74 research outputs found

    Longitudinal [18F]FDG and [13N]NH3 PET/CT imaging of brain and spinal cord in a canine hemisection spinal cord injury model

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    To further understand the neurological changes induced by spinal cord injury (SCI) in its acute and subacute stages, we evaluated longitudinal changes in glucose and glutamate metabolism in the spinal cord and brain regions of a canine hemisection SCI model. [18F]FDG and [13N]NH3 positron-emission tomography (PET) with computed tomography (CT) was performed before SCI and at 1, 3, 7, 14, and 21 days after SCI. Spinal cord [18F]FDG uptake increased and peaked at 3 days post SCI. Similar changes were observed in the brain regions but were not statistically significant. Compared to the acute phase of SCI, [13N]NH3 uptake increased in the subacute stage and peaked at 7 days post SCI in all analyzed brain regions. But in spinal cord, no [13N]NH3 uptake was detected before SCI when the blood-spinal cord barrier (BSCB) was intact, then gradually increased when the BSCB was damaged after SCI. [13N]NH3 uptake was significantly correlated with plasma levels of the BSCB disruption marker, monocyte chemoattractant protein-1 (MCP-1). Overall, we showed that SCI induced in vivo changes in glucose uptake in both the spinal cord and the examined brain regions, and changes in glutamine synthetase activity in the latter. Moreover, our results suggest that [13N]NH3 PET may serve as a potential method for assessing BSCB permeability in vivo.</div

    Homozygous mutation in DNAAF4 causes primary ciliary dyskinesia in a Chinese family

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    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder that affects the structure and function of motile cilia, leading to classic clinical phenotypes, such as situs inversus, chronic sinusitis, bronchiectasis, repeated pneumonia and infertility. In this study, we diagnosed a female patient with PCD who was born in a consanguineous family through classic clinical manifestations, transmission electron microscopy and immunofluorescence staining. A novel DNAAF4 variant NM_130810: c.1118G&gt;A (p. G373E) was filtered through Whole-exome sequencing. Subsequently, we explored the effect of the mutation on DNAAF4 protein from three aspects: protein expression, stability and interaction with downstream DNAAF2 protein through a series of experiments, such as transfection of plasmids and Co-immunoprecipitation. Finally, we confirmed that the mutation of DNAAF4 lead to PCD by reducing the stability of DNAAF4 protein, but the expression and function of DNAAF4 protein were not affected

    Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes

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    é 2015 Li et al. Background: Kruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood. Methods: Inducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo. A genome-wide RNA-seq analysis was conducted to identify genes regulated by KLF4 in T-ALL cells. Chromatin immunoprecipitation (ChIP) PCR was used to determine direct binding sites of KLF4 in T-ALL cells. Results: Here we reveal that KLF4 induced apoptosis through the BCL2/BCLXL pathway in human T-ALL cell lines and primary T-ALL specimens. In consistence, mice engrafted with KLF4-overexpressing T-ALL cells exhibited prolonged survival. Interestingly, the KLF4-induced apoptosis in T-ALL cells was compromised in xenografts but the invasion capacity of KLF4-expressing T-ALL cells to hosts was dramatically dampened. We found that KLF4 overexpression inhibited T cell-associated genes including NOTCH1, BCL11B, GATA3, and TCF7. Further mechanistic studies revealed that KLF4 directly bound to the promoters of NOTCH1, BCL2, and CXCR4 and suppressed their expression. Additionally, KLF4 induced SUMOylation and degradation of BCL11B. Conclusions: These results suggest that KLF4 as a major transcription factor that suppresses the expression of T-cell associated genes, thus inhibiting T-ALL progression.Link_to_subscribed_fulltex

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Image Segmentation of Cucumber Seedlings Based on Genetic Algorithm

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    To solve the problems of the low target-positioning accuracy and weak algorithm robustness of target-dosing robots in greenhouse environments, an image segmentation method for cucumber seedlings based on a genetic algorithm was proposed. Firstly, images of cucumber seedlings in the greenhouse were collected under different light conditions, and grayscale histograms were used to evaluate the quality of target and background sample images. Secondly, the genetic algorithm was used to determine the optimal coefficient of the graying operator to further expand the difference between the grayscale of the target and background in the grayscale images. Then, the Otsu algorithm was used to perform the fast threshold segmentation of grayscale images to obtain a binary image after coarse segmentation. Finally, morphological processing and noise reduction methods based on area threshold were used to remove the holes and noise from the image, and a binary image with good segmentation was obtained. The proposed method was used to segment 60 sample images, and the experimental results show that under different lighting conditions, the average F1 score of the obtained binary images was over 94.4%, while the average false positive rate remained at about 1.1%, and the image segmentation showed strong robustness. This method can provide new approaches for the accurate identification and positioning of targets as performed by target-dosing robots in a greenhouse environment

    Image Segmentation of Cucumber Seedlings Based on Genetic Algorithm

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    To solve the problems of the low target-positioning accuracy and weak algorithm robustness of target-dosing robots in greenhouse environments, an image segmentation method for cucumber seedlings based on a genetic algorithm was proposed. Firstly, images of cucumber seedlings in the greenhouse were collected under different light conditions, and grayscale histograms were used to evaluate the quality of target and background sample images. Secondly, the genetic algorithm was used to determine the optimal coefficient of the graying operator to further expand the difference between the grayscale of the target and background in the grayscale images. Then, the Otsu algorithm was used to perform the fast threshold segmentation of grayscale images to obtain a binary image after coarse segmentation. Finally, morphological processing and noise reduction methods based on area threshold were used to remove the holes and noise from the image, and a binary image with good segmentation was obtained. The proposed method was used to segment 60 sample images, and the experimental results show that under different lighting conditions, the average F1 score of the obtained binary images was over 94.4%, while the average false positive rate remained at about 1.1%, and the image segmentation showed strong robustness. This method can provide new approaches for the accurate identification and positioning of targets as performed by target-dosing robots in a greenhouse environment

    Phaeosphaeridiols A–C: Three New Compounds from Undescribed <i>Phaeosphaeriaceae</i> sp. SGSF723

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    Fungi in forest litter are diverse as decomposers but natural products from these fungi are rarely investigated, especially for their antimicrobial activities against crop diseases. In this study, fungal isolate SGSF723 with antimicrobial activities was cultured. A multi-gene phylogenetic analysis showed SGSF723 was an undescribed species in the family Phaeosphaeriaceae. By bio-guided assay, three new compounds (Phaeosphaeridiols A–C) and two known compounds were purified from the ethyl acetate extract. The structures of Phaeosphaeridiols A–C were elucidated as 2-(2′-butenyl)-5 (3″-pentene)-1,3-benzenediol (1), 2-(2′-butenyl)-5-(3″S,4″S-pentane diol)-1,3-benzenediol (2), and 3-(4′-(2″-butenyl)-3′,5′-benzenediol phenol)-2-acrylic acid (3) by 2D NMR, HRESIMS, and Mosher’s method. Phaeosphaeridiols A–C exhibited moderate or weak antimicrobial activities against plant pathogens by 96-well plate and spore germination assays
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