Improving Electroencephalography Screening via an Online Module for Neurology Trainees: A Multicenter Study.

Purpose: To investigate the utility of a 15-minute online module to improve the self-confidence and knowledge of neurology trainees when screening an EEG.

Methods: We developed a fast, convenient, and accessible 15-minute online module to teach basic concepts of EEG screening using a five-step approach. To assess the efficacy of the module among neurology trainees, three surveys were developed.

Conformational sampling of CMT-2D associated GlyRS mutations.

During protein synthesis, aminoacyl-tRNA synthetases covalently link amino acids with their cognate tRNAs. Amino acid mutations in glycyl-tRNA synthetase can disrupt protein synthesis and lead to a neurological disorder known as Charcot-Marie-Tooth disease type 2D (CMT-2D). Several studies employing diverse techniques have identified potential disease mechanisms at the molecular level.

HDAC6 Inhibition Corrects Electrophysiological and Axonal Transport Deficits in a Human Stem Cell-Based Model of Charcot-Marie-Tooth Disease (Type 2D).

Charcot-Marie-Tooth disease type 2D (CMT2D), is a hereditary peripheral neuropathy caused by mutations in the gene encoding glycyl-tRNA synthetase (GARS1). Here, human induced pluripotent stem cell (hiPSC)-based models of CMT2D bearing mutations in GARS1 and their use for the identification of predictive biomarkers amenable to therapeutic efficacy screening is described. Cultures containing spinal cord motor neurons generated from this line exhibit network activity marked by significant deficiencies in spontaneous action potential firing and burst fire behavior.

Human Induced Pluripotent Stem Cell-Derived TDP-43 Mutant Neurons Exhibit Consistent Functional Phenotypes Across Multiple Gene Edited Lines Despite Transcriptomic and Splicing Discrepancies.

Gene editing technologies hold great potential to enhance our ability to model inheritable neurodegenerative diseases. Specifically, engineering multiple amyotrophic lateral sclerosis (ALS) mutations into isogenic cell populations facilitates determination of whether different causal mutations cause pathology shared mechanisms, and provides the capacity to separate these mechanisms from genotype-specific effects. As gene-edited, cell-based models of human disease become more commonplace, there is an urgent need to verify that these models constitute consistent and accurate representations of native biology.

Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature.

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria.

Astrocyte-derived extracellular vesicles enhance the survival and electrophysiological function of human cortical neurons in vitro.

Neurons derived from human induced pluripotent stem cells (hiPSCs) are powerful tools for modeling neural pathophysiology and preclinical efficacy/toxicity screening of novel therapeutic compounds. However, human neurons cultured in vitro typically do not fully recapitulate the physiology of the human nervous system, especially in terms of exhibiting morphological maturation, longevity, and electrochemical signaling ability comparable to that of adult human neurons. In this study, we investigated the potential for astrocyte-derived extracellular vesicles (EVs) to modulate survival and electrophysiological function of human neurons in vitro.

Glacier recession alters stream water quality characteristics facilitating bloom formation in the benthic diatom Didymosphenia geminata.

Glaciers provide cold, turbid runoff to many mountain streams in the late summer and buffer against years with low snowfall. The input of glacial meltwater to streams maintains unique habitats and support a diversity of stream flora and fauna. In western Canada, glaciers are anticipated to retreat by 60-80% by the end of the century, and this retreat will invoke widespread changes in mountain ecosystems.

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking.

Recent advances in understanding context-dependent mechanisms controlling neurotrophin signaling and function.

Complex mechanisms control the signaling of neurotrophins through p75 and Trk receptors, allowing cellular responses that are highly context dependent, particularly in the nervous system and particularly with regard to the neurotrophin brain-derived neurotrophic factor (BDNF). Recent reports describe a variety of sophisticated regulatory mechanisms that contribute to such functional flexibility. Mechanisms described include regulation of trafficking of alternative BDNF transcripts, regulation of post-translational processing and secretion of BDNF, engagement of co-receptors that influence localization and signaling of p75 and Trk receptors, and control of trafficking of receptors in the endocytic pathway and during anterograde and retrograde axonal transport.

Recurrent group A tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant T cells.

"Strep throat" is highly prevalent among children, yet it is unknown why only some children develop recurrent tonsillitis (RT), a common indication for tonsillectomy. To gain insights into this classic childhood disease, we performed phenotypic, genotypic, and functional studies on pediatric group A (GAS) RT and non-RT tonsils from two independent cohorts. GAS RT tonsils had smaller germinal centers, with an underrepresentation of GAS-specific CD4 germinal center T follicular helper (GC-T) cells.

Circadian rhythm of redox state regulates membrane excitability in hippocampal CA1 neurons.

Behaviors, such as sleeping, foraging, and learning, are controlled by different regions of the rat brain, yet they occur rhythmically over the course of day and night. They are aligned adaptively with the day-night cycle by an endogenous circadian clock in the suprachiasmatic nucleus (SCN), but local mechanisms of rhythmic control are not established. The SCN expresses a ~24-hr oscillation in reduction-oxidation that modulates its own neuronal excitability.

Circadian redox rhythms in the regulation of neuronal excitability.

Oxidation-reduction reactions are essential to life as the core mechanisms of energy transfer. A large body of evidence in recent years presents an extensive and complex network of interactions between the circadian and cellular redox systems. Recent advances show that cellular redox state undergoes a ~24-h (circadian) oscillation in most tissues and is conserved across the domains of life.

Galaxy growth in a massive halo in the first billion years of cosmic history.

According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far.

Mechanisms and Medicines for Remyelination.

Demyelination of central nervous system axons, associated with traumatic injury and demyelinating diseases such as multiple sclerosis, causes impaired neural transmission and ultimately axon degeneration. Consequently, extensive research has focused on signaling systems that promote myelinating activity of oligodendrocytes or promote production of new oligodendrocytes from oligodendrocyte progenitor cells. Many receptor systems, notably including growth factor receptors and G protein-coupled receptors, control myelination.

Recent advances in understanding neurotrophin signaling.

The nerve growth factor family of growth factors, collectively known as neurotrophins, are evolutionarily ancient regulators with an enormous range of biological functions. Reflecting this long history and functional diversity, mechanisms for cellular responses to neurotrophins are exceptionally complex. Neurotrophins signal through p75 (NTR), a member of the TNF receptor superfamily member, and through receptor tyrosine kinases (TrkA, TrkB, TrkC), often with opposite functional outcomes.

A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood.

Detection of Ag-specific CD4(+) T cells is central to the study of many human infectious diseases, vaccines, and autoimmune diseases. However, such cells are generally rare and heterogeneous in their cytokine profiles. Identification of Ag-specific germinal center (GC) T follicular helper (Tfh) cells by cytokine production has been particularly problematic.

Cytokine-Independent Detection of Antigen-Specific Germinal Center T Follicular Helper Cells in Immunized Nonhuman Primates Using a Live Cell Activation-Induced Marker Technique.

A range of current candidate AIDS vaccine regimens are focused on generating protective HIV-neutralizing Ab responses. Many of these efforts rely on the rhesus macaque animal model. Understanding how protective Ab responses develop and how to increase their efficacy are both major knowledge gaps.

Spatio temporal population dynamics of the invasive diatom Didymosphenia geminata in central-southern Chilean rivers.

We document the distribution of Didymosphenia geminata in central-southern Chilean rivers and identify the chemical and physical factors associated with its presence/absence (p/a). Repeated surveys in five successive years provided evidence that D. geminata could be nearing a biogeographic equilibrium in the region.

CXCL13 is a plasma biomarker of germinal center activity.

Significantly higher levels of plasma CXCL13 [chemokine (C-X-C motif) ligand 13] were associated with the generation of broadly neutralizing antibodies (bnAbs) against HIV in a large longitudinal cohort of HIV-infected individuals. Germinal centers (GCs) perform the remarkable task of optimizing B-cell Ab responses. GCs are required for almost all B-cell receptor affinity maturation and will be a critical parameter to monitor if HIV bnAbs are to be induced by vaccination.

Intracellular LINGO-1 negatively regulates Trk neurotrophin receptor signaling.

Neurotrophins, essential regulators of many aspects of neuronal differentiation and function, signal via four receptors, p75, TrkA, TrkB and TrkC. The three Trk paralogs are members of the LIG superfamily of membrane proteins, which share extracellular domains consisting of leucine-rich repeat and C2 Ig domains. Another LIG protein, LINGO-1 has been reported to bind and influence signaling of p75 as well as TrkA, TrkB and TrkC.

BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms.

Follicular helper T cells (Tfh cells) are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of BCL6 in Tfh cells have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells.

LINGO-1 promotes lysosomal degradation of amyloid-β protein precursor.

Sequential proteolytic cleavages of amyloid-β protein precursor (AβPP) by β-secretase and γ-secretase generate amyloid β (Aβ) peptides, which are thought to contribute to Alzheimer's disease (AD). Much of this processing occurs in endosomes following endocytosis of AβPP from the plasma membrane. However, this pathogenic mode of processing AβPP may occur in competition with lysosomal degradation of AβPP, a common fate of membrane proteins trafficking through the endosomal system.