The next phase of biomolecular condensate research.

The Cell Reports team recently attended the Keystone Symposia on Biological Condensates. The meeting was a great opportunity to learn about the latest developments in this exciting area. In this Voices piece, we asked three researchers in the field how the landscape of biomolecular condensate research is evolving.

Assessing the Use of Recommended Practices in Adapted Physical Activity/Education Experiential-Learning Programs.

This study investigated the use of recommended practices in university-based experiential learning associated with adapted physical activity and education (APA/E) undergraduate courses. Participants (N = 165) were instructors of APA/E courses with an experiential-learning component and/or professionals involved in APA/E experiential-learning programs at their university. Participants completed an online questionnaire designed to describe program characteristics and evaluate the use of two sets of practices, including those recommended for involving students and people with disabilities.

Subcutaneous Oxytocin Injection Reduces Heat Pain: A Randomized-Controlled Trial.

Oxytocin (OT) is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local.

Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research.

Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research.

Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa.

Pompe disease is an inherited, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase and accumulation of glycogen in tissues, resulting in cellular dysfunction, muscle damage, and functional disabilities. Enzyme replacement therapy with alglucosidase alfa (Myozyme/Lumizyme) has led to better outcomes, but many patients have plateaued or declined despite treatment. The second-generation ERT avalglucosidase alfa (Nexviazyme) was designed to have enhanced cellular uptake via the conjugation of additional bis-mannose-6-phosphate residues.

Effect of castration timing and weaning strategy on the taxonomic and functional profile of ruminal bacteria and archaea of beef calves.

Background: Beef cattle experience several management challenges across their lifecycle. Castration and weaning, two major interventions in the early life of beef cattle, can have a substantial impact on animal performance. Despite the key role of the rumen microbiome on productive traits of beef cattle, the effect of castration timing and weaning strategy on this microbial community has not been formally described.

Phase separation in chemical and mechanical signal transduction.

Signal transduction enables cells to sense and respond to chemical and mechanical information in the extracellular environment. Recently, phase separation has emerged as a physical mechanism that can influence the spatial organization of signaling molecules and regulate downstream signaling. Although many molecular components of signaling pathways, including receptors, kinases, and transcription factors, have been observed to undergo phase separation, understanding the functional consequences of their phase separation in signal transduction remains an ongoing area of research.

Screening data from 19 patients with late-onset Pompe disease for a phase I clinical trial of AAV8 vector-mediated gene therapy.

Late-onset Pompe disease (LOPD) is a multisystem disorder with significant myopathy. The standard treatment is enzyme replacement therapy (ERT), a therapy that is lifesaving, yet with limitations. Clinical trials have emerged for other potential treatment options, including adeno-associated virus (AAV) gene therapy.

Muscle ultrasound in patients with late-onset Pompe disease identified by newborn screening.

Importance: Implementation of newborn screening (NBS) in the United States now detects infants with late-onset Pompe disease (LOPD), a lysosomal storage disease characterized by slowly progressive muscle weakness, and detailed clinical evaluation has identified early muscle weakness. Biomarkers may be uninformative; thus, non-invasive imaging is needed to assess early LOPD muscle changes. Muscle ultrasound (US) measuring echointensity (EI) is a non-invasive measure of muscle health.

Corrigendum: Reconstitution of phase-separated signaling clusters and actin polymerization on supported lipid bilayers.

[This corrects the article DOI: 10.3389/fcell.2022.

Aβ-CT Affective Touch: Touch Pleasantness Ratings for Gentle Stroking and Deep Pressure Exhibit Dependence on A-Fibers.

Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway.

Chronic pain patients low in social connectedness report higher pain and need deeper pressure for pain relief.

The experience of rejection and disconnection reliably amplifies pain. Yet, little is known about the impact of enduring feelings of closeness, or social connectedness, on experiences of chronic pain. The current secondary analysis tested the hypothesis that greater social connectedness would predict lower chronic pain ratings, mediated by lower depression and anxiety.

A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization.

Histamine plays pivotal role in normal physiology and dysregulated production of histamine or signaling through histamine receptors (HRH) can promote pathology. Previously, we showed that Bordetella pertussis or pertussis toxin can induce histamine sensitization in laboratory inbred mice and is genetically controlled by Hrh1/HRH1. HRH1 allotypes differ at three amino acid residues with P-V-L and L-M-S, imparting sensitization and resistance respectively.

Phase I study of liver depot gene therapy in late-onset Pompe disease.

Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy (ERT) by creating a liver depot for acid α-glucosidase (GAA) production. We report initial safety and bioactivity of the first dose (1.6 × 10 vector genomes/kg) cohort (n = 3) in a 52-week open-label, single-dose, dose-escalation study (NCT03533673) in patients with late-onset Pompe disease (LOPD).

Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood.

How cells sense and integrate information from different sources.

Cell signaling is a fundamental cellular process that enables cells to sense and respond to information in their surroundings. At the molecular level, signaling is primarily carried out by transmembrane protein receptors that can initiate complex downstream signal transduction cascades to alter cellular behavior. In the human body, different cells can be exposed to a wide variety of environmental conditions, and cells express diverse classes of receptors capable of sensing and integrating different signals.

Tuning conformational asymmetry in particle-forming diblock copolymer alloys.

Self-consistent field theory is employed to compute the phase behavior of binary blends of conformationally asymmetric, micelle-forming diblock copolymers with miscible corona blocks and immiscible core blocks (a diblock copolymer "alloy"). The calculations focus on establishing conditions that promote the formation of Laves phases by tuning the relative softness of the cores of the two different Laves phase particles independent control of their conformational asymmetries. Increasing the conformational asymmetry of the more spherical particles of the Laves structure has a stabilizing effect, consistent with the expectations of increased imprinting of the Wigner-Seitz cells on the core/corona interface as conformational asymmetry increases.

Guidelines for treating child and adolescent obesity: A systematic review.

Obesity is a chronic disease that compromises the physical and mental health of an increasing proportion of children globally. In high-income countries, prevalence of paediatric obesity is increasing faster in those from marginalised populations such as low-income households, suggesting the disease as one that is largely systemic. Appropriate treatment should be prioritised in these settings to prevent the development of complications and co-morbidities and manage those that already exist.

Reconstitution of Phase-Separated Signaling Clusters and Actin Polymerization on Supported Lipid Bilayers.

Liquid-liquid phase separation driven by weak interactions between multivalent molecules contributes to the cellular organization by promoting the formation of biomolecular condensates. At membranes, phase separation can promote the assembly of transmembrane proteins with their cytoplasmic binding partners into micron-sized membrane-associated condensates. For example, phase separation promotes clustering of nephrin, a transmembrane adhesion molecule, resulting in increased Arp2/3 complex-dependent actin polymerization.

Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial.

Aim: To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP).

Method: Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 10 AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 × 10 hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 × 10 AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition.

Evaluating 12 Years of Implementing a Multidisciplinary Specialist Child and Adolescent Obesity Treatment Service: Patient-Level Outcomes.

Introduction: Childhood obesity is a chronic disease that requires multidisciplinary and specialist intervention to address its complex pathophysiology, though access to treatment is limited globally. Evaluating the impact of evidence-based interventions implemented in real-world clinical settings is essential, in order to increase the translation of research into practice and enhance child health outcomes. In Ireland, the National Model of Care for Obesity highlighted the need to develop and improve healthcare services for children and adolescents with obesity.

Early clinical phenotype of late onset Pompe disease: Lessons learned from newborn screening.

Purpose: Thoroughly phenotype children with late-onset Pompe disease (LOPD) diagnosed via newborn screening (NBS) to provide guidance for long-term follow up.

Methods: Twenty infants ages 6-21 months with LOPD diagnosed by NBS underwent systematic clinical evaluation at Duke University including cardiac imaging, biomarker testing, physical therapy evaluation, and speech-language pathology evaluation.

Results: Of the 20 infants, four were homozygous for the "late-onset" IVS1 splice site variant c.