Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy:An assessment using the mdx model and human muscle

INTRODUCTION/AIMS: Raman spectroscopy is an emerging technique for the evaluation of muscle disease. In this study we evaluate the ability of in vivo intramuscular Raman spectroscopy to detect the effects of voluntary running in the mdx model of Duchenne muscular dystrophy (DMD). We also compare mdx data with muscle spectra from human DMD patients. METHODS: Thirty 90‐day‐old mdx mice were randomly allocated to an exercised group (48‐hour access to a running wheel) and an unexercised group (n = 15 per group). In vivo Raman spectra were collected from both gastrocnemius muscles and histopathological assessment subsequently performed. Raman data were analyzed using principal component analysis–fed linear discriminant analysis (PCA‐LDA). Exercised and unexercised mdx muscle spectra were compared with human DMD samples using cosine similarity. RESULTS: Exercised mice ran an average of 6.5 km over 48 hours, which induced a significant increase in muscle necrosis (P = .03). PCA‐LDA scores were significantly different between the exercised and unexercised groups (P < .0001) and correlated significantly with distance run (P = .01). Raman spectra from exercised mice more closely resembled human spectra than those from unexercised mice. DISCUSSION: Raman spectroscopy provides a readout of the biochemical alterations in muscle in both the mdx mouse and human DMD muscle

Label-free fibre optic Raman spectroscopy with bounded simplex-structured matrix factorization for the serial study of serum in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre (n = 66) and 4 months later (n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant (p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales

Rapid identification of human muscle disease with fibre optic Raman spectroscopy

The diagnosis of muscle disorders (“myopathies”) can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time-consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 27 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71–77%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 74–89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders

Extreme sensitivity of myelinating optic nerve axons in a rodent model of perinatal ischemic injury

Cerebral white matter injury (WMI) is increasingly recognized as a common form of perinatal brain injury that predisposes to cerebral palsy as well as cognitive and learning disabilities. Despite the growing impact of WMI, it is unclear whether common cellular and molecular mechanisms define WMI pathogenesis in preterm and term neonates. Although numerous studies have defined a role for glial vulnerability in WMI, there has been limited study of the susceptibility of immature axons.peer-reviewe

Quality Control of Motor Unit Number Index (MUNIX) Measurements in 6 Muscles in a Single-Subject “Round-Robin” Setup

Background Motor Unit Number Index (MUNIX) is a neurophysiological measure that provides an index of the number of lower motor neurons in a muscle. Its performance across centres in healthy subjects and patients with Amyotrophic Lateral Sclerosis (ALS) has been established, but inter-rater variability between multiple raters in one single subject has not been investigated. Objective To assess reliability in a set of 6 muscles in a single subject among 12 examiners (6 experienced with MUNIX, 6 less experienced) and to determine variables associated with variability of measurements. Methods Twelve raters applied MUNIX in six different muscles (abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB), tibialis anterior (TA), extensor dig. brevis (EDB), abductor hallucis (AH)) twice in one single volunteer on consecutive days. All raters visited at least one training course prior to measurements. Intra- and inter-rater variability as determined by the coefficient of variation (COV) between different raters and their levels of experience with MUNIX were compared. Results Mean intra-rater COV of MUNIX was 14.0% (±6.4) ranging from 5.8 (APB) to 30.3% (EDB). Mean inter-rater COV was 18.1 (±5.4) ranging from 8.0 (BB) to 31.7 (AH). No significant differences of variability between experienced and less experienced raters were detected. Conclusion We provide evidence that quality control for neurophysiological methods can be performed with similar standards as in laboratory medicine. Intra- and inter-rater variability of MUNIX is muscle-dependent and mainly below 20%. Experienced neurophysiologists can easily adopt MUNIX and adequate teaching ensures reliable utilization of this method

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (binaries escorted by orbiting planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (binaries escorted by orbiting planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Funding: This research is supported from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 803193/BEBOP), and by a Leverhulme Trust Research Project Grant (no. RPG-2018-418). ACC acknowledges support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1. PM and NM were supported by STFC grant number ST/S001301/1. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (project SPICE DUNE, grant agreement no. 947634). DJA is supported by UKRI through the STFC (ST/R00384X/1) and EPSRC (EP/X027562/1). AC acknowledge funding from the French ANR under contract number ANR18CE310019 (SPlaSH). This work is supported by the French National Research Agency in the framework of the Investissements d’Avenir program (ANR-15-IDEX-02), through the funding of the ‘Origin of Life’ project of the Grenoble-Alpes University. EW acknowledges support from the ERC Consolidator Grant funding scheme (project ASTEROCHRONOMETRY, grant agreement no. 772293 http://www.asterochronometry.eu). MRS acknowledges support from the UK Science and Technology Facilities Council (ST/T000295/1).Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (Binaries Escorted by Orbiting Planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest-radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries.Peer reviewe

NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

UNLABELLED: β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. CONCLUSION: The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences