Publication

circSLC45A4 is the main RNA splice isoform produced from its genetic locus and one of the highest expressed circRNAs in the developing human frontal cortex. Knockdown of this highly conserved circRNA in a human neuroblastoma cell line is sufficient to induce spontaneous neuronal differentiation, measurable by increased expression of neuronal marker genes. Depletion of circSlc45a4 in the developing mouse cortex causes a significant reduction of the basal progenitor pool and increases the expression of neurogenic regulators.

The neurodevelopmental origin of hyperactivity disorder has been suggested to involve the dopaminergic system, but the underlying mechanisms are still unknown. Here, transcription factors Lmx1a and Lmx1b are shown to be essential for midbrain dopaminergic (mDA) neuron excitatory synaptic inputs and dendritic development. Strikingly, conditional knockout (cKO) of Lmx1a/b in postmitotic mDA neurons results in marked hyperactivity. In seeking Lmx1a/b target genes, we identify positively regulated Slitrk2 and negatively regulated Slitrk5.

BACKGROUND:
Genetic defects of pediatric-onset inflammatory bowel disease (IBD) provide critical insights into molecular factors controlling intestinal homeostasis. NOX1 has been recently recognized as a major source of reactive oxygen species (ROS) in human colonic epithelial cells. Here we assessed the functional consequences of human NOX1 deficiency with respect to wound healing and epithelial migration by studying pediatric IBD patients presenting with a stop-gain mutation in NOX1.

In amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), spinal and lower brainstem motor neurons degenerate, but some motor neuron subtypes are spared, including oculomotor neurons (OMNs). The mechanisms responsible for this selective degeneration are largely unknown, but the molecular signatures of resistant and vulnerable motor neurons are distinct and offer clues to neuronal resilience and susceptibility. Here, we demonstrate that healthy OMNs preferentially express Synaptotagmin 13 (SYT13) compared to spinal motor neurons.

Porcine circovirus 3 (PCV3) has been identified as a putative swine pathogen with a subset of infections resulting in stillborn and mummified fetuses, encephalitis and myocarditis in perinatal, and periarteritis in growing pigs. Three PCV3 isolates were isolated from weak-born piglets or elevated stillborn and mummified fetuses. Full-length genome sequences from different passages and isolates (PCV3a1 ISU27734, PCV3a2 ISU58312, PCV3c ISU44806) were determined using metagenomics sequencing. Virus production in cell culture was confirmed by qPCR, IFA, and in situ hybridization.

Emerging immunotherapies with monoclonal antibodies against programmed cell death protein-1 (PD-1) have shown success in treating cancers. However, PD-1 signaling in neurons is largely unknown. We recently reported that dorsal root ganglion (DRG) primary sensory neurons express PD-1 and activation of PD-1 inhibits neuronal excitability and pain. Opioids are mainstay treatments for cancer pain, and morphine produces antinociception via mu opioid receptor (MOR). Here, we report that morphine antinociception and MOR signaling require neuronal PD-1.

Amyotrophic lateral sclerosis (ALS) is a serious disease characterized by the degeneration of motor neurons resulting in muscle weakness and paralysis. The neuroendocrine polypeptide VGF is localized in the central nervous system and peripheral endocrine neurons and is cleaved into several polypeptides with multiple functions. Previous studies revealed that VGF was decreased in the cerebrospinal fluid of ALS model mice and sporadic ALS patients. However, it is unknown which cells supply VGF in the spinal cord and a detailed localization is lacking.

Homer proteins are a component of the post-synaptic density of neurons that are necessary for the maintenance and consolidation of behavioral state. The dominant negative protein homer1a is rapidly increased by neuronal activity and sleep loss. Homer1a knockout mice with globally absent homer1a have reduced ability to sustain wakefulness during the active period. It is not known whether homer1a is required globally or in very specific brain regions or neurons for its role in maintaining wake.

Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of HIV as a potential "shock and kill" therapeutic for HIV cure.

Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR).