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Background and ObjectivesIgG4 autoantibodies to neurofascin-155 (Nfasc155) are associated with a subgroup of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), currently named autoimmune nodopathy. We previously demonstrated that those antibodies alter conduction along myelinated axons by inducing Nfasc155 depletion and paranode destruction. In blood, IgG4 have the potency to exchange their moiety with other unrelated IgG4 through a process called Fab-arm exchange (FAE). This process results in functionally monovalent antibodies and may affect the pathogenicity of autoantibodies. Here, we examined this issue and whether FAE is beneficial or detrimental for Nfasc155 autoimmune nodopathy.MethodsThe bivalency and monospecificity of anti-Nfasc155 were examined by sandwich ELISA in 10 reactive patients, 10 unreactive CIDP patients, and 10 healthy controls. FAE was induced in vitro using reduced glutathione and unreactive IgG4, and the ratio of the κ:λ light chain was monitored. To determine the pathogenic potential of bivalent anti-Nfasc155 IgG4, autoantibodies derived from patients were enzymatically cleaved into monovalent Fab and bivalent F(ab’)2 or swapped with unreactive IgG4 and then were injected in neonatal animals.ResultsMonospecific bivalent IgG4 against Nfasc155 were detected in the serum of all reactive patients, indicating that a fraction of IgG4 have not undergone FAE in situ. These IgG4 were, nonetheless, capable of engaging into FAE with unreactive IgG4 in vitro, and this decreased the levels of monospecific antibodies and modulated the ratio of the κ:λ light chain. When injected in animals, monovalent anti-Nfasc155 Fab did not alter the formation of paranodes; by contrast, both native anti-Nfasc155 IgG4 and F(ab’)2 fragments strongly impaired paranode formation. The promotion of FAE with unreactive IgG4 also strongly diminished the pathogenic potential of anti-Nfasc155 IgG4 in animals and decreased IgG4 clustering on Schwann cells.DiscussionOur findings demonstrate that monospecific and bivalent anti-Nfasc155 IgG4 are detected in patients and that those autoantibodies are the pathogenic ones. The transformation of anti-Nfasc155 IgG4 into monovalent Fab or functionally monovalent IgG4 through FAE strongly decreases paranodal alterations. Bivalency thus appears crucial for Nfasc155 clustering and paranode destruction.

Perturbation of the endoplasmic reticulum (ER), a central organelle of the cell, can have critical consequences for cellular homeostasis. An elaborate surveillance system known as ER quality control ensures that cells can respond and adapt to stress via the unfolded protein response (UPR) and that only correctly assembled proteins reach their destination. Interestingly, several bacterial pathogens hijack the ER to establish an infection. However, it remains poorly understood how bacterial pathogens exploit ER quality-control functions to complete their intracellular cycle. Brucella spp. replicate extensively within an ER-derived niche, which evolves into specialized vacuoles suited for exit from infected cells. Here we present Brucella-secreted protein L (BspL), a Brucella abortus effector that interacts with Herp, a central component of the ER-associated degradation (ERAD) machinery. We found that BspL enhances ERAD at the late stages of the infection. BspL targeting of Herp and ERAD allows tight control of the kinetics of autophagic Brucella-containing vacuole formation, delaying the last step of its intracellular cycle and cell-to-cell spread. This study highlights a mechanism by which a bacterial pathogen hijacks ERAD components for fine regulation of its intracellular trafficking.

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26Perturbation of endoplasmic reticulum (ER) functions can have critical consequences for 27 cellular homeostasis. An elaborate surveillance system known as ER quality control (ERQC) 28 ensures that only correctly assembled proteins reach their destination. Persistence of 29 misfolded or improperly matured proteins upregulates the unfolded protein response (UPR) to 30 cope with stress, activates ER associated degradation (ERAD) for delivery to proteasomes for 31 degradation. We have identified a Brucella abortus type IV secretion system effector called 32BspL that targets Herp, a key component of ERQC and is able to augment ERAD. 33 Modulation of ERQC by BspL results in tight control of the kinetics of autophagic Brucella-34 containing vacuole formation, preventing premature bacterial egress from infected cells. This 35 study highlights how bacterial pathogens may hijack ERAD components for fine regulation of 36 their intracellular trafficking. 37 38

The book Integrated Music Education: Challenges of Teaching and Teachers Training, edited by Markus Cslovjecsek and Madeleine Zulauf (2018), gathers the insights of 18 experts in music education. Their informed reflections on cultural traditions, interdisciplinary approaches, arts integration, and psychology, combined with evidence from recent experiments and studies, conjoin in two convictions: (1) that music education is an "incomparable cultural good" and (2) that students must be prepared to use their knowledge coherently, constructively, and participatively in society.The journey sets out from a Starting Point. Rudolf Künzli, in The School's Disciplinary Learning Scaffold (Chapter 1), begins with a denouncement of the "scaffold" of learning, or the logic of the school as an institution, which, being opposed to everyday life, poses a barrier to learning. The editors then oppose this with The Intertwining of Music, Education, and Integration (Chapter 2), in which they trace the evolution of integrated music education (IME). They compare the effects of simply increasing the time spent on music to a more student-centered model that abolishes the boundaries between the arts and other subjects and opens the way to integrated learning. The reader then embarks on a trip through five "steps" in which the value of IME is appraised from 14 different viewpoints. As they advance along the route, readers will note that the challenging but rewarding teaching practices that are described may require some training. Each step contains an introduction and two or three chapters. In Step 1, Approaching Integrated Music Education by Exploring Distant Horizons, Joan Russell (Chapter 3) travels to Brazil to observe the arts collective Grupo Mundaréu. She muses on the freedom of such groups, which are unconstrained by the usual institutional boundaries, to enrich education. She presents their colorful performances, analyzes the social and cultural contexts, and wonders about the broader feasibility of this model for IME. Ludwig Pesch (Chapter 4) paints an edifying portrait of Carnatic music from South India, from its prehistoric origins to the present day. As the ancient techniques slowly built a foundation of theoretical rules, the music began to be taught using codified instructions, mnemonic pitch syllables, and visual aids. The author envisages this music as an interdisciplinary concept that connects all people. He chronicles the age-old cultural and religious traditions of the music and describes how it is still transmitted through a mishmash of styles that are at once traditional and modern, regional and Westernized. Colleen Richardson (Chapter 5) extolls the richness of interdisciplinarity through a detailed inspection of the aesthetic parallels between the music of Edgard Varèse and the visual art of Marcel Duchamp. The struggles of these iconoclasts as they trampled over the preconceived ideas and 952854P OM0010.1177/0305735620952854Psychology of MusicBook review book-review2020 Book review

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Numerous studies have supported benefits of omega-3 supplementation using Menhaden fish oil (FO) to promote brain maturation and plasticity during critical developmental periods. The goal of this study was to determine sex-specific immediate and delayed impact of adolescent omega-3 supplementation on visuospatial memory and cognitive flexibility. Sixty-four Wistar rats (n = 32 males and females) received daily FO or soybean oil (CSO) supplementation via oral gavage (0.3 mL/100 g body weight) from postnatal day 28–47. The Barnes Maze Test (BMT) was used to measure visuospatial memory and reversal learning trials (RL) determined cognitive flexibility. Juveniles underwent testing immediately after the gavage period, while adults began testing on postnatal day 90. Adult rats showed reduced working memory errors (WME) and gradual decrease in escape latencies compared to juveniles. Importantly, adult FO-supplemented females displayed fewer WME than males, while males’ performance benefited from CSO supplementation. Overall, sex- and supplementation-dependent effects supported a positive impact of FO in female rats only. Our findings support the potential for supplementation limited to the early adolescence period to influence adulthood spatial learning and cognitive flexibility in a sex-specific manner.