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

Historical dataset details the distribution, extent and form of lost Ostrea edulis reef ecosystems

Ocean ecosystems have been subjected to anthropogenic influences for centuries, but the scale of past ecosystem changes is often unknown. For centuries, the European flat oyster (Ostrea edulis), an ecosystem engineer providing biogenic reef habitats, was a culturally and economically significant source of food and trade. These reef habitats are now functionally extinct, and almost no memory of where this ecosystem once existed, at what scales, or its past form and functioning, remains. The described datasets present qualitative and quantitative extracts from written records published between 1524 and 2022, which show: (1) locations of past oyster fisheries and/or oyster reef habitat across its biogeographical range, with associated levels of confidence; (2) extent of past oyster reef habitats, and; (3) species associated with these habitats. These datasets will be of use to inform accelerating restoration activities, to establish reference models for anchoring adaptive management of restoration action, and in contributing to global efforts to recover records on the hidden history of anthropogenic-driven ocean ecosystem degradation

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

The world was our oyster:Records reveal the vast historical extent of European oyster reef ecosystems

Anthropogenic activities have impacted marine ecosystems at extraordinary scales. Biogenic reef ecosystems built by the European flat oyster (Ostrea edulis) typically declined prior to scientific monitoring. Collating >1,600 records published over 350 years, we created a highly resolved (10km2) map of historical oyster reef presence across its biogeographic range, including documenting abundant reef habitats along the coasts of France, Denmark, Ireland and the United Kingdom. Areal extent data were available from just 26% of locations, yet totalled >1.7 million hectares (median reef size = 30ha, range 0.01 - 1,536,000ha), with 190 associated macrofauna species from 13 phyla described. Our analysis demonstrates that oyster reefs were once a dominant three-dimensional feature of European coastlines, with their loss pointing to a fundamental restructuring and ‘flattening’ of coastal and shallow-shelf seafloors. This unique empirical record demonstrates the highly degraded nature of European seas and provides key baseline context for international restoration commitments