Ultrastructural Analysis Reveals Mitochondrial Placement Independent of Synapse Placement in Fine Caliber C. elegans Neurons.

Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of metabolite diffusion over long distances, it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity such as synapses.

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons.

Extracellular vesicles (EVs) are submicron membranous structures and key mediators of intercellular communication. Recent research has highlighted roles for cilia-derived EVs in signal transduction, underscoring their importance as bioactive extracellular organelles containing conserved ciliary signaling proteins. Members of the transient receptor potential (TRP) channel polycystin-2 (PKD-2) family are found in ciliary EVs of the green algae Chlamydomonas and the nematode Caenorhabditis elegans and in EVs in the mouse embryonic node and isolated from human urine.

NEKL-4 regulates microtubule stability and mitochondrial health in ciliated neurons.

Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant in cilia, and its dysregulation may contribute to ciliopathies and neurodegeneration. Mutation of the deglutamylase CCP1 causes infantile-onset neurodegeneration.

Expression of , , and in the mature cochlea reprograms nonsensory cells into hair cells.

Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate; consequently, loss of hair cells leads to permanent hearing loss. Although nonmammalian vertebrates can regenerate hair cells from neighboring supporting cells, many humans with severe hearing loss lack both hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of nonsensory cells. To determine whether the mature cochlea can produce hair cells in vivo, we reprogrammed nonsensory cells adjacent to the organ of Corti with three hair cell transcription factors: , , and We generated numerous hair cell-like cells in nonsensory regions of the cochlea and new hair cells continued to be added over a period of 9 wk.

A novel pulsed field ablation system using linear and spiral ablation catheters can create large and durable endocardial and epicardial ventricular lesions in vivo.

Background: We investigated the preclinical safety and efficacy of ventricular pulsed field ablation (PFA) using a family of novel, 6-/8-Fr, linear, and spiral PFA/mapping catheters (CRC EP, Inc).

Methods: QRS-gated, bipolar PFA (>2.0 kV) was performed in 10 healthy swine.

Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons.

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressed touch neurons, are poorly understood. Here we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons.

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons.

Cilia-derived extracellular vesicles (EVs) contain signaling proteins and act in intercellular communication. Polycystin-2 (PKD-2), a transient receptor potential channel, is a conserved ciliary EVs cargo. serves as a model for studying ciliary EV biogenesis and function.

PGP-14 establishes a polar lipid permeability barrier within the C. elegans pharyngeal cuticle.

The cuticles of ecdysozoan animals are barriers to material loss and xenobiotic insult. Key to this barrier is lipid content, the establishment of which is poorly understood. Here, we show that the p-glycoprotein PGP-14 functions coincidently with the sphingomyelin synthase SMS-5 to establish a polar lipid barrier within the pharyngeal cuticle of the nematode C.

Patient-Level Characteristics Associated with Tobacco Users and Nonusers at a Student-Run Free Clinic.

Objectives: Many tobacco users are motivated to quit but lack the resources to do so. To date, studies characterizing tobacco users at student-run free clinics have used small sample sizes, which may not be large enough to detect differences across key variables. As such, we assessed sociodemographic differences between tobacco users and nonusers at a student-run free clinic using a pooled cross-sectional design.

Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers.

Toxic protein aggregates can spread among neurons to promote human neurodegenerative disease pathology. We found that in C. elegans touch neurons intermediate filament proteins IFD-1 and IFD-2 associate with aggresome-like organelles and are required cell-autonomously for efficient production of neuronal exophers, giant vesicles that can carry aggregates away from the neuron of origin.

Preclinical evaluation of a novel single-shot pulsed field ablation system for pulmonary vein and atrial ablation.

Introduction: Pulsed field ablation (PFA) is a nonthermal ablative strategy that achieves cell death via electroporation. Herein, we investigated the preclinical safety and efficacy of PFA using two novel 8-French, 16-electrode spiral PFA/mapping catheters (ElePulse; CRC EP, Inc.).

Ultrastructural analysis reveals mitochondrial placement independent of synapse placement in fine caliber C. elegans neurons.

Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion over long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses.

Large vesicle extrusions from neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell.

neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron.

Innexin function dictates the spatial relationship between distal somatic cells in the gonad without impacting the germline stem cell pool.

Gap-junctional signaling mediates myriad cellular interactions in metazoans. Yet, how gap junctions control the positioning of cells in organs is not well understood. Innexins compose gap junctions in invertebrates and affect organ architecture.

A transient apical extracellular matrix relays cytoskeletal patterns to shape permanent acellular ridges on the surface of adult C. elegans.

Epithelial cells secrete apical extracellular matrices to form protruding structures such as denticles, ridges, scales, or teeth. The mechanisms that shape these structures remain poorly understood. Here, we show how the actin cytoskeleton and a provisional matrix work together to sculpt acellular longitudinal alae ridges in the cuticle of adult C.

Correction: Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.

[This corrects the article DOI: 10.1371/journal.pgen.

Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.

The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons.

LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors.

Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB1) and SKAP55 (SKAP1) are recruited into microclusters and activate integrins via the effectors talin-1 and kindlin-3 (FERMT3). We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages.

The initial expansion of the C. elegans syncytial germ line is coupled to incomplete primordial germ cell cytokinesis.

The C. elegans germline is organized as a syncytium in which each germ cell possesses an intercellular bridge that is maintained by a stable actomyosin ring and connected to a common pool of cytoplasm, termed the rachis. How germ cells undergo cytokinesis while maintaining this syncytial architecture is not completely understood.

The Prop1-like homeobox gene specifies the identity of synaptically connected neurons.

Many neuronal identity regulators are expressed in distinct populations of cells in the nervous system, but their function is often analyzed only in specific isolated cellular contexts, thereby potentially leaving overarching themes in gene function undiscovered. We show here that the Prop1-like homeobox gene is expressed in 15 distinct sensory, inter- and motor neuron classes throughout the entire nervous system. Strikingly, all 15 neuron classes expressing are synaptically interconnected, prompting us to investigate whether controls the functional properties of this circuit and perhaps also the assembly of these neurons into functional circuitry.