Effect of a loss of the mda5/ifih1 gene on the antiviral resistance in a Chinook salmon Oncorhynchus tshawytscha cell line.

Cells are equipped with intracellular RIG-like Receptors (RLRs) detecting double stranded (ds)RNA, a molecule with Pathogen-Associated Molecular Pattern (PAMPs) generated during the life cycle of many viruses. Melanoma Differentiation-Associated protein 5 (MDA5), a helicase enzyme member of the RLRs encoded by the ifih1 gene, binds to long dsRNA molecules during a viral infection and initiates production of type I interferon (IFN1) which orchestrates the antiviral response. In order to understand the contribution of MDA5 to viral resistance in fish cells, we have isolated a clonal Chinook salmon Oncorhynchus tshawytscha epithelial-like cell line invalidated for the ifih1 gene by CRISPR/Cas9 genome editing.

Routine Infectious Diseases Consultations on a Pediatric Cardiac Unit to Improve Positive Blood Culture Management.

Bacteremia can be life-threatening, and highly medicalized patients, such as those with complex congenital heart disease, are at high risk. Infectious diseases (ID) consultation is associated with improved outcomes in bacteremia. We noted an opportunity for improvement in management of positive blood cultures in our cardiac care unit (CCU).

The experiences of pregnancy and NHS maternity care for women who have been trafficked: A qualitative study.

Problem: Little is known about the maternity experiences of women who have been trafficked and further investigation is needed to better inform midwifery practice and to ensure that the voices of women are heard when developing guidance.

Background: People who have been trafficked experience a range of health problems that could impact on pregnancy.

Aim: The aim of this study was to explore the experiences of pregnancy and NHS maternity care for women who have been trafficked, as well as increasing understanding of social and health factors that may impact on pregnancy outcomes.

Peripheral Nerve Crush in Larvae.

The long length of axons makes them vulnerable to damage; hence, it is logical that nervous systems have evolved adaptive mechanisms for responding to axon damage. Studies in have identified evolutionarily conserved molecular pathways that enable axonal degeneration and regeneration of damaged axons and/or dendrites. This protocol describes a simple method for inducing nerve crush injury to motoneuron and sensory neuron axons in the peripheral (segmental) nerves in second- or early third-instar larvae.

Study of Axonal Injury and Degeneration in .

A fundamental feature of nervous systems is a highly specified synaptic connectivity between cells and the ability to adaptively change this connectivity through plasticity mechanisms. Plasticity mechanisms are highly relevant for responding to nervous system damage, and studies using nervous system injury paradigms in (as well as other model organisms) have revealed conserved molecular pathways that are triggered by axon damage. Simple assays that introduce injuries to axons in either adult flies or larvae have proven to be particularly powerful for uncovering mechanisms of axonal degeneration and clearance.

Immobilizing Second-Instar Larvae for Imaging and Surgery Using the Larva Chip.

The simple body plan and semitranslucent cuticle of the larva allow for imaging of structures close to the body wall within intact animals. These include sensory neurons, muscles, neuromuscular junctions, and some regions of the segmental nerve. However, imaging within an intact larva requires a strategy to immobilize the animal in a position that presents the structures within the working distance of the microscope objective.

Laser Microsurgery in Larvae Using the MicroPoint Ablation System.

Laser microsurgery is a robust method to ablate specific cells in the nervous system and probe the functional consequences of their loss in the animal. By introducing focal lesions to small locations in the animal, laser microsurgery also enables disruptions of specific connections within neuronal circuits and the study of how the nervous system responds to precise forms of damage (for instance, damage to specific axons or dendrites, which have been found to evoke different kinds of responses in neurons). The MicroPoint laser is a pulsed dye laser that can be mounted onto any standard microscope, hence is an affordable alternative to two-photon lasers for providing high powered focal ablations.

Wallerian Degeneration and Clearance of Olfactory Receptor Neuron Axons following Antennal Transection.

Neurons extend their axons and dendrites over long distances and rely on evolutionarily conserved mechanisms to maintain the cellular structure and function of neurites at a distance from their cell body. Neurites that lose connection with their cell body following damage or stressors to their cytoskeleton undergo a programmed self-destruction process akin to apoptosis but using different cellular machinery, termed Wallerian degeneration. While first described for vertebrate axons by Augustus Waller in 1850, key discoveries of the enzymes that regulate Wallerian degeneration were made through forward genetic screens in Powerful techniques for genetic manipulation and visualization of single neurons combined with simple methods for introducing axotomy (neuron severing) to certain neuron types in have enabled the discovery and study of the cellular machinery responsible for Wallerian degeneration, in addition to mechanisms that enable clearance of the resulting debris.

Sarm1 is not necessary for activation of neuron-intrinsic growth programs yet required for the Schwann cell repair response and peripheral nerve regeneration.

Upon peripheral nervous system (PNS) injury, severed axons undergo rapid SARM1-dependent Wallerian degeneration (WD). In mammals, the role of SARM1 in PNS regeneration, however, is unknown. Here we demonstrate that is not required for axotomy induced activation of neuron-intrinsic growth programs and axonal growth into a nerve crush site.

DLK signaling in axotomized neurons triggers complement activation and loss of upstream synapses.

Axotomized spinal motoneurons (MNs) lose presynaptic inputs following peripheral nerve injury; however, the cellular mechanisms that lead to this form of synapse loss are currently unknown. Here, we delineate a critical role for neuronal kinase dual leucine zipper kinase (DLK)/MAP3K12, which becomes activated in axotomized neurons. Studies with conditional knockout mice indicate that DLK signaling activation in injured MNs triggers the induction of phagocytic microglia and synapse loss.

Opposing roles of Fos, Raw, and SARM1 in the regulation of axonal degeneration and synaptic structure.

Introduction: The degeneration of injured axons is driven by conserved molecules, including the sterile armadillo TIR domain-containing protein SARM1, the cJun N-terminal kinase JNK, and regulators of these proteins. These molecules are also implicated in the regulation of synapse development though the mechanistic relationship of their functions in degeneration vs. development is poorly understood.

Sustainable production and pharmaceutical applications of β-glucan from microbial sources.

β-glucans are a large class of complex polysaccharides found in abundant sources. Our dietary sources of β-glucans are cereals that include oats and barley, and non-cereal sources can consist of mushrooms, microalgae, bacteria, and seaweeds. There is substantial clinical interest in β-glucans; as they can be used for a variety of diseases including cancer and cardiovascular conditions.

Optimising management of complex regional pain syndrome to improve clinical outcomes throughout the therapy care pathway in England: Protocol for a qualitative interview and observational study with patients and clinicians.

Introduction: Complex Regional Pain Syndrome (CRPS) is a disabling and distressing chronic pain condition characterised by a range of sensory, motor, autonomic and trophic symptoms. Guidelines recommend early referral for therapies that promote movement of the painful limb. However, evidence suggests a lack of defined therapy pathways for CRPS.

'Are Routine Post-discharge Diuretics Necessary After Pediatric Cardiac Surgery?'.

A prospective, one-armed, safety non-inferiority trial with historical controls was performed at a single-center, quaternary, children's hospital. Inclusion criteria were children aged 3 months-18 years after pediatric cardiac surgery resulting in a two-ventricle repair between 7/2020 and 7/2021. Eligible patients were compared with patients from a 5-year historical period (selected using a database search).

Multifaceted roles of SARM1 in axon degeneration and signaling.

Axons are considered to be particularly vulnerable components of the nervous system; impairments to a neuron's axon leads to an effective silencing of a neuron's ability to communicate with other cells. Nervous systems have therefore evolved plasticity mechanisms for adapting to axonal damage. These include acute mechanisms that promote the degeneration and clearance of damaged axons and, in some cases, the initiation of new axonal growth and synapse formation to rebuild lost connections.

Current issues and recommendations to manage prescription drug benefits for public health programs.

Higher scrutiny is befalling public payors regarding drug costs and patient access to medications. These issues exist in a complex contractual environment where minimal oversight of pharmacy claim adjudication and reimbursement practices can occur. The complexity of prescription benefits, and the lack of defined expectations or accountability in the system contribute to a sense of frustration by the public.

Mitochondrial fission, integrity and completion of mitophagy require separable functions of Vps13D in Drosophila neurons.

A healthy population of mitochondria, maintained by proper fission, fusion, and degradation, is critical for the long-term survival and function of neurons. Here, our discovery of mitophagy intermediates in fission-impaired Drosophila neurons brings new perspective into the relationship between mitochondrial fission and mitophagy. Neurons lacking either the ataxia disease gene Vps13D or the dynamin related protein Drp1 contain enlarged mitochondria that are engaged with autophagy machinery and also lack matrix components.

Abnormal Microarray, Clinical Outcomes, and Surgical Risk Scores in Young Children with Cardiac Disease.

The clinical implications of abnormal chromosomal microarray (CMA) remain unclear for children less than 1 year of age with critical heart disease. Our objective was to determine whether abnormal CMA was related to surgical severity scores or to pre-determined clinical outcomes, including cardiac arrest. Retrospective review of children under 1 year of age admitted to a pediatric cardiac intensive care unit from December, 2014 to September, 2017.

Regulation of longevity by depolarization-induced activation of PLC-β-IPR signaling in neurons.

Mitochondrial ATP production is a well-known regulator of neuronal excitability. The reciprocal influence of plasma-membrane potential on ATP production, however, remains poorly understood. Here, we describe a mechanism by which depolarized neurons elevate the somatic ATP/ADP ratio in glutamatergic neurons.

An NAD+/NMN balancing act by SARM1 and NMNAT2 controls axonal degeneration.

Axonal degeneration is controlled by the TIR domain NADase SARM1. In this issue of Neuron, Figley et al. (2021) reveal a key regulatory mechanism that controls SARM1's enzymatic activity, providing insight into how NAD+ biosynthesis by the NMNAT2 enzyme protects axons, and a new therapeutic path to tune SARM1 activity.

Non-Lethal Sequential Individual Monitoring of Viremia in Relation to DNA Vaccination in Fish-Example Using a Salmon Alphavirus DNA Vaccine in Atlantic Salmon .

Traditionally, commercial testing for vaccine efficacy has relied on the mass infection of vaccinated and unvaccinated animals and the comparison of mortality prevalence and incidence. For some infection models where disease does not cause mortality this approach to testing vaccine efficacy is not useful. Additionally, in fish experimental studies on vaccine efficacy and immune response the norm is that several individuals are lethally sampled at sequential timepoints, and results are extrapolated to represent the kinetics of immune and disease parameters of an individual fish over the entire experimental infection period.

Stac protein regulates release of neuropeptides.

Neuropeptides are important for regulating numerous neural functions and behaviors. Release of neuropeptides requires long-lasting, high levels of cytosolic Ca However, the molecular regulation of neuropeptide release remains to be clarified. Recently, Stac3 was identified as a key regulator of L-type Ca channels (CaChs) and excitation-contraction coupling in vertebrate skeletal muscles.