137 research outputs found

    Analyzing alternative splicing in Alzheimer’s disease postmortem brain: a cell-level perspective

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    Alzheimer’s disease (AD) is a neurodegenerative disease with no effective cure that attacks the brain’s cells resulting in memory loss and changes in behavior and language skills. Alternative splicing is a highly regulated process influenced by specific cell types and has been implicated in age-related disorders such as neurodegenerative diseases. A comprehensive detection of alternative splicing events (ASEs) at the cellular level in postmortem brain tissue can provide valuable insights into AD pathology. Here, we provided cell-level ASEs in postmortem brain tissue by employing bioinformatics pipelines on a bulk RNA sequencing study sorted by cell types and two single-cell RNA sequencing studies from the prefrontal cortex. This comprehensive analysis revealed previously overlooked splicing and expression changes in AD patient brains. Among the observed alterations were changed in the splicing and expression of transcripts associated with chaperones, including CLU in astrocytes and excitatory neurons, PTGDS in astrocytes and endothelial cells, and HSP90AA1 in microglia and tauopathy-afflicted neurons, which were associated with differential expression of the splicing factor DDX5. In addition, novel, unknown transcripts were altered, and structural changes were observed in lncRNAs such as MEG3 in neurons. This work provides a novel strategy to identify the notable ASEs at the cell level in neurodegeneration, which revealed cell type-specific splicing changes in AD. This finding may contribute to interpreting associations between splicing and neurodegenerative disease outcomes

    The Use of Keystone Flaps in Periarticular Wound Closure: A Case Series

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    The Keystone perforator island flap (Keystone flap), is a Type A fasciocutaneous advancement flap, consisting of two V to Y advancement flaps. Skin cancer excision around joints presents a number of reconstructive challenges. Owing to the mobile nature of joints, the optimal periarticular reconstructive option should possess the ability to provide adequate tissue coverage and withstand regional changes in tensile pressures. We report a single-surgeon series of five cases of periarticular keystone flap between 2014 and 2017. Data were collected from operation notes, clinical photography, histopathology, and outpatient clinic records. The indication for keystone flap was skin cancer in all cases (n = 5). The largest defect size post-excision in was 75 mm × 40 mm × 15 mm. All keystone flaps demonstrate a color and cosmetic appearance comparable to adjacent tissue. There were no major postoperative complications including flap failure or impaired range of joint movement in the follow up period. Superficial wound infection occurred postoperatively in one case. This is the first case series to discuss the use of keystone flaps in periarticular wound closure. Locoregional fasciocutaneous wound coverage offered by keystone flaps may alleviate the risks of graft failure, contour defects, and donor site morbidity associated with alternative reconstructive options, with good functional and cosmetic outcomes. We advocate their use as a robust reconstructive option in periarticular areas

    Expression of genes for bone morphogenetic proteins BMP-2, BMP-4 and BMP-6 in various parts of the human skeleton

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    BACKGROUND: Differences in duration of bone healing in various parts of the human skeleton are common experience for orthopaedic surgeons. The reason for these differences is not obvious and not clear.METHODS: In this paper we decided to measure by the use of real-time RT-PCR technique the level of expression of genes for some isoforms of bone morphogenetic proteins (BMPs), whose role is proven in bone formation, bone induction and bone turnover. Seven bone samples recovered from various parts of skeletons from six cadavers of young healthy men who died in traffic accidents were collected. Activity of genes for BMP-2, -4 and -6 was measured by the use of fluorescent SYBR Green I.RESULTS: It was found that expression of m-RNA for BMP-2 and BMP-4 is higher in trabecular bone in epiphyses of long bones, cranial flat bones and corpus mandibulae then in the compact bone of diaphyses of long bones. In all samples examined the expression of m-RNA for BMP-4 was higher than for BMP-2.CONCLUSION: It was shown that m-RNA for BMP-6 is not expressed in the collected samples at all. It is postulated that differences in the level of activation of genes for BMPs is one of the important factors which determine the differences in duration of bone healing of various parts of the human skeleton.Author has checked copyrightDG 16/11/1

    Genome-Wide Association Study for Femoral Neck Bone Geometry

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    Poor femoral neck bone geometry at the femur is an important risk factor for hip fracture. We conducted a genome-wide association study (GWAS) of femoral neck bone geometry, examining approximately 379,000 eligible single-nucleotide polymorphisms (SNPs) in 1000 Caucasians. A common genetic variant, rs7430431 in the receptor transporting protein 3 (RTP3) gene, was identified in strong association with the buckling ratio (BR, P = 1.6 Γ— 10βˆ’7), an index of bone structural instability, and with femoral cortical thickness (CT, P = 1.9 Γ— 10βˆ’6). The RTP3 gene is located in 3p21.31, a region that we found to be linked with CT (LOD = 2.19, P = 6.0 Γ— 10βˆ’4) in 3998 individuals from 434 pedigrees. The replication analyses in 1488 independent Caucasians and 2118 Chinese confirmed the association of rs7430431 to BR and CT (combined P = 7.0 Γ— 10βˆ’3 for BR and P = 1.4 Γ— 10βˆ’2 for CT). In addition, 350 hip fracture patients and 350 healthy control individuals were genotyped to assess the association of the RTP3 gene with the risk of hip fracture. Significant association between a nearby common SNP, rs10514713 of the RTP3 gene, and hip fracture (P = 1.0 Γ— 10βˆ’3) was found. Our observations suggest that RTP3 may be a novel candidate gene for femoral neck bone geometry. Β© 2010 American Society for Bone and Mineral Researc

    My research world

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    This photograph originally appeared in the 2012 Research student photography and image competition held to celebrate National Science Week (11-19 August)
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