Near-infrared photoactivatable control of Ca signaling and optogenetic immunomodulation

The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed Opto-CRAC ) that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded photoactivatable adjuvant to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote control of Ca2+-modulated activities with tailored function

Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation

The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed 'Opto-CRAC') that selectively and remotely controls Ca(2+) oscillations and Ca(2+)-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca(2+)-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded 'photoactivatable adjuvant' to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote and wireless control of Ca(2+)-modulated activities with tailored function. DOI: http://dx.doi.org/10.7554/eLife.10024.00

Roles of Tet-Eleven Translocation(TET) Methylcytosine Dioxygenases in Mammalian Heart Development

DNA methylation and demethylation cycle plays critical roles in spatiotemporally orchestration of gene expression networks during mammalian development and diseases. Ten-eleven translocation (Tet) methylcytosine dioxygenases (Tet1, Tet2 and Tet3) are the major players for mediating DNA demethylation. However, the function of Tet enzymes in cardiac development is still unclear. In this study, we took advantages of the in vitro Tet deficient mouse embryonic stem cell (mESCs) cardiac differentiation model and the cardiac-specific Tet deficient mice models to evaluate Tet mediated epigenetic regulation in heart development. State-of-the-art next generation sequencing (NGS) technologies in combination with cutting-edge bioinformatic analysis and sophisticated histology analysis were applied to uncover the underlying molecular mechanisms. Our data showed that deletion of Tet proteins impaired the cardiac lineage specification during mESCs differentiation. Loss of Tet2 and Tet3 during heart development caused the non-compaction cardiomyopathy (NCC). Tet2 and Tet3 mediated chromatin accessibility enabling chromatin binding of transcription factor Ying-Yang1(YY1), and therefore facilitating enhancer-promoter interactions of genes that are important for cardiac development. In addition, cardiac specific Tet1/2/3 loss-of-function delayed the development of progenitors in the second heart field and blocked their differentiation toward cardiomyocytes, which resulted in severe cardiac development defects, including shorter outflow tract (OFT), atrial septal defect (ASD) and ventricular septal defect (ASD). This study elaborated the crucial roles of Tet mediated DNA demethylation in heart development and provided additional molecular foundation for the prevention and treatment of congenital heart diseases in human

A Boosting SAR Image Despeckling Method Based on Non-Local Weighted Group Low-Rank Representation

In this paper, we propose a boosting synthetic aperture radar (SAR) image despeckling method based on non-local weighted group low-rank representation (WGLRR). The spatial structure information of SAR images leads to the similarity of the patches. Furthermore, the data matrix grouped by the similar patches within the noise-free SAR image is often low-rank. Based on this, we use low-rank representation (LRR) to recover the noise-free group data matrix. To maintain the fidelity of the recovered image, we integrate the corrupted probability of each pixel into the group LRR model as a weight to constrain the fidelity of recovered noise-free patches. Each single patch might belong to several groups, so different estimations of each patch are aggregated with a weighted averaging procedure. The residual image contains signal leftovers due to the imperfect denoising, so we strengthen the signal by leveraging on the availability of the denoised image to suppress noise further. Experimental results on simulated and actual SAR images show the superior performance of the proposed method in terms of objective indicators and of perceived image quality

Remote Sensing Image Fusion Based on Sparse Representation and Guided Filtering

In this paper, a remote sensing image fusion method is presented since sparse representation (SR) has been widely used in image processing, especially for image fusion. Firstly, we used source images to learn the adaptive dictionary, and sparse coefficients were obtained by sparsely coding the source images with the adaptive dictionary. Then, with the help of improved hyperbolic tangent function (tanh) and l 0 − max , we fused these sparse coefficients together. The initial fused image can be obtained by the image fusion method based on SR. To take full advantage of the spatial information of the source images, the fused image based on the spatial domain (SF) was obtained at the same time. Lastly, the final fused image could be reconstructed by guided filtering of the fused image based on SR and SF. Experimental results show that the proposed method outperforms some state-of-the-art methods on visual and quantitative evaluations

A Collaborative Despeckling Method for SAR Images Based on Texture Classification

Speckle is an unavoidable noise-like phenomenon in Synthetic Aperture Radar (SAR) imaging. In order to remove speckle, many despeckling methods have been proposed during the past three decades, including spatial-based methods, transform domain-based methods, and non-local filtering methods. However, SAR images usually contain many different types of regions, including homogeneous and heterogeneous regions. Some filters could despeckle effectively in homogeneous regions but could not preserve structures in heterogeneous regions. Some filters preserve structures well but do not suppress speckle effectively. Following this theory, we design a combination of two state-of-the-art despeckling tools that can overcome their respective shortcomings. In order to select the best filter output for each area in the image, the clustering and Gray Level Co-Occurrence Matrices (GLCM) are used for image classification and weighting, respectively. Clustering and GLCM use the co-registered optical images of SAR images because their structure information is consistent, and the optical images are much cleaner than SAR images. The experimental results on synthetic and real-world SAR images show that our proposed method can provide a better objective performance index under a strong noise level. Subjective visual inspection demonstrates that the proposed method has great potential in preserving structural details and suppressing speckle noise

A SAR Image-Despeckling Method Based on HOSVD Using Tensor Patches

Coherent imaging systems, such as synthetic aperture radar (SAR), often suffer from granular speckle noise due to inherent defects, which can make interpretation challenging. Although numerous despeckling methods have been proposed in the past three decades, SAR image despeckling remains a challenging task. With the extensive use of non-local self-similarity, despeckling methods under the non-local framework have become increasingly mature. However, effectively utilizing patch similarities remains a key problem in SAR image despeckling. This paper proposes a three-dimensional (3D) SAR image despeckling method based on searching for similar patches and applying the high-order singular value decomposition (HOSVD) theory to better utilize the high-dimensional information of similar patches. Specifically, the proposed method extends two-dimensional (2D) to 3D for SAR image despeckling using tensor patches. A new, non-local similar patch-searching measure criterion is used to classify the patches, and similar patches are stacked into 3D tensors. Lastly, the iterative adaptive weighted tensor cyclic approximation is used for SAR image despeckling based on the HOSVD method. Experimental results demonstrate that the proposed method not only effectively reduces speckle noise but also preserves fine details

A potential relationship among beta-defensins haplotype, SOX7 duplication and cardiac defects.

OBJECTIVE: To determine the pathogenesis of a patient born with congenital heart defects, who had appeared normal in prenatal screening. METHODS: In routine prenatal screening, G-banding was performed to analyse the karyotypes of the family and fluorescence in situ hybridization was used to investigate the 22q11.2 deletion in the fetus. After birth, the child was found to be suffering from heart defects by transthoracic echocardiography. In the following study, sequencing was used to search for potential mutations in pivotal genes. SNP-array was employed for fine mapping of the aberrant region and quantitative real-time PCR was used to confirm the results. Furthermore, other patients with a similar phenotype were screened for the same genetic variations. To compare with a control, these variations were also assessed in the general population. RESULTS: The child and his mother each had a region that was deleted in the beta-defensin repeats, which are usually duplicated in the general population. Besides, the child carried a SOX7-gene duplication. While this duplication was not detected in his mother, it was found in two other patients with cardiac defects who also had the similar deletion in the beta-defensin repeats. CONCLUSION: The congenital heart defects of the child were probably caused by a SOX7-gene duplication, which may be a consequence of the partial haplotype of beta-defensin regions at 8p23.1. To our knowledge, this is the first congenital heart defect case found to have the haplotype of beta-defensin and the duplication of SOX7

Finite element analysis of maxillary first molar with mesial-occlusal-distal-palatal defect restored with different post-and-core strategies

Purpose: To explore which restoration strategy generates the most favorable stress distribution in an endodontically-treated maxillary first molar with mesial-occlusal-distal-palatal defect. Methods: Models with one post in palatal canal (PP), each post in palatal and distobuccal canals (PDP), each post in palatal and mesiobuccal canals (PMP), and each post in all canals (PDMP) were established for an endodontically-treated maxillary first molar with mesial-occlusal-distal-palatal defect either with fiber-reinforced composite (FRC) post or gold alloy cast (GAC) post. A 400-N vertical force and a 225-N lateral force were respectively applied. The Mohr-Coulomb stress ratio (σMC ratio) in the residual tooth structure (RTS), the resin cement, and the crowns, the tensile stress (σt) and compressive stress (σc) in the FRC posts, the von-Mises stress ratio (σvM ratio) in the GAC post-and-cores, and the σt and shear stress (σs) at the adhesive interfaces were calculated using finite element analysis. Results: FRC posts generated lower σMC ratio than GAC posts in the RTS (0.3274–0.3643 vs. 0.3399–0.4118). Among the FRC post groups, the PDMP group got the lowest σs at the dentin-post interface (14.92 MPa) and the abutment-crown interface (8.242 MPa) under vertical loading, as well as the lowest σMC ratio in the RTS (0.3381) and the lowest σs at the dentin-post interface (38.00 MPa) under lateral loading. Conclusions: From the point of stress distribution, placing FRC posts in the palatal, distobuccal, and mesiobuccal canals is the optimal strategy in restoring a severely damaged maxillary first molar, provided that lateral occlusal force is reduced

Patients Carrying 9q31.1-q32 Deletion Share Common Features with Cornelia de Lange Syndrome

Background: Cornelia de Lange Syndrome (CdLS) is a rare but severe clinically heterogeneous developmental disorder characterized by facial dysmorphia, growth and cognitive retardation, and abnormalities of limb development. Objectives: To determine the pathogenesis of a patient with CdLS. Methods: We studied a patient with CdLS by whole exome sequencing, karyotyping and Agilent CGH Array. The results were confirmed by quantitative real-time PCR analysis of the patient and her parents. Further comparison of our patient and cases with partially overlapping deletions retrieved from the literature and databases was undertaken. Results: Whole exome sequencing had excluded the mutation of cohesion genes such as NIPBL,SMC1A and SMC3. The result of karyotyping showed a deletion of chromosome 9q31.1-q32 and the result of Agilent CGH Array further displayed a 12.01-Mb region of deletion at chromosome bands 9q31.1-q32. Reported cases with the deletion of 9q31.1-q32 share similar features with our CdLS patient. One of the genes in the deleted region, SMC2, belongs to the Structural Maintenance of Chromosomes (SMC) family and regulates gene expression and DNA repair. Conclusions: Patients carrying the deletion of 9q31.1-q32 showed similar phenotypes with CdLS