93 research outputs found
Insights into Electrolytic Pre Lithiation A Thorough Analysis Using Silicon Thin Film Anodes
Pre lithiation via electrolysis, herein defined as electrolytic pre lithiation, using cost efficient electrolytes based on lithium chloride LiCl , is successfully demonstrated as a proof of concept for enabling lithium ion battery full cells with high silicon content negative electrodes. An electrolyte for pre lithiation based on amp; 947; butyrolactone and LiCl is optimized using boron containing additives lithium bis oxalato borate, lithium difluoro oxalate borate and CO2 with respect to the formation of a protective solid electrolyte interphase SEI on silicon thin films as model electrodes. Reversible lithiation in Si Li metal cells is demonstrated with Coulombic efficiencies CEff of 95 96 for optimized electrolytes comparable to 1 m LiPF6 EC EMC 3 7. Formation of an effective SEI is shown by cyclic voltammetry and X ray photoelectron spectroscopy XPS . electrolytic pre lithiation experiments show that notable amounts of the gaseous product Cl2 dissolve in the electrolyte leading to a self discharge Cl2 Cl amp; 8722; shuttle mechanism between the electrodes lowering pre lithiation efficiency and causing current collector corrosion. However, no significant degradation of the Si active material and the SEI due to contact with elemental chlorine is found by SEM, impedance, and XPS. In NCM111 Si full cells, the capacity retention in the 100th cycle can be significantly increased from 54 to 78 by electrolytic pre lithiation, compared to reference cells without pre lithiation of S
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TRIM32 Regulates Skeletal Muscle Stem Cell Differentiation and Is Necessary for Normal Adult Muscle Regeneration
Limb girdle muscular dystrophy type 2H (LGMD2H) is an inherited autosomal recessive disease of skeletal muscle caused by a mutation in the TRIM32 gene. Currently its pathogenesis is entirely unclear. Typically the regeneration process of adult skeletal muscle during growth or following injury is controlled by a tissue specific stem cell population termed satellite cells. Given that TRIM32 regulates the fate of mammalian neural progenitor cells through controlling their differentiation, we asked whether TRIM32 could also be essential for the regulation of myogenic stem cells. Here we demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, we show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly we show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. Our studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H
Erratum to: Mutation screening in 86 known X-linked mental retardation genes by droplet-based multiplex PCR and massive parallel sequencing
Item does not contain fulltext[This corrects the article DOI: 10.1007/s11568-010-9137-y.].1 december 200
Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening
Background: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics an
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases
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