The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.

L-Amino acid transporters (LATs) play a key role in a wide range of physiological processes. Defects in LATs can lead to neurological disorders and aminoacidurias, while the overexpression of these transporters is related to cancer. BasC is a bacterial LAT transporter with an APC fold.

Ganglioside GD2 Contributes to a Stem-Like Phenotype in Intrahepatic Cholangiocarcinoma.

Background & Aims: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

Methods: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON).

Bridging trauma and eating disorders: the role of loneliness.

Introduction: Eating disorders (EDs) are complex and often linked to traumatic childhood experiences. While childhood trauma is known to increase the risk of EDs, the role of loneliness remains underexplored. This study investigates whether loneliness mediates the relationship between childhood trauma and ED symptoms.

CD3+CD4-CD8- Double-Negative Lymphocytes Are Increased in the Aqueous Humor of Patients with Retinitis Pigmentosa: Their Possible Role in Mediating Inflammation.

Recently, evidence has supported a significant role for immune and oxidative-mediated damage underlying the pathogenesis of different types of retinal diseases, including retinitis pigmentosa (RP). Our study aimed to evaluate the presence of immune cells and mediators in patients with RP using flow cytometric analysis of peripheral blood (PB) and aqueous humor (AH) samples. We recruited 12 patients with RP and nine controls undergoing cataract surgery.

Pimozide and Adipic Acid: A New Multicomponent Crystalline Entity for Improved Pharmaceutical Behavior.

Pimozide is a first-generation antipsychotic used in the treatment of schizophrenia, Gilles de la Tourette syndrome, and other chronic psychoses. Its in vivo efficacy is limited by poor solubility and consequent poor bioavailability. Therefore, adipic acid was used as a coformer for the preparation of a binary product with improved pharmaceutical properties.

Female mice exhibit similar long-term plasticity and microglial properties between the dorsal and ventral hippocampal poles.

The hippocampus is a heterogenous structure that exhibits functional segregation along its longitudinal axis. We recently showed that in male mice, microglia, the brain's resident immune cells, differ between the dorsal (DH) and ventral (VH) hippocampus, impacting long-term potentiation (LTP) mainly through the CX3CL1-CX3CR1 signaling. Here, we assessed the specific features of the hippocampal poles in female mice, demonstrating a similar LTP amplitude in VH and DH in both control and Cx3cr1 knock-out mice.

A Perspective on the Use of Hydroxyapatites to Improve the Dissolution Behavior of Poorly Water-Soluble Piretanide.

Background/objectives: Interest in drug delivery systems (DDS) based on inorganic substrates has increased in parallel with the increase in the number of poorly water-soluble drugs. Hydroxyapatite is one of the ideal matrices for DDS due to its biocompatibility, low cost, and ease of preparation.

Methods: We propose two doped hydroxyapatites, one with Ba on Ca sites another with Si on P sites, with the aim of improving the dissolution rate of piretanide, a diuretic, poorly water-soluble drug.

Initiation of lumen formation from junctions via differential actomyosin contractility regulated by dynamic recruitment of Rasip1.

De novo lumen formation necessitates the precise segregation of junctional proteins from apical surfaces, yet the underlying mechanisms remain unclear. Using a zebrafish model, we develop a series of molecular reporters, photo-convertible and optogenetic tools to study the establishment of apical domains. Our study identifies Rasip1 as one of the earliest apical proteins recruited, which suppresses actomyosin contractility at junctional patches by inhibiting NMII, thereby allowing for the sustained outward flow of junctional complexes.

275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management, 9-11 February 2024, Hoofddorp, the Netherlands.

The 275th ENMC workshop on the diagnosis and management of seronegative myasthenia gravis (SNMG) was held on February 9-11, 2024. The participants included experts in the field of adult and pediatric MG together with patient representatives. This workshop aimed to redefine SNMG in view of recent diagnostic and therapeutic updates and to identify patient unmet needs.

Biological biomarkers in muscle diseases relevant for follow-up and evaluation of treatment.

Muscle diseases cover a diverse group of disorders that in most cases are hereditary. The rarity of the individual muscle diseases provides a challenge for researchers when wanting to establish natural history of the conditions and when trying to develop diagnostic tools, therapies, and outcome measures to evaluate disease progression. With emerging molecular therapies in many genetic muscle diseases, as well as biological therapies for the immune-mediated ones, biological biomarkers play an important role in both drug development and evaluation.

Oscillatory contractile forces refine endothelial cell-cell interactions for continuous lumen formation governed by Heg1/Ccm1.

The formation and organization of complex blood vessel networks rely on various biophysical forces, yet the mechanisms governing endothelial cell-cell interactions under different mechanical inputs are not well understood. Using the dorsal longitudinal anastomotic vessel (DLAV) in zebrafish as a model, we studied the roles of multiple biophysical inputs and cerebral cavernous malformation (CCM)-related genes in angiogenesis. Our research identifies heg1 and krit1 (ccm1) as crucial for the formation of endothelial cell-cell interfaces during anastomosis.

Thrombospondin-4 as potential cerebrospinal fluid biomarker for therapy response in pediatric spinal muscular atrophy.

Background And Purpose: Spinal muscular atrophy (SMA) as the second most common neurodegenerative disorder in childhood is characterized by the deficiency of survival of motor neuron (SMN) protein leading predominantly to degeneration of alpha motor neurons and consequently to progressive muscle weakness and atrophy. Besides some biomarkers like SMN2 copy number therapeutic biomarkers for SMA with known relevance for neuromuscular transmission are lacking. Here, we examined the potential of Thrombospondin-4 (TSP4) to serve as a cerebrospinal fluid (CSF) biomarker, which may also indicate treatment response.

Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis.

Introduction: Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice.

Methods: Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)].

Adult Neurogenesis, Learning and Memory.

Neural plasticity can be defined as the ability of neural circuits to be shaped by external and internal factors. It provides the brain with a capacity for functional and morphological remodelling, with many lines of evidence indicating that these changes are vital for learning and memory formation. The basis of this brain plasticity resides in activity- and experience-driven modifications of synaptic strength, including synaptic formation, elimination or weakening, as well as of modulation of neuronal population, which drive the structural reorganization of neural networks.

Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

Introduction/aims: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity.

Introduction: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated.