•PWWP domains have strong binding affinity to histone lysine modified nucleosome.•PWWP domain proteins are associated with chromatin in a PWWP-dependent manner.•The PWWP domain is involved in ...crosstalk between different epigenetic marks.•Mutations in the PWWP domain have been linked to various human diseases.
PWWP domain-containing proteins are often involved in chromatin-associated biological processes, such as transcriptional regulation and DNA repair, and recent studies have shown that the PWWP domain specifies chromatin localization. Mutations in the PWWP domain, a 100–150 amino acid motif, have been linked to various human diseases, emphasizing its importance. Structural studies reveal that PWWP domains possess a conserved aromatic cage for histone methyl-lysine recognition, and synergistically bind both histone and DNA, which contributes to their nucleosome-binding ability and chromatin localization. Furthermore, the PWWP domain often cooperates with other histone and DNA ‘reader’ or ‘modifier’ domains to evoke crosstalk between various epigenetic marks. Here, we discuss these recent advances in understanding the structure and function of the PWWP domain.
Abstract
The Jahn-Teller effect is an essential mechanism of spontaneous symmetry breaking in molecular and solid state systems, and has far-reaching consequences in many fields. Up to now, to ...directly image the onset of Jahn-Teller symmetry breaking remains unreached. Here we employ ultrafast ion-coincidence Coulomb explosion imaging with sub-10 fs resolution and unambiguously image the ultrafast dynamics of Jahn-Teller deformations of
$${{\rm{CH}}}_{4}^{+}$$
CH
4
+
cation in symmetry space. It is unraveled that the Jahn-Teller deformation from
C
3v
to
C
2v
geometries takes a characteristic time of 20 ± 7 fs for this system. Classical and quantum molecular dynamics simulations agree well with the measurement, and reveal dynamics for the build-up of the
C
2v
structure involving complex revival process of multiple vibrational pathways of the
$${{\rm{CH}}}_{4}^{+}$$
CH
4
+
cation.
Improving the green total-factor productivity (GTFP) is a key measure to coordinate industrial development and environmental protection in China. This study adopts the biennial Malmquist–Luenberger ...(BML) productivity index to estimate the GTFP change of China's 34 industrial subsectors covering the period 2005–2015. Subsequently, fixed-effect panel quantile regression is applied to analyze the heterogeneous effects of eight selected influencing factors on China's industrial GTFP change. The results show that China's overall industrial GTFP exhibited an increasing trend during the study period and varied greatly in different sub-sectors. Moreover, technological innovation rather than efficiency promotion was the main contributor to the improvement of industrial GTFP in China. The impact of the scale structure (SS) was significantly positive across the quantiles and maintained a slightly downward trend. The impact of the property rights structure (PTS) was significantly negative and showed an increasing trend across the quantiles. The impact of the energy intensity (EI) slightly increased and was significantly negative at most quantiles. The energy consumption structure (ECS) exhibited an increasing trend and had a significantly negative effect at the middle quantiles. Technological innovation (TI) exerted a significantly positive effect and displayed a downward trend across the quantiles, and it was the most important factor to drive industrial GTFP growth. The “pollution halo” hypothesis and the Porter hypothesis were both verified with a certain range from the analysis of foreign direct investment (FDI) and environmental regulation (ER), as well as the interaction between ER and TI. Our results stress the importance of the heterogeneous effects of these influencing factors on different quantile subsectors when formulating the related measures and policies.
The above figure intuitively illustrates the relationship between the eight influencing factors and industrial green total factor productivity change in China according to the estimation results of the fixed-effect panel quantile regression approach, which visually shows the heterogeneous effects of all influencing factors on China's industrial green total factor productivity. Display omitted
•The biennial Malmquist-Luenberger (BML) index is used to estimate China’s industrial GTFP growth.•The panel quantile regression is employed to investigate the influencing factors of China’s industrial GTFP growth.•Technological progress rather than efficiency promotion is the main contributor to China’s industrial GTFP growth.•The effects of all influencing factors on China’s industrial GTP growth are heterogeneous at different quantiles.
Mixed lineage kinase domain-like protein （Mlkl） was recently found to interact with receptor interacting protein 3 （Rip3） and to be essential for tumor necrosis factor （TNF）-induced programmed ...necrosis （necroptosis） in cultured cell lines. We have generated Mlkl-deficient mice by transcription activator-like effector nucleases （TALENs）-mediated gene disruption and found Mlkl to be dispensable for normal mouse development as well as immune cell develop- ment. Mlkl-deficient mouse embryonic fibroblasts （MEFs） and macrophages both showed resistance to necrotic but not apoptotic stimuli. Mlkl-deficient MEFs and macrophages were indistinguishable from wild-type cells in their abil- ity to activate NF-KB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides （LPS）, respectively. Consis- tently, Mlkl-deficient macrophages and mice exhibited normal interleukin-lp （IL-1β）, IL-6, and TNF production after LPS treatment. Mlkl deficiency protects mice from cerulean-induced acute pancreatitis, a necrosis-related disease, but has no effect on polymicrobial septic shock-induced animal death. Our results provide genetic evidence for the role of Mlkl in necroptosis.
AbstractIgnoring the shotcrete hardening property in tunnel design may lead to an overestimation of the bearing capacity of shotcrete liners and underestimation of tunnel convergence. However, ...accounting for this nonlinear hardening behavior of shotcrete in the tunnel analytical model is difficult because of the complexity of the mathematical derivation. This study aims to establish an analytical model to estimate the influence of the shotcrete hardening property on tunnel response. To overcome this challenge, the shotcrete hardening age was divided into several linear stages, and the corresponding equivalent Young’s modulus in each stage was calculated. A unified time-dependent solution was then proposed for predicting tunnel displacement and shotcrete liner pressure, with the tunnel face advancing effect and the installation delay of the shotcrete liner taken into consideration. The proposed analytical solution was applied to the Rong Jiawan tunnel in China, and the general trend of the analytical results agreed with that of the field data. Finally, a comprehensive parametric investigation including the sensitivity of the division of shotcrete age, geostress, and shotcrete hardening model was conducted based on the analytical model, and some useful recommendations for tunnel design are presented. The outcomes of this research can support tunnel design in similar projects.
•The optimal prices and quantities of new and remanufactured are obtained.•The IR’s channel choice is affected by the remanufacturing cost.•Consumer online reviews positively affects the threshold of ...the remanufacturing cost.•The OEM’s strategy choice depends on the licensing fee and consumer online reviews.
This research builds two-period game models to address the choice issues of the Original Equipment Manufacturer (OEM)’s licensing strategy and the Independent Remanufacturer (IR)’s distribution channel, considering consumer online reviews in a closed-loop supply chain. In both periods, the OEM sells new products by the direct distribution channel. In period 2, the OEM determines the licensing strategy (the fixed or royalty fee) to authourize the IR to remanufacture, and then the IR chooses the distribution channel (direct or indirect) for remanufactured products. Interestingly, our results show that the IR prefers the direct channel when the remanufacturing cost is smaller. And the obtained willingness-to-pay (WTP) from consumer online reviews has a positive impact on the threshold value of the remanufacturing cost. Moreover, we find that the OEM’s licensing strategy choice depends on the sizes of the fixed licensing fee and the obtained WTP. The OEM will choose the royalty licensing strategy to the IR who has chosen the direct channel, when the fixed fee and the obtained WTP are smaller. Finally, we find the optimal royalty fee, numerically examine the impact of the interaction among these factors on consumer surplus and social welfare, and relax the basic assumption to show the robustness of our model.
Circumferential yielding lining is able to tolerate controlled displacements without failure, which has been proven to be an effective solution to large deformation problem in squeezing tunnels. ...However, up to now, there has not been a well-established design method for it. This paper aims to present a detailed analytical computation of support characteristic curve (SCC) for circumferential yielding lining, which is a significant aspect of the implementation of convergence-confinement method (CCM) in tunnel support design. Circumferential yielding lining consists of segmental shotcrete linings and highly deformable elements, and its superior performance mainly depends on the mechanical characteristic of highly deformable element. The deformation behavior of highly deformable element is firstly investigated. Its whole deforming process can be divided into three stages including elastic, yielding and compaction stages. Especially in the compaction stage of highly deformable element, a nonlinear stress–strain relationship can be observed. For mathematical convenience, the stress–strain curve in this period is processed as several linear sub-curves. Then, the reasons for closure of circumferential yielding lining in different stages are explained, and the corresponding accurate equations required for constructing the SCC are provided. Furthermore, this paper carries out two case studies illustrating the application of all equations needed to construct the SCC for circumferential yielding lining, where the reliability and feasibility of theoretical derivation are also well verified. Finally, this paper discusses the sensitivity of sub-division in element compaction stage and the influence of element length on SCC. The outcome of this paper could be used in the design of proper circumferential yielding lining.
Interferons (IFNs) play an important role in immunomodulatory and antiviral functions. IFN-induced necroptosis has been reported in cells deficient in receptor-interacting protein kinase 1 (RIPK1), ...Fas-associated protein with death domain (FADD), or caspase-8, but the mechanism is largely unknown. Here, we report that the DNA-dependent activator of IFN regulatory factors (ZBP1, also known as DAI) is required for both type I (β) and type II (γ) IFN-induced necroptosis. We show that L929 fibroblast cells became susceptible to IFN-induced necroptosis when RIPK1, FADD, or Caspase-8 was genetically deleted, confirming the antinecroptotic role of these proteins in IFN signaling. We found that the pronecroptotic signal from IFN stimulation depends on new protein synthesis and identified ZBP1, an IFN-stimulated gene (ISG) product, as the de novo synthesized protein that triggers necroptosis in IFN-stimulated cells. The N-terminal domain (ND) of ZBP1 is important for ZBP1-ZBP1 homointeraction, and its RHIM domain in the C-terminal region interacts with RIPK3 to initiate RIPK3-dependent necroptosis. The antinecroptotic function of RIPK1, FADD, and caspase-8 in IFN-treated cells is most likely executed by caspase-8-mediated cleavage of RIPK3, since the inhibitory effect on necroptosis was eliminated when the caspase-8 cleavage site in RIPK3 was mutated. ZBP1-mediated necroptosis in IFN-treated cells is likely physiologically relevant, as ZBP1 KO mice were significantly protected against acute systemic inflammatory response syndrome (SIRS) induced by TNF + IFN-γ.
Rheumatoid arthritis is a chronic systemic autoimmune disease characterized by synovial hyperplasia, inflammatory cell infiltration, and proliferation of inflammatory tissue (angiogranuloma). The ...destruction of joints and surrounding tissues eventually causes joint deformities and dysfunction or even loss. The S100 protein family is one of the biggest subtribes in the calcium-binding protein family and has more than 20 members. The overexpression of most S100 proteins in rheumatoid arthritis is closely related to its pathogenesis. This paper reviews the relationship between S100 proteins and the occurrence and development of rheumatoid arthritis. It will provide insights into the development of new clinical diagnostic markers and therapeutic targets for rheumatoid arthritis.
AbstractDeformation control and stability analysis are very important for tunnel construction. Large deformations of the constructed primary support accompanied by lining cracking and spalling ...occurred in the Dongxishan Tunnel located in Chaozhou City, northeastern Guangdong Province, China, posing a serious damage to the tunnel safety. In order to determine the causes of large deformations, comprehensive investigations have been performed by combining field monitoring, laboratory tests, and mechanism analyses. The results show that there have been three main factors resulting in the occurrence of large deformations in the Dongxishan Tunnel: the plastic flow of surrounding rock due to low strength of silty clay, obvious creep behavior, and water-weakening effect of silty clay. Besides, based on the preceding mechanism analyses of large deformations, many countermeasures were proposed during construction, including double row pipe pregrouting reinforcement, strengthening primary support, and timely closing of temporary support. These countermeasures can effectively deal with large deformation problems in the Dongxishan Tunnel from the in situ feedbacks. This paper can provide useful guidance for avoiding the similar anomalies in the following excavation and support of Dongxishan Tunnel.
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