Eos Negatively Regulates Human γ-globin Gene Transcription during Erythroid Differentiation

BACKGROUND: Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4), a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: Western blot and quantitative real-time PCR detected a gradual decrease in Eos expression during erythroid differentiation of hemin-induced K562 cells and Epo-induced CD34+ hematopoietic stem/progenitor cells (HPCs). DNA transfection and lentivirus-mediated gene transfer demonstrated that the enforced expression of Eos significantly represses the expression of γ-globin, but not other globin genes, in K562 cells and CD34+ HPCs. Consistent with a direct role of Eos in globin gene regulation, chromatin immunoprecipitaion and dual-luciferase reporter assays identified three discrete sites located in the DNase I hypersensitivity site 3 (HS3) of the β-globin locus control region (LCR), the promoter regions of the Gγ- and Aγ- globin genes, as functional binding sites of Eos protein. A chromosome conformation capture (3C) assay indicated that Eos may repress the interaction between the LCR and the γ-globin gene promoter. In addition, erythroid differentiation was inhibited by enforced expression of Eos in K562 cells and CD34+ HPCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Eos plays an important role in the transcriptional regulation of the γ-globin gene during erythroid differentiation

Radioiodine Labeled Anti-MIF McAb: A Potential Agent for Inflammation Imaging

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with NaI125 by Iodogen method. Animal models were induced in the mice by intramuscular injection of S. aureus, E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of I125-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found in S. aureus group and the lowest was in E. coli group. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders

Correlation of Atomic Cluster Symmetry and Glass-Forming Ability of Metallic Glass

Local structures play a crucial role in glass formation and properties. In addition to topological short-range order, the geometric property of site symmetry is another important but less known characteristic of local structures. It is shown that the observed sharp increase of glass forming ability of Ce70-xAl10Cu20Cox upon Co addition is correlated with a dramatic increase of Al site symmetry, as reflected by decreasing quadrupole frequency measured by 27Al NMR. The result is consistent with the structure model of Al-centered icosahedral clusters as the predominant structural building blocks

PointCAT: Contrastive Adversarial Training for Robust Point Cloud Recognition

Notwithstanding the prominent performance achieved in various applications, point cloud recognition models have often suffered from natural corruptions and adversarial perturbations. In this paper, we delve into boosting the general robustness of point cloud recognition models and propose Point-Cloud Contrastive Adversarial Training (PointCAT). The main intuition of PointCAT is encouraging the target recognition model to narrow the decision gap between clean point clouds and corrupted point clouds. Specifically, we leverage a supervised contrastive loss to facilitate the alignment and uniformity of the hypersphere features extracted by the recognition model, and design a pair of centralizing losses with the dynamic prototype guidance to avoid these features deviating from their belonging category clusters. To provide the more challenging corrupted point clouds, we adversarially train a noise generator along with the recognition model from the scratch, instead of using gradient-based attack as the inner loop like previous adversarial training methods. Comprehensive experiments show that the proposed PointCAT outperforms the baseline methods and dramatically boosts the robustness of different point cloud recognition models, under a variety of corruptions including isotropic point noises, the LiDAR simulated noises, random point dropping and adversarial perturbations

mtDNA-Specific Ultrasensitive Near-Infrared Fluorescent Probe Enables the Differentiation of Healthy and Apoptotic Cells

Mitochondrial DNA (mtDNA) as a class of important genetic material is easily damaged, which can result in a series of metabolic diseases, hereditary disease, and so on. mtDNA is an ultrasensitive indicator for the health of living cells due to the extremely short physiological response time of mtDNA toward damage (ca. 5.0 min). Therefore, the development of specific ultrasensitive fluorescent probes that can in real-time monitor mtDNA in vivo are of great value. With this research, we developed a near-infrared twisted intramolecular charge transfer (TICT) fluorescent probe YON. YON is a thread-like molecule with an A-π-D-π-A structure, based on the dicyanoisophorone fluorophore. The molecular design of YON enabled the specific binding with dsDNA (binding constant (K) = 8.5 × 105 M-1) within 1.3 min. And the appropriate water-oil amphiphilicity makes YON significantly accumulate in the mitochondria, enabling the specific binding to mtDNA. The fluorescence intensity at 640 nm of YON enhanced linearly with increasing concentrations of mtDNA. Dicyanoisophorone as the strong electron-withdrawing group that was introduced into both ends of the molecule resulted in YON being a classic quadrupole, so it could ultrasensitively detect trace mtDNA. The minimum detection limit was 71 ng/mL. Moreover, the large Stokes shift (λex = 435 nm, λem = 640 nm) makes YON suitable for "interference-free"imaging of mtDNA. Therefore, YON was used to monitor trace changes of mtDNA in living cells; more importantly, it could be used to evaluate the health of cells by monitoring microchanges of mtDNA, enabling the ultrasensitive evaluation of apoptosis. </p

InSAR reveals land deformation at Guangzhou and Foshan, China between 2011 and 2017 with COSMO-SkyMed data

Subsidence from groundwater extraction and underground tunnel excavation has been known for more than a decade in Guangzhou and Foshan, but past studies have only monitored the subsidence patterns as far as 2011 using InSAR. In this study, the deformation occurring during the most recent time-period between 2011 and 2017 has been measured using COSMO-SkyMed (CSK) to understand if changes in temporal and spatial patterns of subsidence rates occurred. Using InSAR time-series analysis (TS-InSAR), we found that significant surface displacement rates occurred in the study area varying from -35 mm/year (subsidence) to 10 mm/year (uplift). The 2011-2017 TS-InSAR results were compared to two separate TS-InSAR analyses (2011-2013, and 2013-2017). Our CSK TS-InSAR results are in broad agreement with previous ENVISAT results and levelling data, strengthening our conclusion that localised subsidence phenomena occurs at different locations in Guangzhou and Foshan. A comparison between temporal and spatial patterns of deformations from our TS-InSAR measurements and different land use types in Guangzhou shows that there is no clear relationship between them. Many local scale deformation zones have been identified related to different phenomena. The majority of deformations is related to excessive groundwater extraction for agricultural and industrial purposes but subsidence in areas of subway construction also occurred. Furthermore, a detailed analysis on the sinkhole collapse in early 2018 has been conducted, suggesting that surface loading may be a controlling factor of the subsidence, especially along the road and highway. Roads and highways with similar subsidence phenomenon are identified. Continuous monitoring of the deforming areas identified by our analysis is important to measure the magnitude and spatial pattern of the evolving deformations in order to minimise the risk and hazards of land subsidence

Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated