDSS) III. Our full (non-statistical) sample, based on Data Release 9, comprises 12 081 systems with log N(H i) ≥ 20, out of which 6839 have log N(H i) ≥ 20.3. This is the largest DLA sample ever compiled, superseding that from SDSS-II by a factor of seven. Using a statistical sub-sample and estimating systematics from realistic mock data, we probe the N(H i) distribution at ⟨z⟩ = 2.5. Contrary to what is generally believed, the distribution extends beyond 1022 cm-2 with a moderate slope of index ≈−3.5. This result matches the opacity-corrected distribution observed at z = 0 surprisingly well. The cosmological mass density of neutral gas in DLAs is found to be \hbox{$\omegagdla \approx 10^{-3}$}ΩgDLA≈10-3, evolving only mildly over the past 12 billion years.
Theory and evidence converge to suggest perfectionism is a personality construct that matters a great deal and is linked with many consequential outcomes (e.g., depression, eating disorders, suicide, ...marital problems, and procrastination). With the multidimensional perfectionism construct turning 30 years of age, our review critically examines the past and the future of this construct with a focus on the six landmark dimensions of Hewitt and Flett's (1991) and Frost et al.'s (1990) seminal models: Self-oriented perfectionism, other-oriented perfectionism, socially prescribed perfectionism, personal standards, concerns over mistakes, and doubts about actions. Our review considers both what we understand about these dimensions given the extant empirical literature (i.e., known knowns) and areas where gaps exist in our understanding of multidimensional perfectionism and its consequences (i.e., known unknowns). Evidence suggests the core dimensions of Hewitt and Flett's (1991) and Frost et al.'s (1990) trait and attitudinal models of perfectionism, respectively, are neither captured by nor redundant with other well-established predictors. In fact, these perfectionism dimensions appear to represent core vulnerability factors that are tied intimately to the development and maintenance of a wide range of maladaptive outcomes.
La théorie et la preuve convergent pour indiquer que le perfectionnisme est un aspect très important de la personnalité qui est lié à plusieurs conséquences (par ex., dépression, troubles alimentaires, suicide, problèmes conjugaux et procrastination). À l'occasion des 30 ans de la définition de la construction multidimensionnelle du perfectionnisme, notre revue jette un regard critique sur le passé et l'avenir de cette construction, en se concentrant sur les six dimensions repères des modèles précurseurs de Hewitt et Flett (1991) et de Frost et al. (1990) : le perfectionnisme orienté vers soi, le perfectionnisme orienté vers autrui, le perfectionnisme socialement prescrit, les normes personnelles, les préoccupations relatives à ses erreurs, les doutes relatifs à ses actions. Notre revue tient compte à la fois de ce que nous comprenons de ces dimensions, vu l'étendue de la littérature empirique (les connus connus) et des domaines où notre compréhension du perfectionnisme multidimensionnel et de ses conséquences (les connus inconnus) est lacunaire. Les données indiquent que les dimensions de base des traits et des modèles comportementaux du perfectionnisme établis par Hewitt et Flett (1991) et Frost et al. (1990), respectivement, ne sont jamais relevées ni reprises par d'autres indicateurs bien établis. En fait, ces dimensions du perfectionnisme semblent représenter les facteurs de vulnérabilité de base qui sont intimement reliés au développement et au maintien d'une vaste gamme de comportements inadaptés.
Public Significance Statement
Perfectionism is a personality style consisting of six major components: Self-oriented perfectionism (requiring perfection from the self), socially prescribed perfectionism (the belief that others require perfection from the self), other-oriented perfectionism (requiring perfection from others), personal standards (setting unattainable standards), concern over mistakes, and doubts about actions. This article reviews 30 years of research showing that these perfectionism components are related to various negative psychological, interpersonal, and physical health consequences in people of all ages. Therefore, further research must be conducted to improve the prevention and treatment of perfectionism.
Purpose
The purpose of this study is to evaluate the effectiveness and safety of liraglutide/liraglutide + metformin in overweight/obese women with polycystic ovary syndrome (PCOS).
Methods
The ...related literatures published until April 2021 were searched in PubMed, Cochrane Library, MEDLINE and EmBase.
Results
Six randomized controlled trials of 127 related articles were obtained through searching. Three articles compared liraglutide with metformin, and four articles compared liraglutide combined with metformin with metformin. Our meta-analysis suggests that liraglutide was superior to metformin only in weight loss MD = − 2.74, 95% CI (− 4.29, − 1.18),
P
= 0.0006. Compared with metformin group, the combination group had significant advantages in weight loss MD = − 3.81, 95% CI (− 5.16, − 2.46),
P
< 0.001, BMI MD = − 2.59, 95% CI (− 3.12, − 2.07),
P
< 0.001, waist circumference MD = − 6.26, 95% CI (− 7.79, − 4.72),
P
< 0.001, fasting blood glucose MD = − 0.59, 95% CI (− 0.74, − 0.44),
P
< 0.001 and fasting insulin MD = − 1.52, 95% CI (− 2.69, − 0.35),
P
= 0.01, while the incidence of adverse reactions was relatively high RR = 2.91, 95% CI (1.55, 5.46),
P
= 0.00009.
Conclusion
The present results indicate that liraglutide and metformin have the similar effects in the treatment of overweight/obese PCOS patients. Liraglutide combined with metformin is more effective than metformin in improving PCOS, but it is necessary to master the correct medication method to reduce the occurrence of adverse reactions.
Humidity is a very important factor in representing the severity of electrostatic discharge (ESD). Low humidity indicates high risk of ESD problems; high humidity indicates low risk of ESD problems. ...Both relative humidity and absolute humidity can represent the level of humidity: which one is more important? The reported measurement result shows that relative humidity is more important in the discharge phase. The qualitative analysis is given.
Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on ...histone H3 (H3K27). Trimethylation at H3K27 (H3K27me3) is associated with transcriptional silencing of developmentally important genes. Intriguingly, H3K27me3 is mutually exclusive with H3K36 trimethylation on the same histone tail. Disruptions in this cross-talk result in aberrant H3K27/H3K36 methylation patterns and altered transcriptional profiles that have been implicated in tumorigenesis and other disease states. Despite their importance, the molecular details of how PRC2 “senses” H3K36 methylation are unclear. We demonstrate that PRC2 is activated in cis by the unmodified side chain of H3K36, and that this activation results in a fivefold increase in the k
cat of its enzymatic activity catalyzing H3K27 methylation compared with activity on a substrate methylated at H3K36. Using a photo-cross-linking MS strategy and histone methyltransferase activity assays on PRC2 mutants, we find that EZH2 contains a specific sensing pocket for the H3K36 methylation state that allows the complex to distinguish between modified and unmodified H3K36 residues, altering enzymatic activity accordingly to preferentially methylate the unmodified nucleosome substrate. We also present evidence that this process may be disrupted in some cases of Weaver syndrome.
Dust particles from the Taklimakan Desert can be lofted vertically up to 10 km due to the unique topography and northeasterly winds associated with certain synoptic conditions. Then they can be ...transported horizontally to regions far downwind by westerlies. We combined data from the Multiangle Imaging Spectroradiometer (MISR) and the Cloud‐Aerosol Lidar with Orthogonal Polarization to investigate the three‐dimensional distribution of dust over the Taklimakan Desert and surrounding areas. During spring and summer, a dust belt with high aerosol optical depths (AOD) extends eastward from the Taklimakan Desert to the Loess Plateau along the Hexi Corridor and southward to the Tibetan Plateau. However, the dust extinction coefficients decrease rapidly from 0.340 km−1 near surface to 0.015 km−1 at 5 km in spring, while the extinction values vary within 0.100 ± 0.020 between the altitudes of 1.6 and 3.5 km and decrease to 0.023 km−1 at 5 km in summer, indicating that dust aerosol is relatively well mixed vertically. We further used MISR daily AOD to identify high‐ and low‐dust days and then analyzed composite difference patterns of temperature, geopotential height, and wind between high‐ and low‐dust days. It was found that although the synoptic situations of spring and summer are quite different, there are two common features: a strong anticyclonic wind anomaly over the Taklimakan at 500 hPa and an enhanced easterly wind over the Tarim Basin at 850 hPa for the two seasons. These conditions are favorable for dust entrainment from the dry desert surface, vertical lofting, and horizontal transport.
Key Points
Taklimakan Desert dust can be lofted up to 10 km due to the unique topographyThe aerosol optical depth is significantly correlated with surface wind speedTwo common synoptic features are favorable for dust emission and transport
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