During mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. We exploited the M- to G1-phase progression to interrogate the contributions of the ...architectural factor CTCF and the process of transcription to genome re-sculpting in newborn nuclei. Depletion of CTCF during the M- to G1-phase transition alters short-range compartmentalization after mitosis. Chromatin domain boundary re-formation is impaired upon CTCF loss, but a subset of boundaries, characterized by transitions in chromatin states, is established normally. Without CTCF, structural loops fail to form, leading to illegitimate contacts between cis-regulatory elements (CREs). Transient CRE contacts that are normally resolved after telophase persist deeply into G1-phase in CTCF-depleted cells. CTCF loss-associated gains in transcription are often linked to increased, normally illegitimate enhancer-promoter contacts. In contrast, at genes whose expression declines upon CTCF loss, CTCF seems to function as a conventional transcription activator, independent of its architectural role. CTCF-anchored structural loops facilitate formation of CRE loops nested within them, especially those involving weak CREs. Transcription inhibition does not significantly affect global architecture or transcription start site-associated boundaries. However, ongoing transcription contributes considerably to the formation of gene domains, regions of enriched contacts along gene bodies. Notably, gene domains emerge in ana/telophase prior to completion of the first round of transcription, suggesting that epigenetic features in gene bodies contribute to genome reconfiguration prior to transcription. The focus on the de novo formation of nuclear architecture during G1 entry yields insights into the contributions of CTCF and transcription to chromatin architecture dynamics during the mitosis to G1-phase progression.
Controlled encapsulation and pairing of single cells within a confined 3D matrix can enable the replication of the highly ordered cellular structure of human tissues. Microgels with independently ...controlled compartments that can encapsulate cells within separately confined hydrogel matrices would provide precise control over the route of pairing single cells. Here, a one‐step microfluidic method is presented to generate monodisperse multicompartment microgels that can be used as a 3D matrix to pair single cells in a highly biocompatible manner. A method is presented to induce microgels formation on chip, followed by direct extraction of the microgels from oil phase, thereby avoiding prolonged exposure of the microgels to the oil. It is further demonstrated that by entrapping stem cells with niche cells within separate but adjacent compartments of the microgels, it can create complex stem cell niche microenvironments in a controlled manner, which can serve as a useful tool for the study of cell–cell interactions. This microfluidic technique represents a significant step toward high‐throughput single cells encapsulation and pairing for the study of intercellular communications at single cell level, which is of significant importance for cell biology, stem cell therapy, and tissue engineering.
A microfluidic method for high‐throughput fabrication of multi‐compartment microgels for single cell encapsulation and assembly is reported. Compartmentalized microgels are produced by rapid gelation of hydrogel emulsions containing multiple aqueous phases, and immediately transfered to the aqueous phase by destabilizing the oil‐water interface. Furthermore, stem cells and niche cells are assembled using Janus microgels to study the stem cell niche.
We consider a hypersonic vehicle optimal flight control problem. The problem is modeled as an optimal control problem of switched systems (OCPSS), which can become a parameter optimization problem ...(POP). Following that, to achieve the globally optimal solution of the POP, an improved continuous filled function (CFF) algorithm including one adjusting parameter is proposed based on a penalty function, in which the CFF is differentiable, excludes logarithmic terms or exponential terms, and does not require to minimize the cost function. Numerical results show that the proposed algorithm is effective.
Onboard electrostatic suspension inertial sensors are important applications for gravity satellites and space gravitational-wave detection missions, and it is important to suppress noise in the ...measurement signal. Due to the complex coupling between the working space environment and the satellite platform, the process of noise generation is extremely complex, and traditional noise modeling and subtraction methods have certain limitations. With the development of deep learning, applying it to high-precision inertial sensors to improve the signal-to-noise ratio is a practically meaningful task. Since there is a single noise sample and unknown true value in the measured data in orbit, odd-even sub-samplers and periodic sub-samplers are designed to process general signals and periodic signals, and adds reconstruction layers consisting of fully connected layers to the model. Experimental analysis and comparison are conducted based on simulation data, GRACE-FO acceleration data, and Taiji-1 acceleration data. The results show that the deep learning method is superior to traditional data smoothing processing solutions.
Features of higher-order chromatin organization-such as A/B compartments, topologically associating domains and chromatin loops-are temporarily disrupted during mitosis
. Because these structures are ...thought to influence gene regulation, it is important to understand how they are re-established after mitosis. Here we examine the dynamics of chromosome reorganization by Hi-C after mitosis in highly purified, synchronous mouse erythroid cell populations. We observed rapid establishment of A/B compartments, followed by their gradual intensification and expansion. Contact domains form from the 'bottom up'-smaller subTADs are formed initially, followed by convergence into multi-domain TAD structures. CTCF is partially retained on mitotic chromosomes and immediately resumes full binding in ana/telophase. By contrast, cohesin is completely evicted from mitotic chromosomes and regains focal binding at a slower rate. The formation of CTCF/cohesin co-anchored structural loops follows the kinetics of cohesin positioning. Stripe-shaped contact patterns-anchored by CTCF-grow in length, which is consistent with a loop-extrusion process after mitosis. Interactions between cis-regulatory elements can form rapidly, with rates exceeding those of CTCF/cohesin-anchored contacts. Notably, we identified a group of rapidly emerging transient contacts between cis-regulatory elements in ana/telophase that are dissolved upon G1 entry, co-incident with the establishment of inner boundaries or nearby interfering chromatin loops. We also describe the relationship between transcription reactivation and architectural features. Our findings indicate that distinct but mutually influential forces drive post-mitotic chromatin reconfiguration.
Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is ...cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient. To isolate the effect of the HGPS iSMCs, the endothelial layer consisted of human cord blood-derived endothelial progenitor cells (hCB-EPCs) from a separate, healthy donor. TEBVs fabricated from HGPS iSMCs and hCB-EPCs show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis relative to TEBVs fabricated from normal iSMCs or primary MSCs. Additionally, treatment of HGPS TEBVs with the proposed therapeutic Everolimus, increases HGPS TEBV vasoactivity and increases iSMC differentiation in the TEBVs. These results show the ability of this iPSC-derived TEBV to reproduce key features of HGPS and respond to drugs.
Proteinaceous matter is an important component of PM2.5, which can cause adverse health effects and also influence the air quality and climate change. However, there is little attention to high ...time-resolved variations and potential role of aerosol proteins during haze pollution periods. In this study, PM2.5 samples were first collected by a medium flow sampler in autumn and winter in Xi'an, China. Then three high time-resolved monitoring campaigns during haze pollution periods were conducted to determine the evolving characteristics of total protein concentration and explore the interactive relationship between protein and other chemical compositions. The results showed that the average protein concentration in PM2.5 in Xi'an (5.46 ± 3.32 μg m−3) was higher than those in most cities of China, and varied by seasons and air pollution conditions. In particular, the protein concentration in PM2.5 increased with the increase of air quality index (AQI). The continuous variations of aerosol proteins during the haze pollution periods further showed that PM2.5, atmospheric humidity and long-distance air mass transport exerted the significant impacts on the protein components in aerosols. Based on the present observation, it is suggested that aerosol proteins might affect the generation of secondary aerosols under haze weather conditions. The present results may provide a new possible insight into the variations and the role of aerosol proteinaceous matter during the formation and development of haze pollution.
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•The high time-resolved variations of proteins in PM2.5 during haze pollution events was examined.•Protein concentration in PM2.5 increased with the increase of air quality index (AQI).•PM2.5, RH and air transport contributed significantly to the variations in aerosol proteins.•Sources of proteins in PM2.5 were different on haze and non-haze days.•Aerosol proteins may affect the formation of secondary aerosols under haze pollution weather.
Hutchinson–Gilford progeria syndrome (HGPS) is a severe human premature aging disorder caused by a lamin A mutant named progerin. Death occurs at a mean age of 13 y from cardiovascular problems. ...Previous studies revealed loss of vascular smooth muscle cells (SMCs) in the media of large arteries in a patient with HGPS and two mouse models, suggesting a causal connection between the SMC loss and cardiovascular malfunction. However, the mechanisms of how progerin leads to massive SMC loss are unknown. In this study, using SMCs differentiated from HGPS induced pluripotent stem cells, we show that HGPS SMCs exhibit a profound proliferative defect, which is primarily caused by caspase-independent cell death. Importantly, progerin accumulation stimulates a powerful suppression of PARP1 and consequently triggers an activation of the error-prone nonhomologous end joining response. As a result, most HGPS SMCs exhibit prolonged mitosis and die of mitotic catastrophe. This study demonstrates a critical role of PARP1 in mediating SMC loss in patients with HGPS and elucidates a molecular pathway underlying the progressive SMC loss in progeria.
Stable employment is a pivotal foundation for contemporary economic development and transformation. The enhancement of labor contract relationship stability is crucial for the great rejuvenation of ...the Chinese nation. Drawing from civil law and various research materials, this study identifies key factors influencing labor contract stability and posits several research hypotheses. This paper constructs a regression analysis model to examine the relationships between these factors and labor contract stability, where the influencing factors serve as independent variables and the stability of the labor contract relationship acts as the dependent variable. The model’s fit is rigorously evaluated. A preliminary analysis employing Pearson’s correlation coefficient reveals significant correlations between all 14 identified factors and the stability of labor contract relationships, supporting the use of regression analysis. Empirical results from the regression analysis indicate a significant positive impact of education level on labor contract stability (p = 0.031 < 0.05). Similarly, employment income is shown to positively influence labor contract stability (p = 0.009 < 0.05). Apart from education level and urban integration challenges, other identified factors also significantly affect the stability of labor contracts. This research not only advances our understanding of the dynamics influencing labor contract stability but also provides a robust empirical basis for shaping relevant civil law regulations and policies.
Temperature fluctuations affect the performance of high-precision gravitational reference sensors. Due to the limited space and the complex interrelations among sensors, it is not feasible to ...directly measure the temperatures of sensor heads using temperature sensors. Hence, a high-accuracy interpolation method is essential for reconstructing the surface temperature of sensor heads. In this study, we utilized XGBoost-LSTM for sensor head temperature reconstruction, and we analyzed the performance of this method under two simulation scenarios: ground-based and on-orbit. The findings demonstrate that our method achieves a precision that is two orders of magnitude higher than that of conventional interpolation methods and one order of magnitude higher than that of a BP neural network. Additionally, it exhibits remarkable stability and robustness. The reconstruction accuracy of this method meets the requirements for the key payload temperature control precision specified by the Taiji Program, providing data support for subsequent tasks in thermal noise modeling and subtraction.
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