The relationship between transcription and the 3D chromatin structure is debated. Multiple studies have shown that transcription affects global Cohesin binding and 3D genome structures. However, ...several other studies have indicated that inhibited transcription does not alter chromatin conformations.
We provide the most comprehensive evidence to date to demonstrate that transcription plays a relatively modest role in organizing the local, small-scale chromatin structures in mammalian cells. We show degraded Pol I, Pol II, and Pol III proteins in mESCs cause few or no changes in large-scale 3D chromatin structures, selected RNA polymerases with a high abundance of binding sites or active promoter-associated interactions appear to be relatively more affected after the degradation, transcription inhibition alters local, small loop domains, as indicated by high-resolution chromatin interaction maps, and loops with bound Pol II but without Cohesin or CTCF are identified and found to be largely unchanged after transcription inhibition. Interestingly, Pol II depletion for a longer time significantly affects the chromatin accessibility and Cohesin occupancy, suggesting that RNA polymerases are capable of affecting the 3D genome indirectly. These direct and indirect effects explain the previous inconsistent findings on the influence of transcription inhibition on the 3D genome.
We conclude that Pol I, Pol II, and Pol III loss alters local, small-scale chromatin interactions in mammalian cells, suggesting that the 3D chromatin structures are pre-established and relatively stable.
Image-based virtual try-on provides customers with convenient online clothes selections by transferring garments onto a reference person. Despite the emergence of several solutions to generate ...photo-realistic images and adapt to complex poses, controlling clothing length remains a challenge. We argue that the clothing reconstruction did not consider clothing length information, which results in clothing length being uncontrollable in most virtual try-on methods. To overcome this limitation, a novel clothing-agnostic person representation is proposed, which eliminates clothing information and quantifies clothing length as a numerical value. A new segmentation generator is designed to predict try-on segmentation maps of any length conditioned on this representation. Moreover, we correct two inaccurate labels, which enables our model to generate a wider range of garment interactions in images, such as the top tucked into or worn over the bottom, as well as the top and bottom worn separately without intersecting. Extensive experiments demonstrate that our method achieves the goal of continuous clothing length control and generates photo-realistic images with fine details that outperform most baseline methods in terms of quantitative and qualitative metrics.
Mammalian cells have three types of RNA polymerases (Pols), Pol I, II, and III. However, the extent to which these polymerases are cross-regulated and the underlying mechanisms remain unclear.
We ...employ genome-wide profiling after acute depletion of Pol I, Pol II, or Pol III to assess cross-regulatory effects between these Pols. We find that these enzymes mainly affect the transcription of their own target genes, while certain genes are transcribed by the other polymerases. Importantly, the most active type of crosstalk is exemplified by the fact that Pol III depletion affects Pol II transcription. Pol II genes with transcription changes upon Pol III depletion are enriched in diverse cellular functions, and Pol III binding sites are found near their promoters. However, these Pol III binding sites do not correspond to transfer RNAs. Moreover, we demonstrate that Pol III regulates Pol II transcription and chromatin binding of the facilitates chromatin transcription (FACT) complex to alter local chromatin structures, which in turn affects the Pol II transcription rate.
Our results support a model suggesting that RNA polymerases show cross-regulatory effects: Pol III affects local chromatin structures and the FACT-Pol II axis to regulate the Pol II transcription rate at certain gene loci. This study provides a new perspective for understanding the dysregulation of Pol III in various tissues affected by developmental diseases.
An innovative, ternary nanocomposite composed of overoxidized poly(3,4-ethylenedioxythiophene) (OPEDOT), gold nanoparticles (AuNPs), and electrochemically reduced graphene oxide (ERGO) was prepared ...on a glassy carbon electrode (GCE) (OPEDOT–AuNPs–ERGO/GCE) through homogeneous chemical reactions and heterogeneous electrochemical methods. The morphology, composition, and structure of this nanocomposite were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The electrochemical properties of the OPEDOT–AuNPs–ERGO/GCE were investigated by cyclic voltammetry using potassium ferricyanide and hexaammineruthenium(III) chloride redox probe systems. This modified electrode shows excellent electro-catalytic activity for dopamine (DA) and uric acid (UA) under physiological pH conditions, but inhibits the oxidation of ascorbic acid (AA). Linear voltammetric responses were obtained when DA concentrations of approximately 4.0–100 μM and UA concentrations of approximately 20–100 μM were used. The detection limits (S/N=3) for DA and UA were 1.0 and 5.0 μM, respectively, under physiological conditions and in the presence of 1.0 mM of AA. This developed method was applied to the simultaneous detection of DA and UA in human urine, where satisfactory recoveries from 96.7% to 105.0% were observed. This work demonstrates that the developed OPEDOT–AuNPs–ERGO ternary nanocomposite, with its excellent ion-selectivity and electro-catalytic activity, is a promising candidate for the simultaneous detection of DA and UA in the presence of AA in physiological and pathological studies.
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•Facile preparation of graphene-based hybrid composite OPEDOT–AuNPs–ERGO onto GCE.•The OPEDOT–AuNPs–ERGO/GCE was endued with excellent electrocatalytic activity and ion-selectivity.•The OPEDOT–AuNPs–ERGO/GCE was found highly selective and sensitive determination of DA and UA in the presence of AA.•The method is expected to be applied to the detection of DA and UA under physiological and pathological conditions.
Abstract
RNA polymerase II (Pol II) apparatuses are compartmentalized into transcriptional clusters. Whether protein factors control these clusters remains unknown. In this study, we find that the
A
...TPase-
a
ssociated with diverse cellular
a
ctivities (AAA + ) ATPase RUVBL2 co-occupies promoters with Pol II and various transcription factors. RUVBL2 interacts with unphosphorylated Pol II in chromatin to promote RPB1 carboxy-terminal domain (CTD) clustering and transcription initiation. Rapid depletion of RUVBL2 leads to a decrease in the number of Pol II clusters and inhibits nascent RNA synthesis, and tethering RUVBL2 to an active promoter enhances Pol II clustering at the promoter. We also identify target genes that are directly linked to the RUVBL2-Pol II axis. Many of these genes are hallmarks of cancers and encode proteins with diverse cellular functions. Our results demonstrate an emerging activity for RUVBL2 in regulating Pol II cluster formation in the nucleus.
For the problem of slow convergence of single amplitude constrained iteration in the traditional multi-plane iterative method and phase ambiguity due to the structure of discontinuous phase, a ...composite amplitude constrained iterative phase retrieval algorithm based on cylindrical lens rotation is proposed. This algorithm is used to obtain multiple intensity images by changing the rotation angle of the cylindrical lens, and phase retrieval is achieved by using a composite amplitude constraint. This algorithm not only improves the accuracy of phase retrieval and enhances the convergence of iterations, but also overcomes the problem of blurred phase reconstruction of phase-discontinuous objects.
Utility tunnel is one of the important infrastructures for the planning and building of smart city. It is of great significance to improve the efficiency of maintenance and overhaul of urban ...pipelines. Based on the disadvantages of the design of utility tunnel pipelines and the properties of traditional Wireless Sensors Network (WSN) protocols, the remote hybrid clustering routing protocol (RHCRP) was proposed. This protocol improved the nodes layout and cluster head (CH) election to adapt to the pipeline requirements. By comparing with traditional WSNs (low-energy adaptive clustering hierarchy algorithm (LEACH) and stable election protocol (SEP), etc.), RHCRP effectively prolonged the WSN lifetime by 50% compared with LEACH. RHCRP also to increase the cluster head quantities by 110.8% to LEACH and 57.6% to SEP, respectively. The proposed method is promising in utility tunnel WSN applications.
BACKGROUND Previous studies demonstrated that tendon-derived stem cells (TDSCs) were vital healing cells and that mRNA expression of anti-inflammatory cytokine IL-6 was significantly upregulated in ...injured tendons. The aim of the present study was to investigate the effects of IL-6 on the TDSCs in vitro. MATERIAL AND METHODS TDSCs isolated from the Achilles tendons in SD rats were co-cultured with various concentrations of IL-6. Cell proliferation, cell cycle analysis, quantitative real-time PCR, western blotting analysis, and statistical analysis were used in the study. RESULTS The result showed that IL-6 strongly increased proliferation capability, and induced cell cycle activation and transition into G2/M phase from G1 phase in TDSCs. However, IL-6 treatment strongly inhibited gene expression of Scleraxis, Collagen 1, Tenomodulin, Collagen 3, Early Growth Response Protein 1, Decorin, Lumican, Biglycan and Fibromodulin in TDSCs. It also strongly inhibited protein expression of tendon cell markers like scleraxis, collagen 1, collagen 3, and tenomodulin. IL-6 treatment strongly activated the JAK/Stat3 signaling pathway in TDSCs. Furthermore, WP1066, a JAK/Stat3 signaling pathway inhibitor, abrogated the effects of IL-6 on TDSCs. CONCLUSIONS These findings indicated that IL-6 might exert dual effects on TDSCs in vitro: strongly enhancing their proliferation but inhibiting their tenogenic differentiation via the JAK/Stat3 pathway.
It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis ...participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge.
Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells.
Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.
There is evidence of increased soil organic carbon (SOC) and inorganic carbon (SIC) under fertilization in dry croplands of arid and semi-arid areas. However, not much is known about the responses of ...SOC and SIC in coastal saline − alkaline paddy soils that undergo flooding − draining cycles. Here, we assess the impacts of various combinations of organic and phosphorus fertilization on SOC and SIC and other soil properties in a saline − alkaline paddy field of the Yellow River Delta. Our study showed that organic fertilization resulted in an increase of SOC by 11.9% over 0 − 20 cm and 13.3% over 20 − 100 cm (i.e., 140 − 250 g C m
−2
y
−1
over 0 − 100 cm) whereas phosphorus fertilization only led to a significant increase of SOC in subsoils (or ~ 75 g C m
−2
y
−1
over 0 − 100 cm). There were little differences in SIC over 0 − 20 cm among the treatments; but SIC showed a significant decrease over 20 − 100 cm under organic fertilization combined with lower rate of phosphorus fertilization. However, high rate of phosphorus fertilization combined with organic amendment led to an increase in SIC stock, but a decrease in SOC stock in the subsoil. There was a significant negative relationship between SIC and SOC stocks in this paddy soil. This study demonstrated that fertilization practices could have complex influences on SOC and SIC in saline − alkaline paddy fields due to the flooding − draining cycles that lead to changes in soil conditions.
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