, the Gene Mutated in Familial Dysautonomia, Is Required for Normal Enteric Nervous System Development and Maintenance and for Gut Epithelium Homeostasis.

Familial dysautonomia (FD) is a rare sensory and autonomic neuropathy that results from a mutation in the gene. Virtually all patients report gastrointestinal (GI) dysfunction and we have recently shown that FD patients have a dysbiotic gut microbiome and altered metabolome. These findings were recapitulated in an FD mouse model and moreover, the FD mice had reduced intestinal motility, as did patients.

Titin is a nucleolar protein in neurons.

Titin is the largest protein produced by living cells and its function as a molecular spring in striated muscle is well characterized (1, 2). Here we demonstrate that titin isoforms in the same size range as found in muscle are prominent neuronal proteins in both the central and peripheral nervous systems, including motor neurons in the spinal cord and brain. Within these neurons, titin localizes to the dense fibrillar component of the nucleolus, the site of ribosomal RNA biogenesis and modification, and a critical site of dysfunction in neurodegenerative disease (3-5).

Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators.

Familial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 (ELP1) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently patient symptoms are managed, but there is no treatment for the disease.

Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators.

Familial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 ( ) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently, patient symptoms are managed, but there is no treatment for the disease.

Elongator regulates the melanocortin satiety pathway.

This study investigates the function of Elp1 and Elongator in the pituitary gland. Two conditional knockout models were generated where Elp1 was selectively deleted in either somatotropes of the anterior pituitary or Pomc-expressing cells of the anterior and intermediate pituitary. Although loss of Elp1 in somatotropes did not significantly impact murine growth or development, its loss in Pomc-expressing cells resulted in dramatically reduced levels of α-MSH, hyperphagia and obesity.

Elp1 is required for development of visceral sensory peripheral and central circuitry.

Cardiovascular instability and a blunted respiratory drive in hypoxic conditions are hallmark features of the genetic sensory and autonomic neuropathy, familial dysautonomia (FD). FD results from a mutation in the gene ELP1, the encoded protein of which is a scaffolding subunit of the six-subunit Elongator complex. In mice, we and others have shown that Elp1 is essential for the normal development of neural crest-derived dorsal root ganglia sensory neurons.

Loss of Elp1 perturbs histone H2A.Z and the Notch signaling pathway.

Elongator dysfunction is increasingly recognized as a contributor to multiple neurodevelopmental and neurodegenerative disorders including familial dysautonomia, intellectual disability, amyotrophic lateral sclerosis, and autism spectrum disorder. Although numerous cellular processes are perturbed in the context of Elongator loss, converging evidence from multiple studies has resolved Elongator's primary function in the cell to the modification of tRNA wobble uridines and the translational regulation of codon-biased genes. Here we characterize H2a.

Supporting the Quality of Measurement and Evaluation in Education.

The impetus for the development of a measurement and evaluation team for Robert Morris University, School of Nursing and Health Sciences (SNHS), was to foster faculty and administration commitment in enhancing the quality of measurement and evaluation processes. Many of the SNHS faculty members had experienced incidents of academic inconsistencies with student exam protocols. The measurement and evaluation team was charged to define the goals for faculty to use evidence-based assessment and evaluation strategies that are appropriate for the learner and learning goals, support use of evaluation data to measure the achievement of designated outcomes, and promote curricular excellence through the use of assessment and evaluation data and policies to enhance the teaching and learning process.

Elongator and codon bias regulate protein levels in mammalian peripheral neurons.

Familial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for the Elongator complex. This highly conserved complex is required for the translation of codon-biased genes in lower organisms. Here we investigate whether Elongator serves a similar function in mammalian peripheral neurons, the population devastated in FD.

Animal and cellular models of familial dysautonomia.

Since Riley and Day first described the clinical phenotype of patients with familial dysautonomia (FD) over 60 years ago, the field has made considerable progress clinically, scientifically, and translationally in treating and understanding the etiology of FD. FD is classified as a hereditary sensory and autonomic neuropathy (HSAN type III) and is both a developmental and a progressive neurodegenerative condition that results from an autosomal recessive mutation in the gene IKBKAP, also known as ELP1. FD primarily impacts the peripheral nervous system but also manifests in central nervous system disruption, especially in the retina and optic nerve.

Effect of the dedicated education unit on nursing student self-efficacy: A quasi-experimental research study.

Although the Dedicated Education Unit (DEU) has shown initial promise related to satisfaction with the teaching/learning environment, few studies have examined student outcomes related to the use of the DEU as a clinical education model beyond student satisfaction. The purpose of this quantitative, quasi-experimental study was to compare student outcomes from the traditional clinical education (TCE) model with those from the DEU model. Participants were students enrolled in a four-year baccalaureate program in nursing (n = 193) who had clinical education activities in one of three clinical agencies.

The familial dysautonomia disease gene is required in the developing and adult mouse central nervous system.

Hereditary sensory and autonomic neuropathies (HSANs) are a genetically and clinically diverse group of disorders defined by peripheral nervous system (PNS) dysfunction. HSAN type III, known as familial dysautonomia (FD), results from a single base mutation in the gene that encodes a scaffolding unit (ELP1) for a multi-subunit complex known as Elongator. Since mutations in other Elongator subunits (ELP2 to ELP4) are associated with central nervous system (CNS) disorders, the goal of this study was to investigate a potential requirement for in the CNS of mice The sensory and autonomic pathophysiology of FD is fatal, with the majority of patients dying by age 40.

Preparing New Nurses to Address Bullying: The Effect of an Online Educational Module on Learner Self-Efficacy.

Newly licensed nurses who start their careers in supportive, nurtur- ing environments are more likely to overcome challenges and successfully transition into professional practice (Spiva et al., 2013). Introduction of content about bullying in the workplace via an online educational module can be an effective strategy for the academic preparation of pre-licensure nursing students.

In vivo time-lapse imaging reveals extensive neural crest and endothelial cell interactions during neural crest migration and formation of the dorsal root and sympathetic ganglia.

During amniote embryogenesis the nervous and vascular systems interact in a process that significantly affects the respective morphogenesis of each network by forming a "neurovascular" link. The importance of neurovascular cross-talk in the central nervous system has recently come into focus with the growing awareness that these two systems interact extensively both during development, in the stem-cell niche, and in neurodegenerative conditions such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis. With respect to the peripheral nervous system, however, there have been no live, real-time investigations of the potential relationship between these two developing systems.

Neuroblastoma tyrosine kinase signaling networks involve FYN and LYN in endosomes and lipid rafts.

Protein phosphorylation plays a central role in creating a highly dynamic network of interacting proteins that reads and responds to signals from growth factors in the cellular microenvironment. Cells of the neural crest employ multiple signaling mechanisms to control migration and differentiation during development. It is known that defects in these mechanisms cause neuroblastoma, but how multiple signaling pathways interact to govern cell behavior is unknown.

Osteomyelitis: an overview of imaging modalities.

Diagnosis, early intervention, and treatment of patients who have an infection are the basic foundations of patient care. Early, appropriate interventions are associated with decreased patient morbidity and mortality. Diagnostic procedures with clinical information and laboratory results are integral in the assessment of inflammatory diseases and the prevention of sepsis.

Familial dysautonomia model reveals Ikbkap deletion causes apoptosis of Pax3+ progenitors and peripheral neurons.

Familial dysautonomia (FD) is a devastating developmental and progressive peripheral neuropathy caused by a mutation in the gene inhibitor of kappa B kinase complex-associated protein (IKBKAP). To identify the cellular and molecular mechanisms that cause FD, we generated mice in which Ikbkap expression is ablated in the peripheral nervous system and identify the steps in peripheral nervous system development that are Ikbkap-dependent. We show that Ikbkap is not required for trunk neural crest migration or pathfinding, nor for the formation of dorsal root or sympathetic ganglia, or the adrenal medulla.

IKAP/Elp1 is required in vivo for neurogenesis and neuronal survival, but not for neural crest migration.

Familial Dysautonomia (FD; Hereditary Sensory Autonomic Neuropathy; HSAN III) manifests from a failure in development of the peripheral sensory and autonomic nervous systems. The disease results from a point mutation in the IKBKAP gene, which encodes the IKAP protein, whose function is still unresolved in the developing nervous system. Since the neurons most severely depleted in the disease derive from the neural crest, and in light of data identifying a role for IKAP in cell motility and migration, it has been suggested that FD results from a disruption in neural crest migration.

Preliminary exploration of the use of a medical malpractice self-study module.

This study was conducted to determine the effectiveness of an educational module on medical malpractice litigation and the use of evidence-based practice guidelines. Data regarding knowledge acquisition, ease of use, and the perceived value of the educational module were collected. A pretest-posttest design was used.

Technology in nursing education: a study of PDA use by students.

Personal digital assistants (PDAs) were first used by the public in the early 1990 s. Initially used as a device to manage personal information, these devices quickly evolved. Currently, PDAs are capable of storing and exchanging large amounts of information, which truly make them handheld computers.

Patterned assembly and neurogenesis in the chick dorsal root ganglion.

The birth of small-diameter TrkA+ neurons that mediate pain and thermoreception begins approximately 24 hours after the cessation of neural crest cell migration from progenitors residing in the nascent dorsal root ganglion. Although multiple geographically distinct progenitor pools have been proposed, this study is the first to comprehensively characterize the derivation of small-diameter neurons. In the developing chick embryo we identify novel patterns in neural crest cell migration and colonization that sculpt the incipient ganglion into a postmitotic neuronal core encapsulated by a layer of proliferative progenitor cells.

The ACA10 Ca2+-ATPase regulates adult vegetative development and inflorescence architecture in Arabidopsis.

The Arabidopsis (Arabidopsis thaliana) compact inflorescence (cif) genotype causes altered adult vegetative development and a reduction in elongation of inflorescence internodes resulting in formation of floral clusters. The cif trait requires both a recessive mutation, cif1, and the activity of a naturally occurring dominant allele of an unlinked gene, CIF2(D). We show here that the pseudoverticillata mutation is allelic with cif1 and that the product of the CIF1 gene is ACA10, a member of the large family of P-type Ca(2+)-ATPases found in higher plants.