Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A

We describe two brothers with lower facial weakness, highly arched palate, scaphocephaly due to synostosis of the sagittal and metopic sutures, axial hypotonia, proximal muscle weakness, and mild scoliosis. The muscle MRI of the younger sibling revealed a selective pattern of atrophy of the gluteus maximus, adductor magnus and soleus muscles. Muscle biopsy of the younger sibling revealed myofibres with internalized nuclei, myofibrillar disarray, and “corona” fibres. Both affected siblings were found to be compound heterozygous for c.3425G>A (p.Arg1142Gln) and c.1123T>C (p.Cys375Arg) mutations in SCN4A on exome sequencing, and the parents were confirmed carriers of one of the mutations. Electrophysiological characterization of the mutations revealed the Cys375Arg confers full and Arg1142Gln mild partial loss-of-function. Loss of function of the Nav1.4 channel leads to a decrement of the action potential and subsequent reduction of muscle contraction. The unusual muscle biopsy features suggest a more complex pathomechanism, and broaden the phenotype associated with SCN4A mutations

Raman Fingerprints of Atomically Precise Graphene Nanoribbons.

Bottom-up approaches allow the production of ultranarrow and atomically precise graphene nanoribbons (GNRs) with electronic and optical properties controlled by the specific atomic structure. Combining Raman spectroscopy and ab initio simulations, we show that GNR width, edge geometry, and functional groups all influence their Raman spectra. The low-energy spectral region below 1000 cm(-1) is particularly sensitive to edge morphology and functionalization, while the D peak dispersion can be used to uniquely fingerprint the presence of GNRs and differentiates them from other sp(2) carbon nanostructures.We acknowledge funding from: the Alexander von Humboldt Foundation in the framework of the Sofja Kovalevskaja Award, endowed by the Federal Ministry for Education and Research of Germany; the ESF project GOSPEL (Ref. No. 09-EuroGRAPHENE-FP-001); the European Research Council (grant NOC-2D, NANOGRAPH, and Hetero2D); the Italian Ministry of Research through the national projects PRIN-GRAF (Grant No. 20105ZZTSE) and FIRB-FLASHit (Grant No. RBFR12SWOJ); the DFG Priority Program SPP 1459; the Graphene Flagship (Ref. No. CNECT-ICT-604391); the EU project MoQuaS; EPSRC Grants (EP/K01711X/1, EP/K017144/1); the EU grant GENIUS; a Royal Society Wolfson Research Merit Award. Computer time was granted by PRACE at the CINECA Supercomputing Center (Grant No. PRA06 1348), and by the Center for Functional Nanomaterials at Brookhaven National Laboratory, supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under contract number DE-SC0012704.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.nanolett.5b0418

Allylic ionic liquid electrolyte-assisted electrochemical surface passivation of LiCoO2 for advanced, safe lithium-ion batteries

Room-temperature ionic liquid (RTIL) electrolytes have attracted much attention for use in advanced, safe lithium-ion batteries (LIB) owing to their nonvolatility, high conductivity, and great thermal stability. However, LIBs containing RTIL-electrolytes exhibit poor cyclability because electrochemical side reactions cause problematic surface failures of the cathode. Here, we demonstrate that a thin, homogeneous surface film, which is electrochemically generated on LiCoO2 from an RTIL-electrolyte containing an unsaturated substituent on the cation (1-allyl-1-methylpiperidinium bis(trifluoromethanesulfonyl)imide, AMPip-TFSI), can avert undesired side reactions. The derived surface film comprised of a high amount of organic species from the RTIL cations homogenously covered LiCoO2 with a ,25 nm layer and helped suppress unfavorable thermal reactions as well as electrochemical side reactions. The superior performance of the cell containing the AMPip-TFSI electrolyte was further elucidated by surface, electrochemical, and thermal analyses.open1

A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia.

Episodic ataxia type 1 (EA1) is an autosomal dominant channelopathy caused by mutations in KCNA1, which encodes the voltage-gated potassium channel, Kv1.1. Eleven members of an EA family were evaluated with molecular and functional studies. A novel c.746T>G (p.Phe249Cys) missense mutation of KCNA1 segregated in the family members with episodic ataxia, myokymia, and malignant hyperthermia susceptibility. No mutations were found in the known malignant hyperthermia genes RYR1 or CACNA1S. The Phe249Cys-Kv1.1 channels did not show any currents upon functional expression, confirming a pathogenic role of the mutation. Malignant hyperthermia may be a presentation of KCNA1 mutations, which has significant implications for the clinical care of these patients and illustrates the phenotypic heterogeneity of KCNA1 mutations

Ceramic on ceramic bearing fractures in total hip arthroplasty : an analysis of data from the national joint registry

Aims: Ceramic-on-ceramic (CoC) bearings in total hip arthroplasty (THA) are commonly used but concerns exist regarding ceramic fracture. This study aims to report the risk of revision for fracture of modern CoC bearings and identify factors that might influence this risk, using data from the National Joint Registry (NJR). Patients and Methods: We analysed data on 111,681 primary CoC THA’s and 182 linked revisions for bearing fracture recorded in NJR. We used implant codes to identify ceramic bearing composition and generated Kaplan-Meier estimates for implant survivorship. Logistic regression analyses were performed for implant size and patient specific variables to determine any associated risks for revision. Results: 99.8% of bearings were CeramTec Biolox® products. Revisions for fracture were linked to 7 of 79,442 (0.009%) Biolox® Delta heads, 38 of 31,982 (0.119%) Biolox® Forte heads, 101 of 80,170 (0.126%) Biolox® Delta liners and 35 of 31,258 (0.112%) Biolox® Forte liners. Regression analysis of implant size revealed smaller heads had significantly higher odds of fracture (χ2=68.0, p<0.0001). The highest fracture risk were observed in the 28mm Biolox® Forte subgroup (0.382%). There were no fractures in the 40mm head group for either ceramic type. Liner thickness was not predictive of fracture (p=0.67). BMI was independently associated with revision for both head fractures (OR 1.09 per unit increase, p=0.031) and liner fractures (OR 1.06 per unit increase, p=0.006). Conclusions: We report the largest study of CoC bearing fractures to date. The risk of revision for CoC bearing fracture is very low, however previous studies have underestimated this risk. There is good evidence that the latest generation of ceramic has greatly reduced the odds of head fracture but not of liner fracture. Small head size and high patient BMI are associated with an increased risk of ceramic bearing fracture

Dengue virus neutralizing antibody levels associated with protection from infection in Thai cluster studies

BACKGROUND: Long-term homologous and temporary heterologous protection from dengue virus (DENV) infection may be mediated by neutralizing antibodies. However, neutralizing antibody titers (NTs) have not been clearly associated with protection from infection. METHODOLOGY/PRINCIPAL FINDINGS: Data from two geographic cluster studies conducted in Kamphaeng Phet, Thailand were used for this analysis. In the first study (2004-2007), cluster investigations of 100-meter radius were triggered by DENV-infected index cases from a concurrent prospective cohort. Subjects between 6 months and 15 years old were evaluated for DENV infection at days 0 and 15 by DENV PCR and IgM ELISA. In the second study (2009-2012), clusters of 200-meter radius were triggered by DENV-infected index cases admitted to the provincial hospital. Subjects of any age 6 months and older were evaluated for DENV infection at days 0 and 14. In both studies, subjects who were DENV PCR positive at day 14/15 were considered to have been susceptible on day 0. Comparison subjects from houses in which someone had documented DENV infection, but the subject remained DENV negative at days 0 and 14/15, were considered non-susceptible. Day 0 samples were presumed to be from just before virus exposure, and underwent plaque reduction neutralization testing (PRNT). Seventeen susceptible (six DENV-1, five DENV-2, and six DENV-4), and 32 non-susceptible (13 exposed to DENV-1, 10 DENV-2, and 9 DENV-4) subjects were evaluated. Comparing subjects exposed to the same serotype, receiver operating characteristic (ROC) curves identified homotypic PRNT titers of 11, 323 and 16 for DENV-1, -2 and -4, respectively, to differentiate susceptible from non-susceptible subjects. CONCLUSIONS/SIGNIFICANCE: PRNT titers were associated with protection from infection by DENV-1, -2 and -4. Protective NTs appeared to be serotype-dependent and may be higher for DENV-2 than other serotypes. These findings are relevant for both dengue epidemiology studies and vaccine development efforts

Serotype-Specific Differences in the Risk of Dengue Hemorrhagic Fever: An Analysis of Data Collected in Bangkok, Thailand from 1994 to 2006

The four dengue viruses (DENV) represent the most common human arbovirus infections in the world and are currently a challenging problem, particularly in the tropical and subtropical regions of Asia and the Americas. Infection with DENV may produce symptoms of varying severity. While access to care, appropriate interventions, host genetic factors, and previous exposure to DENV are all known to affect the outcome of the infection, it is not entirely understood why some individuals develop more severe disease. It has been hypothesized that the four dengue serotypes differ in disease severity and clinical manifestations. This analysis assessed whether there were significant differences in severity of disease caused by the dengue serotypes in a pediatric population in Thailand. We found significant and non-significant correlations between dengue serotype 2 infection and more severe dengue disease. We also found that individual serotypes varied in disease severity between study years, perhaps supporting the hypothesis that the particular sequences of primary and secondary DENV infections influence disease severity

An Approach Merging the IDM-Related Knowledge

Patents are one of the main innovation knowledge sources for engineers and companies. Inventive Design Method (IDM) – results from a research that extends from TRIZ and contains formal knowledge description components using ontologies, such as problems, partial solutions, and parameters. In this paper, we introduce IDM-Similar model that extends existing research work in IDM-related knowledge. A neural network named Word2vec and cosine similarity approach are used to build this model to compute the similarity among problems in wide range domains’ patents covering from the chemistry to mechanics and the computer to physics. Our model assumes that a partial solution of a patent could be used to solve the problem of another patent from a different domain if these two problems are similar enough. Experiments show that our model is a promising alternative to classical TRIZ for engineers to associate their problems in a field to solutions from patents of another field. Consequently, the step dedicated to solution concepts ideation is improved using our work

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies