Loss of supervillin causes myopathy with myofibrillar disorganization and autophagic vacuoles

The muscle specific isoform of the supervillin protein (SV2), encoded by the SVIL gene, is a large sarcolemmal myosin II- and F-actin-binding protein. Supervillin (SV2) binds and co-localizes with costameric dystrophin and binds nebulin, potentially attaching the sarcolemma to myofibrillar Z-lines. Despite its important role in muscle cell physiology suggested by various in vitro studies, there are so far no reports of any human disease caused by SVIL mutations. We here report four patients from two unrelated, consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. All patients showed increased levels of serum creatine kinase but no or minor muscle weakness. Mild cardiac manifestations were observed. Muscle biopsies showed complete loss of large supervillin isoforms in muscle fibres by western blot and immunohistochemical analyses. Light and electron microscopic investigations revealed a structural myopathy with numerous lobulated muscle fibres and considerable myofibrillar alterations with a coarse and irregular intermyofibrillar network. Autophagic vacuoles, as well as frequent and extensive deposits of lipoproteins, including immature lipofuscin, were observed. Several sarcolemma-associated proteins, including dystrophin and sarcoglycans, were partially mis-localized. The results demonstrate the importance of the supervillin (SV2) protein for the structural integrity of muscle fibres in humans and show that recessive loss-of-function mutations in SVIL cause a distinctive and novel myopathy

Nanoflowers Versus Magnetosomes: Comparison Between Two Promising Candidates for Magnetic Hyperthermia Therapy

Magnetic Fluid Hyperthermia mediated by iron oxide nanoparticles is one of the most promising therapies for cancer treatment. Among the different candidates, magnetite and maghemite nanoparticles have revealed to be some of the most promising candidates due to both their performance and their biocompatibility. Nonetheless, up to date, the literature comparing the heating ef ciency of magnetite and maghemite nanoparticles of similar size is scarce. To ll this gap, here we provide a comparison between commercial Synomag Nano owers (pure maghemite) and bacterial magnetosomes (pure magnetite) synthesized by the magnetotactic bacterium Magnetospirillum gryphiswaldense of hDi 40 45 nm. Both types of nanoparticles exhibit a high degree of crystallinity and an excellent degree of chemical purity and stability. The structural and magnetic properties in both nanoparticle ensembles have been studied by means of X Ray Diffraction, Transmission Electron Microscopy, X Ray Absorption Spectroscopy, and SQUID magnetometry. The heating ef ciency has been analyzed in both systems using AC magnetometry at several eld amplitudes (0 88 mT) and frequencies (130, 300, and 530 kHz).This work was supported in part by the Spanish "Ministerio de Ciencia, Investigación y Universidades'' under Project MAT2017-83631-C3-R, and in part by the Nanotechnology in Translational Hyperthermia (HIPERNANO) under Grant RED2018-102626-T. The work of Elizabeth M. Jefremovas was supported by the Beca Concepción Arenal through the Gobierno de Cantabria-Universidad de Cantabria under Grant BDNS: 406333. The work of Irati Rodrigo was supported by the Programa de Perfeccionamiento de Personal Investigador Doctor (Gobierno Vasco) under Grant POS-2020-1-0028 and Grant IT-1005-16. The work of Lourdes Marcano was supported by the Postdoctoral Fellowship from the Basque Government under Grant POS-2019-2-0017

Loss of supervillin causes myopathy with myofibrillar disorganization and autophagic vacuoles

The muscle specific isoform of the supervillin protein (SV2), encoded by the SVIL gene, is a large sarcolemmal myosin II- and F-actin-binding protein. Supervillin (SV2) binds and co-localizes with costameric dystrophin and binds nebulin, potentially attaching the sarcolemma to myofibrillar Z-lines. Despite its important role in muscle cell physiology suggested by various in vitro studies, there are so far no reports of any human disease caused by SVIL mutations. We here report four patients from two unrelated, consanguineous families with a childhood/adolescence onset of a myopathy associated with homozygous loss-of-function mutations in SVIL. Wide neck, anteverted shoulders and prominent trapezius muscles together with variable contractures were characteristic features. All patients showed increased levels of serum creatine kinase but no or minor muscle weakness. Mild cardiac manifestations were observed. Muscle biopsies showed complete loss of large supervillin isoforms in muscle fibres by western blot and immunohistochemical analyses. Light and electron microscopic investigations revealed a structural myopathy with numerous lobulated muscle fibres and considerable myofibrillar alterations with a coarse and irregular intermyofibrillar network. Autophagic vacuoles, as well as frequent and extensive deposits of lipoproteins, including immature lipofuscin, were observed. Several sarcolemma-associated proteins, including dystrophin and sarcoglycans, were partially mis-localized. The results demonstrate the importance of the supervillin (SV2) protein for the structural integrity of muscle fibres in humans and show that recessive loss-of-function mutations in SVIL cause a distinctive and novel myopathy

Beyond single-mindedness: a figure-ground reversal for the cognitive sciences

A fundamental fact about human minds is that they are never truly alone: all minds are steeped in situated interaction. That social interaction matters is recognized by any experimentalist who seeks to exclude its influence by studying individuals in isolation. On this view, interaction complicates cognition. Here, we explore the more radical stance that interaction co-constitutes cognition: that we benefit from looking beyond single minds toward cognition as a process involving interacting minds. All around the cognitive sciences, there are approaches that put interaction center stage. Their diverse and pluralistic origins may obscure the fact that collectively, they harbor insights and methods that can respecify foundational assumptions and fuel novel interdisciplinary work. What might the cognitive sciences gain from stronger interactional foundations? This represents, we believe, one of the key questions for the future. Writing as a transdisciplinary collective assembled from across the classic cognitive science hexagon and beyond, we highlight the opportunity for a figure-ground reversal that puts interaction at the heart of cognition. The interactive stance is a way of seeing that deserves to be a key part of the conceptual toolkit of cognitive scientists

Beyond Single‐Mindedness: A Figure‐Ground Reversal for the Cognitive Sciences

A fundamental fact about human minds is that they are never truly alone: all minds are steeped in situated interaction. That social interaction matters is recognized by any experimentalist who seeks to exclude its influence by studying individuals in isolation. On this view, interaction complicates cognition. Here, we explore the more radical stance that interaction co-constitutes cognition: that we benefit from looking beyond single minds toward cognition as a process involving interacting minds. All around the cognitive sciences, there are approaches that put interaction center stage. Their diverse and pluralistic origins may obscure the fact that collectively, they harbor insights and methods that can respecify foundational assumptions and fuel novel interdisciplinary work. What might the cognitive sciences gain from stronger interactional foundations? This represents, we believe, one of the key questions for the future. Writing as a transdisciplinary collective assembled from across the classic cognitive science hexagon and beyond, we highlight the opportunity for a figure-ground reversal that puts interaction at the heart of cognition. The interactive stance is a way of seeing that deserves to be a key part of the conceptual toolkit of cognitive scientists

Beyond single-mindedness: A figure-ground reversal for the cognitive sciences

A fundamental fact about human minds is that they are never truly alone: all minds are steeped in situated interaction. That social interaction matters is recognized by any experimentalist who seeks to exclude its influence by studying individuals in isolation. On this view, interaction complicates cognition. Here, we explore the more radical stance that interaction co-constitutes cognition: that we benefit from looking beyond single minds toward cognition as a process involving interacting minds. All around the cognitive sciences, there are approaches that put interaction center stage. Their diverse and pluralistic origins may obscure the fact that collectively, they harbor insights and methods that can respecify foundational assumptions and fuel novel interdisciplinary work. What might the cognitive sciences gain from stronger interactional foundations? This represents, we believe, one of the key questions for the future. Writing as a transdisciplinary collective assembled from across the classic cognitive science hexagon and beyond, we highlight the opportunity for a figure-ground reversal that puts interaction at the heart of cognition. The interactive stance is a way of seeing that deserves to be a key part of the conceptual toolkit of cognitive scientists

'“Who is Kailyal, what is she?” Subcontinental and Metropolitan Reader Responses to The Curse of Kehama and its Heroine'

This article attempts to consider the responses of readers both in the metropole and within the subcontinent to a poem of which Jane Welsh Carlyle wrote: “I should like well to have conceived ‘The curse of Kehama’ – But I would not have written it for a thousand guineas.” Opening with an Elephanta picnic, it examines a wide array of critical and scholarly reactions which testify to the imaginative power and accuracy of Southey's poetic representation of Hindostan. Its detailed attention to “costume” led many, including seasoned India hands, to measure or recall their subcontinental experiences by the light of Southey's epic, which convinced some of its most informed readers that he had actually made the passage to India. It focuses upon reactions to the physical and moral attractions of the poem's heroine Kailyal, a character whom the young Percy Shelley thought “divine”, rendering Kehama “my most favourite poem.” The inspiration for Kailyal is viewed not only in the obvious subcontinental shapes of Śrī Lakshmī and Śakuntalā, but also in terms of Biblical Orientalism and the influence of Klopstock's Messiah. The significance of “Cidli” in both Klopstock's epic and Klopstock's life, as the name he chose to give his beloved avant la lettre epipsyche Margaretha, is considered in respect to the influence upon Southey of their love conceived as predestined and indivisible through all time