Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laser-assisted microvascular anastomoses can be performed more quickly than sutured anastomoses, yet manifest similar patency rates and tensile strength. This study was undertaken to determine if in vitro laser-assisted microvascular anastomoses could be created between human adult arteries (anterior tibial arteries), human placental arteries, and expanded polytetrafluoroethylene microconduits. A CO2 laser was applied in single or continuous bursts with a matrix of variables encompassing power P = 80 to 160 mW, spot size SS = 150 to 500 microns, and exposure time EXP = 1.0-second continuous exposure (n = 2 each composite setting). The endpoints measured to assess the ability to laser-weld vessels were morphologic appearance by scanning electron microscopy and bursting strength. Scanning electron microscopy revealed apparent fusion of human placental arteries and human adult arteries to expanded polytetrafluoroethylene microconduits at settings of P = 130 mW, SS = 300 microns, and EXP = 1.0 second, though bursting pressure at all settings was less than 10 mmHg. Laser-assisted microvascular anastomoses of human placental artery to human placental artery and human adult artery to human adult artery were successful at this setting, though bursting pressures of anastomoses incorporating placental vessels were significantly weaker than those created with adult tissue. The relative weakness of laser-assisted microvascular anastomoses incorporating placental arteries might be explained by qualitative or quantitative differences in vessel wall collagen, as seen in fetal tissue, and deserves further characterization.
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PMID:Laser-assisted microvascular anastomosis of human adult and placental arteries with expanded polytetrafluoroethylene microconduit. 847 79

Myotonic dystrophy (DM; also known as dystrophia myotonica) is an autosomal dominant disorder that affects the heart, eyes, brain and endocrine system, but the predominant symptoms are neuromuscular, with progressive muscle weakness and wasting. DM presents in two forms, DM1 and DM2, both of which are caused by nucleotide repeat expansions: CTG in the DMPK gene for DM1 and CCTG in ZNF9 (CNBP) for DM2. Previous studies have shown that the mutant mRNAs containing the transcribed CUG or CCUG repeats are retained within the nuclei of cells from individuals with DM, where they bind and sequester the muscleblind-like proteins MBNL1, MBNL2 and MBNL3. It has been proposed that the sequestration of these proteins plays a key role in determining the classic features of DM. However, the functions of each of the three MBNL genes are not completely understood. We have generated a zebrafish knockdown model in which we demonstrate that a lack of mbnl2 function causes morphological abnormalities at the eye, heart, brain and muscle levels, supporting an essential role for mbnl2 during embryonic development. Major features of DM are replicated in our model, including muscle defects and splicing abnormalities. We found that the absence of mbnl2 causes disruption to the organization of myofibrils in skeletal and heart muscle of zebrafish embryos, and a reduction in the amount of both slow and fast muscle fibres. Notably, our findings included altered splicing patterns of two transcripts whose expression is also altered in DM patients: clcn1 and tnnt2. The studies described herein provide broader insight into the functions of MBNL2. They also lend support to the hypothesis that the sequestration of this protein is an important determinant in DM pathophysiology, and imply a direct role of MBNL2 in splicing regulation of specific transcripts, which, when altered, contributes to the DM phenotype.
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PMID:Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy. 2130 39

Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder characterized by muscle weakness, cardiac defects and multiple symptoms and is caused by expanded CTG repeats within the 3' untranslated region of the DMPK gene. In this study, we found abnormal splicing of actin-binding LIM protein 1 (ABLIM1) in skeletal muscles of patients with DM1 and a DM1 mouse model (HSA(LR) ). An exon 11 inclusion isoform is expressed in skeletal muscle and heart of non-DM1 individuals, but not in skeletal muscle of patients with DM1 or other adult human tissues. Moreover, we determined that ABLIM1 splicing is regulated by several splice factors, including MBNL family proteins, CELF1, 2 and 6, and PTBP1, using a cellular splicing assay. MBNL proteins promoted the inclusion of ABLIM1 exon 11, but other proteins and expanded CUG repeats repressed exon 11 of ABLIM1. This result is consistent with the hypothesis that MBNL proteins are trapped by expanded CUG repeats and inactivated in DM1 and that CELF1 is activated in DM1. However, activation of PTBP1 has not been reported in DM1. Our results suggest that the exon 11 inclusion isoform of ABLIM1 may have a muscle-specific function, and its abnormal splicing could be related to muscle symptoms of DM1.
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PMID:ABLIM1 splicing is abnormal in skeletal muscle of patients with DM1 and regulated by MBNL, CELF and PTBP1. 2540 73

Smart grid (SG) application is being used nowadays to meet the demand of increasing power consumption. SG application is considered as a perfect solution for combining renewable energy resources and electrical grid by means of creating a bidirectional communication channel between the two systems. In this paper, three SG applications applicable to renewable energy system, namely, distribution automation (DA), distributed energy system-storage (DER) and electrical vehicle (EV), are investigated in order to study their suitability in Long Term Evolution (LTE) network. To compensate the weakness in the existing scheduling algorithms, a novel bandwidth estimation and allocation technique and a new scheduling algorithm are proposed. The technique allocates available network resources based on application's priority, whereas the algorithm makes scheduling decision based on dynamic weighting factors of multi-criteria to satisfy the demands (delay, past average throughput and instantaneous transmission rate) of quality of service. Finally, the simulation results demonstrate that the proposed mechanism achieves higher throughput, lower delay and lower packet loss rate for DA and DER as well as provide a degree of service for EV. In terms of fairness, the proposed algorithm shows 3%, 7 % and 9% better performance compared to exponential rule (EXP-Rule), modified-largest weighted delay first (M-LWDF) and exponential/PF (EXP/PF), respectively.
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PMID:A novel LTE scheduling algorithm for green technology in smart grid. 2583 Jul 3

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG)n trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUGexp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUGexp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs.
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PMID:Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice. 2862 22

Studies on myotonic dystrophy type 1 (DM1) have led to the RNA-mediated disease model for hereditary disorders caused by noncoding microsatellite expansions. This model proposes that DM1 disease manifestations are caused by a reversion to fetal RNA processing patterns in adult tissues due to the expression of toxic CUG RNA expansions (CUGexp) leading to decreased muscleblind-like, but increased CUGBP1/ETR3-like factor 1 (CELF1), alternative splicing activities. Here, we test this model in vivo, using the mouse HSA LR poly(CUG) model for DM1 and recombinant adeno-associated virus (rAAV)-mediated transduction of specific splicing factors. Surprisingly, systemic overexpression of HNRNPA1, not previously linked to DM1, also shifted DM1-relevant splicing targets to fetal isoforms, resulting in more severe muscle weakness/myopathy as early as 4 to 6 wk posttransduction, whereas rAAV controls were unaffected. Overexpression of HNRNPA1 promotes fetal exon inclusion of representative DM1-relevant splicing targets in differentiated myoblasts, and HITS-CLIP of rAAV-mycHnrnpa1-injected muscle revealed direct interactions of HNRNPA1 with these targets in vivo. Similar to CELF1, HNRNPA1 protein levels decrease during postnatal development, but are elevated in both regenerating mouse muscle and DM1 skeletal muscle. Our studies suggest that CUGexp RNA triggers abnormal expression of multiple nuclear RNA binding proteins, including CELF1 and HNRNPA1, that antagonize MBNL activity to promote fetal splicing patterns.
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PMID:HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy. 3208 92