NEURAL EXPRESSION AND FUNCTION OF AUTISM CANDIDATE GENES IN ZEBRAFISH

The Autism Spectrum Disorders (ASD) refer to a large heterogeneous set of developmental disorders defined by two behavioral domains: 1) Impairment of social comprehension and abnormal development of social communication, and 2) the presence of stereotypical and repetitive behaviors. The etiology of ASD is complex, with both genetic and environmental components. De novo and inherited mutations within DPP6 and PSMD12 have been identified within individuals diagnosed with ASD suggesting an etiologic role. Understanding the functionality of these genes could lead novel treatments for ASD. Zebrafish were utilized as a model system for the assessment of functionality of the orthologous genes dpp6a, dpp6b, and psmd12. Zebrafish are an ideal model system for neurological disorders because they develop quickly, share many fundamental brain structures and capacities with humans, and are genetically malleable. This work demonstrates commercially available antibodies designed to DPP6 bind promiscuously; therefore, necessitating a continued search for specific antibodies. In addition, three TALE Nucleases (TALENs) were designed to specifically target the psmd12 gene. In order to elucidate psmd12 mutants, genotyping assays were designed and a specific antibody was ascertained. These tools will be critical in the development of an allelic series and functional assessment of psmd12

JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse.

Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. Here, we provide multiple lines of evidence that JAKMIP1 is a component of polyribosomes and an RNP translational regulatory complex that includes fragile X mental retardation protein, DEAD box helicase 5, and the poly(A) binding protein cytoplasmic 1. JAKMIP1 loss dysregulates neuronal translation during synaptic development, affecting glutamatergic NMDAR signaling, and results in social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors in the mouse. These findings define an important and novel role for JAKMIP1 in neural development and further highlight pathways regulating mRNA translation during synaptogenesis in the genesis of neurodevelopmental disorders

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7