In vivo fiber optic raman spectroscopy of muscle in preclinical models of amyotrophic lateral sclerosis and Duchenne muscular dystrophy

Neuromuscular diseases result in muscle weakness, disability, and, in many instances, death. Preclinical models form the bedrock of research into these disorders, and the development of in vivo and potentially translational biomarkers for the accurate identification of disease is crucial. Spontaneous Raman spectroscopy can provide a rapid, label-free, and highly specific molecular fingerprint of tissue, making it an attractive potential biomarker. In this study, we have developed and tested an in vivo intramuscular fiber optic Raman technique in two mouse models of devastating human neuromuscular diseases, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy (SOD1G93A and mdx, respectively). The method identified diseased and healthy muscle with high classification accuracies (area under the receiver operating characteristic curves (AUROC): 0.76–0.92). In addition, changes in diseased muscle over time were also identified (AUROCs 0.89–0.97). Key spectral changes related to proteins and the loss of α-helix protein structure. Importantly, in vivo recording did not cause functional motor impairment and only a limited, resolving tissue injury was seen on high-resolution magnetic resonance imaging. Lastly, we demonstrate that ex vivo muscle from human patients with these conditions produced similar spectra to those observed in mice. We conclude that spontaneous Raman spectroscopy of muscle shows promise as a translational research tool

BcePred: prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties

Abstract. A crucial step in designing of peptide vaccines involves the identification of B-cell epitopes. In past, numerous methods have been developed for predicting continuous B-cell epitopes, most of these methods are based on physico-chemical properties of amino acids. Presently, its difficult to say which residue property or method is better than the others because there is no independent evaluation or benchmarking of existing methods. In this study the performance of various residue properties commonly used in B-cell epitope prediction has been evaluated on a clean dataset. The dataset used in this study consists of 1029 non-redundant B cell epitopes obtained from Bcipep database and equally number of non-epitopes obtained randomly from SWISS-PROT database. The performance of each residue property used in existing methods has been computed at various thresholds on above dataset. The accuracy of prediction based on properties varies between 52.92 % and 57.53%. We have also evaluated the combination of two or more properties as combination of parameters enhance the accuracy of prediction. Based on our analysis we have developed a method for predicting B cell epitopes, which combines four residue properties. The accuracy of this method is 58.70%, which is slightly better than any single residue property. A web server has been developed to predict B cell epitopes in an antigen sequence. The server is accessible fro

The genomic organization of retrotransposons in Brassica oleracea

We have investigated the copy numbers and genomic organization of five representative reverse transcriptase domains from retrotransposons in Brassica oleracea. Two non-homologous Pseudoviridae (Ty1/copia-like) elements, two Metaviridae (Ty3/gypsy-like) elements (one related to the Athila family) and one Retroposinae (LINE) element were hybridized to a gridded BAC library, “BoB”. The results indicated that the individual LTR retrotransposons (copia and gypsy-like) were represented by between 90 and 320 copies in the haploid genome, with only evidence of a single location for the LINE. Sequence analysis of the same elements against genome survey sequence gave estimates of between 60 and 570, but no LINE was found. There was minimal evidence for clustering between any of these retroelements: only half the randomly expected number of BACs hybridized to both LTR-retrotransposon families. Fluorescent in situ hybridization showed that each of the retroelements had a characteristic genomic distribution. Our results suggest there are preferential sites and perhaps control mechanisms for the insertion or excision of different retrotransposon groups

The old, unique C1 chondrite Flensburg – insight into the first processes of aqueous alteration, brecciation, and the diversity of water-bearing parent bodies and lithologies

International audienceOn September 12, 2019 at 12:49:48 (UT) a bolide was observed by hundreds of eye-witnesses from the Netherlands, Germany, Belgium, Denmark and the UK. One day later a small meteorite stone was found by accident in Flensburg. The presence of short-lived cosmogenic radionuclides with half-lives as short as 16 days proves the recent exposure of the found object to cosmic rays in space linking it clearly to the bolide event. An exceptionally short exposure time of ∼5000 years was determined. The 24.5 g stone has a fresh black fusion crust, a low density of <2 g/cm3, and a magnetic susceptibility of logχ = 4.35 (χ in 10−9 m3/kg). The rock consists of relict chondrules and clusters of sulfide and magnetite grains set in a fine-grained matrix. The most abundant phases are phyllosilicates. Carbonates (∼3.9 vol.%) occur as calcites, dolomites, and a Na-rich phase. The relict chondrules (often surrounded by sulfide laths) are free of anhydrous silicates and contain abundant serpentine. Lithic clasts are also surrounded by similar sulfide laths partly intergrown with carbonates. 53Mn-53Cr ages of carbonates in Flensburg indicate that brecciation and contemporaneous formation of the pyrrhotite-carbonate intergrowths by hydrothermal activities occurred no later than 4564.6 ± 1.0 Ma (using the angrite D'Orbigny as the Mn-Cr age anchor). This corresponds to 2.6 ± 1.0 or 3.4 ± 1.0 Ma after formation of CAIs, depending on the exact absolute age of CAIs. This is the oldest dated evidence for brecciation and carbonate formation, which likely occurred during parent body growth and incipient heating due to decay of 26Al.In the three oxygen isotope diagram, Flensburg plots at the 16O-rich end of the CM chondrite field and in the transition field to CV-CK-CR chondrites. The mass-dependent Te isotopic composition of Flensburg is slightly different from mean CM chondrites and is most similar to those of the ungrouped C2 chondrite Tagish Lake. On the other hand, 50Ti and 54Cr isotope anomalies indicate that Flensburg is similar to CM chondrites, as do the ∼10 wt.% H2O of the bulk material. Yet, the bulk Zn, Cu, and Pb concentrations are about 30% lower than those of mean CM chondrites. The He, Ne, and Ar isotopes of Flensburg show no solar wind contribution; its trapped noble gas signature is similar to that of CMs with a slightly lower concentration of 20Netr.Based on the bulk H, C, and N elemental abundances and isotopic compositions, Flensburg is unique among chondrites, because it has the lightest bulk H and N isotopic compositions of any type 1 or 2 chondrite investigated so far. Moreover, the number of soluble organic compounds in Flensburg is even lower than that of the brecciated CI chondrite Orgueil.The extraordinary significance of Flensburg is evident from the observation that it represents the oldest chondrite sample in which the contemporaneous episodes of aqueous alteration and brecciation have been preserved. The characterization of a large variety of carbonaceous chondrites with different alteration histories is important for interpreting returned samples from the OSIRIS-REx and Hayabusa 2 missions