Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

Dynamic Microtubules Promote Synaptic NMDA Receptor-Dependent Spine Enlargement

Most excitatory synaptic terminals in the brain impinge on dendritic spines. We and others have recently shown that dynamic microtubules (MTs) enter spines from the dendritic shaft. However, a direct role for MTs in long-lasting spine plasticity has yet to be demonstrated and it remains unclear whether MT-spine invasions are directly influenced by synaptic activity. Lasting changes in spine morphology and synaptic strength can be triggered by activation of synaptic NMDA receptors (NMDARs) and are associated with learning and memory processes. To determine whether MTs are involved in NMDAR-dependent spine plasticity, we imaged MT dynamics and spine morphology in live mouse hippocampal pyramidal neurons before and after acute activation of synaptic NMDARs. Synaptic NMDAR activation promoted MT-spine invasions and lasting increases in spine size, with invaded spines exhibiting significantly faster and more growth than non-invaded spines. Even individual MT invasions triggered rapid increases in spine size that persisted longer following NMDAR activation. Inhibition of either NMDARs or dynamic MTs blocked NMDAR-dependent spine growth. Together these results demonstrate for the first time that MT-spine invasions are positively regulated by signaling through synaptic NMDARs, and contribute to long-lasting structural changes in targeted spines

Radiation dose reduction with dictionary learning based processing for head CT.

International audience: In CT, ionizing radiation exposure from the scan has attracted much concern from patients and doctors. This work is aimed at improving head CT images from low-dose scans by using a fast Dictionary learning (DL) based post-processing. Both Low-dose CT (LDCT) and Standard-dose CT (SDCT) nonenhanced head images were acquired in head examination from a multi-detector row Siemens Somatom Sensation 16 CT scanner. One hundred patients were involved in the experiments. Two groups of LDCT images were acquired with 50 % (LDCT50 %) and 25 % (LDCT25 %) tube current setting in SDCT. To give quantitative evaluation, Signal to noise ratio (SNR) and Contrast to noise ratio (CNR) were computed from the Hounsfield unit (HU) measurements of GM, WM and CSF tissues. A blinded qualitative analysis was also performed to assess the processed LDCT datasets. Fifty and seventy five percent dose reductions are obtained for the two LDCT groups (LDCT50 %, 1.15 ± 0.1 mSv; LDCT25 %, 0.58 ± 0.1 mSv; SDCT, 2.32 ± 0.1 mSv; P < 0.001). Significant SNR increase over the original LDCT images is observed in the processed LDCT images for all the GM, WM and CSF tissues. Significant GM-WM CNR enhancement is noted in the DL processed LDCT images. Higher SNR and CNR than the reference SDCT images can even be achieved in the processed LDCT50 % and LDCT25 % images. Blinded qualitative review validates the perceptual improvements brought by the proposed approach. Compared to the original LDCT images, the application of DL processing in head CT is associated with a significant improvement of image quality

Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

International audienceCardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) image

CT Metal Artifact Reduction Method Based on Improved Image Segmentation and Sinogram In-Painting

International audienceThe streak artifacts caused by metal implants degrade the image quality and limit the applications of CT imaging. The standard method used to reduce these metallic artifacts often consists of interpolating the missing projection data but the result is often a loss of image quality with additional artifacts in the whole image. This paper proposes a new strategy based on a three-stage process: (1) the application of a large-scale non local means filter (LS-NLM) to suppress the noise and enhance the original CT image, (2) the segmentation of metal artifacts and metallic objects using a mutual information maximized segmentation algorithm (MIMS), (3) a modified exemplar-based in-painting technique to restore the corrupted projection data in sinogram. The final corrected image is then obtained by merging the segmented metallic object image with the filtered back-projection (FBP) reconstructed image from the in-painted sinogram. Quantitative and qualitative experiments have been conducted on both a simulated phantom and clinical CT images and a comparative study has been led with Bal's algorithm that proposed a similar segmentation-based method

Low-dose lung CT processing using weighted intensity averaging over large-scale neighborhoods

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Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation