Myelin‐associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for ...immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti‐MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off‐label immunotherapy is common, there are currently no proven effective disease‐modifying therapeutics, and most patients experience slow accumulation of disability over years and decades. The typically slowly progressive nature of this neuropathy presents unique challenges when trying to find effective anti‐MAG therapeutic agents. Drug development has also been hampered by the lack of validated outcome measures that can detect clinically meaningful changes in a reasonable amount of time as well as by the lack of disease activity biomarkers. In this invited review, we provide an update on the state of clinicometric outcome measures and disease activity biomarkers in anti‐MAG neuropathy. We highlight the insensitivity of widely used existing clinicometric outcome measures such as the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as well as the INCAT sensory subscore in anti‐MAG neuropathy, referencing the two previous negative randomized controlled clinical trials evaluating rituximab. We then discuss newly emerging candidate therapeutic agents, including tyrosine kinase inhibitors and enhanced B‐cell–depleting agents, among others. We conclude with a practical approach to the evaluation and management of anti‐MAG neuropathy patients.
A large number of microbial genomes have already been identified from the human gut microbiome, but the understanding of the role of the low-abundance species at the individual level remains ...challenging, largely due to the relatively shallow sequencing depth used in most studies. To improve genome assembling performance, a HiSeq-PacBio hybrid, ultra-deep metagenomic sequencing approach was used to reconstruct metagenomic-assembled genomes (MAGs) from 12 fecal samples. Such approach combined third-generation sequencing with ultra-deep second-generation sequencing to improve the sequencing coverage of the low-abundance subpopulation in the gut microbiome. Our study generated a total of 44 megabase-scale scaffolds, achieving four single-scaffolds of complete (circularized, no gaps) MAGs (CMAGs) that were the first circular genomes of their species. Moreover, 475 high-quality MAGs were assembled across all samples. Among them, 234 MAGs were currently uncultured, including 24 MAGs that were not found in any public genome database. Additionally, 287 and 77 MAGs were classified as low-abundance (0.1-1%) and extra-low-abundance (<0.1%) gut species in each individual, respectively. Our results also revealed individual-specific genomic features in the MAG profiles, including microbial genome growth rate, selective pressure, and frequency of chromosomal mobile genetic elements. Finally, thousands of extrachromosomal mobile genetic elements were identified from the metagenomic data, including 5097 bacteriophages and 79 novel plasmid genomes. Overall, our strategy represents an important step toward comprehensive genomic and functional characterization of the human gut microbiome at an individual level.
Increasing evidence shows that the chicken gastrointestinal microbiota has a major effect on the modulation of metabolic functions and is correlated with economic parameters, such as feed efficiency ...and health. Some of these effects derive from the capacity of the chicken to digest carbohydrates and produce energy-rich metabolites such as short-chain fatty acids (SCFA) and from host-microbe interactions. In this study, we utilized information from metagenomic assembled genomes (MAGs) from chicken gastrointestinal tract (GIT) samples, with detailed annotation of carbohydrate-active enzymes (CAZymes) and genes involved in SCFA production, to better understand metabolic potential at different ages. Metagenomic sequencing of 751 chicken GIT samples was performed to reconstruct 155 MAGs, representing species which belong to six phyla, primarily Firmicutes followed by Proteobacteria. MAG diversity significantly (
p
< 0.001) increased with age, with early domination of Lachnospiraceae, followed by other families including Oscillospiraceae. Age-dependent shifts were observed in the abundance of genes involved in CAZyme and SCFA production, exemplified by a significant increase in glycosyltransferases (GTs) and propionic acid production pathways (
p
< 0.05), and a lower abundance of glycoside hydrolases (GHs) (
p
< 0.01). Co-occurrence analysis revealed a large cluster highly interconnected by enzymes from GT2_2 and GH3 families, underscoring their importance in the community. Furthermore, several species were identified as interaction hubs, elucidating associations of key microbes and enzymes that more likely drive temporal changes in the chicken gut microbiota, and providing further insights into the structure of the complex microbial community. This study extends prior efforts on the characterization of the chicken GIT microbiome at the taxonomic and functional levels and lays an important foundation toward better understanding the broiler chicken gut microbiome helping in the identification of modulation opportunities to increase animal health and performance.
Anti-myelin-associated glycoprotein (MAG) neuropathy is mediated by the binding of IgM M-proteins to the human natural killer-1 epitope of several glycoconjugates, including MAG and phosphacan. We ...recently reported that IgM M-proteins with a higher ratio of anti-phosphacan titer to anti-MAG titer (P/M ratio) were associated with a progressive clinical course. Herein, we investigated the temporal variability of the P/M ratio. The results showed that P/M ratios in worsened cases were significantly increased relative to stable or improved cases. Thus, temporal variability in the specificity of IgM M-proteins may be related to the disease course of anti-MAG neuropathy.
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•Δ P/M ratios are higher in a worsened patients than improve or stable patients.•ΔP/M ratios are correlated to ΔINCAT scores.•P/M ratios may be useful as a novel biomarker of anti-MAG neuropathy.
Diagram illustrates the photocatalytic decolorization of MB dye using NiFe2O4/MWCNTs/ZnO photocatalyst under solar light irradiation, the proposed mechanism and the magnetic separation.
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•NiFe2O4/MWCNTs/ZnO nanocomposite is prepared via a hydrothermal and co-precipitation method at 210 °C and 90 °C respectively.•Optical degradation confirms the synergistic effect between the NiFe2O4, the ZnO and the MWCNTs in the photocatalytic process.•Enhanced photocatalytic activity for decolorization of MB dye from aqueous solutions under solar radiation is achieved.•A photocatalyst of good light response, photocatalytic stability, magnetic separation and reproducibility is attained.•Suppressed recombination of electron–hole pairs results in efficient charge separation and enhanced photocatalytic activity.
Novel multifunctional NiFe2O4/MWCNTs/ZnO hybrid nanocomposite has been successfully synthesized via the hydrothermal and the co-precipitation methods at 210 °C and 90 °C, respectively, to be used as a solar radiation driven photocatalytic material. The hybrid nanocomposite exhibits enhanced photocatalytic activity compared to NiFe2O4 and ZnO for decolorization of Methylene Blue (MB) dye -as a model pollutant - from aqueous solutions under solar radiation. Different complementary analytical tools were used to investigate the structural, optical and magnetic properties of the photocatalyst which possess good light response ability, photocatalytic stability, magnetic separation performance and reproducibility. The results from optical degradation confirmed the synergistic effect between the NiFe2O4, the ZnO and the MWCNTs. Suppressed recombination of electron–hole pairs mean more efficient charge separation and enhanced photocatalytic activity. The apparent rate constant (kapp) of the MB decolorization for a duration of 300 min using NiFe2O4/MWCNTs/ZnO, NiFe2O4 and ZnO photocatalysts were found to be 0.00438 min−1, 4.12857E-4 min−1 and 0.002 min−1 respectively. The removal efficiency was also investigated for different pH values. Due to the magnetic properties of the nanocomposite, it was possible to separate it after degradation experiments and hence re-usability is possible. In view of the enhanced solar radiation driven photodegradation, the present composite can present a robust alternative as a solar radiation driven photocatalyst.
Cold Metal Transfer technology has revolutionized the welding of dissimilar metals and thicker materials by producing improved weld bead aesthetics with controlled metal deposition and low ...heat-input. In this study, the process, weld combinations, laser-CMT hybrid welding and applications of CMT welding are critically reviewed. Microstructure and other weld characteristics have been discussed at length for various base metal combinations. Particularly, the welding of aluminium and steel with better results has been possible with CMT Welding. The results reviewed in this article indicate that the CMT-Laser hybrid welding is more preferable to Laser or Laser hybrid welding. CMT welding has found applications in automobile industries, defence sectors and power plants as a method of additive manufacturing.
The close association of myelinated axons and their myelin sheaths involves numerous intercellular molecular interactions. For example, myelin‐associated glycoprotein (MAG) mediates myelin‐to‐axon ...adhesion and signalling via molecules on the axonal surface. However, knowledge about intracellular binding partners of myelin proteins, including MAG, has remained limited. The two splice isoforms of MAG, S‐ and L‐MAG, display distinct cytoplasmic domains and spatiotemporal expression profiles. We used yeast two‐hybrid screening to identify interaction partners of L‐MAG and found the dynein light chain DYNLL1 (also termed dynein light chain 8). DYNLL1 homodimers are known to facilitate dimerization of target proteins. L‐MAG and DYNLL1 associate with high affinity, as confirmed with recombinant proteins in vitro. Structural analyses of the purified complex indicate that the DYNLL1‐binding segment is localized close to the L‐MAG C terminus, next to the Fyn kinase Tyr phosphorylation site. The crystal structure of the complex between DYNLL1 and its binding segment on L‐MAG shows 2 : 2 binding in a parallel arrangement, indicating a heterotetrameric complex. The homology between L‐MAG and previously characterized DYNLL1‐ligands is limited, and some details of binding site interactions are unique for L‐MAG. The structure of the complex between the entire L‐MAG cytoplasmic domain and DYNLL1, as well as that of the extracellular domain of MAG, were modelled based on small‐angle X‐ray scattering data, allowing structural insights into L‐MAG interactions on both membrane surfaces. Our data imply that DYNLL1 dimerizes L‐MAG, but not S‐MAG, through the formation of a specific 2 : 2 heterotetramer. This arrangement is likely to affect, in an isoform‐specific manner, the functions of MAG in adhesion and myelin‐to‐axon signalling.
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We have identified the dynein light chain DYNLL1 as a specific high‐affinity binding partner for the cytoplasmic domain of the large myelin‐associated glycoprotein (L‐MAG) isoform. Our structural data identify L‐MAG as a non‐canonical binding partner of DYNLL1. Heterotetramer formation between two disordered L‐MAG cytoplasmic tails and a homodimer of DYNLL1 provides a means for the isoform‐specific dimerization of L‐MAG. This interaction may regulate the binding properties of the MAG extracellular domain during myelination.
Read the Editorial Highlight for this article on page 712.
Open Science: This manuscript was awarded with the Open Materials Badge.
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Given the significant presence of the carcinogenic Cr(VI) in arc welding fumes from stainless steels, it is also important, in addition to estimating the Cr(VI) levels, to identify Cr(VI) compounds, ...as it throws light on the mechanistic pathways towards fume formation. FTIR data is presented in this paper for arc welding fumes collected from Manual Metal Arc Welding (MMA), Flux Cored Arc Welding (FCAW) and Solid Wire Welding (Metal Inert/ Active Gas Welding MIG/ MAG). For MMA and FCAW samples, clear spectra corresponding to Na, K, dichromates was observed at wave number of around 725-740 cm-1 and at 890-900 cm-1. Chromate species were also observed at around 850-855 cm-1, as was evidence of CrO3 (chromium trioxide) too (950-970 cm-1). The identification of these compounds was done by carefully identifying the Cr-O-Cr anti-symmetric vibrations, the symmetric stretching of the CrO4 tetrahedra, and the stretching vibrations of the planar CrO3 structure for the chromium trioxide. All the above compounds were volatile, and present as nanoparticles in welding fumes, thereby potentially causing significant harm to the welders. Additionally, crystalline phases (Fe-Mn spinels) were also observed through powder XRD, and the data was compared with ion chromatography estimates for Cr(VI) and found to be consistent.
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•Arc welding fumes (MMA, FCAW and MIG/MAG) were analyzed using FTIR.•IR-active modes for Cr(VI) at 800–900 cm−1, e.g., Cr-O-Cr, Cr-O, CrO, CrO4.•Cr(VI) speciates as Chromates, Dichromates and CrO3, and partly as spinels.•Highest levels of Cr(VI) in MMA welding, compared to FCAW, and MIG/MAG.•FTIR is facile, and augments Ion Chromatography, by identifying Cr(VI) species.
Introduction/Aims
Immunoglobulin M neuropathy associated with anti‐myelin‐associated glycoprotein antibody (IgM/anti‐MAG) neuropathy typically presents with chronic, distal‐dominant symmetrical ...sensory or sensorimotor deficits. Ultrasonographic studies of IgM/anti‐MAG neuropathy are limited, and were all performed on Western populations. We aimed to characterize the nerve ultrasonographic features of IgM/anti‐MAG neuropathy in the Japanese population and evaluate whether they differ from the findings of the common subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP).
Methods
In this cross‐sectional study, we retrospectively reviewed medical records and extracted the cross‐sectional areas (CSAs) of C5–C7 cervical nerve roots and median and ulnar nerves of 6 IgM/anti‐MAG neuropathy patients, 10 typical CIDP (t‐CIDP) patients, 5 multifocal CIDP (m‐CIDP) patients, and 17 healthy controls (HCs).
Results
Cervical nerve root CSAs were significantly larger at every examined site on both sides in IgM/anti‐MAG neuropathy than in m‐CIDP and HCs but were comparable to those in t‐CIDP. Peripheral nerve enlargements were greatest at common entrapment sites (ie, wrist and elbow) in IgM/anti‐MAG neuropathy, a pattern shared with t‐CIDP but not with m‐CIDP. The degree of nerve enlargement at entrapment sites compared to non‐entrapment sites was significantly higher in IgM/anti‐MAG neuropathy than in t‐CIDP.
Discussion
Our study delineated the ultrasonographic features of IgM/anti‐MAG neuropathy in the Japanese population and observed similar characteristics to those of t‐CIDP, with subtle differences. Further studies comparing results from various populations are required to optimize the use of nerve ultrasound worldwide.
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