Foreword: Control and Conservation of Lampreys Beyond 2020 – Proceedings from the 3rd Sea Lamprey International Symposium (SLIS III)

This special issue summarizes outcomes from the 3rd Sea Lamprey International Symposium (SLIS III; Fig. 1) held 28 July – 2 August 2019 at Wayne State University in Detroit, Michigan, U.S.A. The first two symposia (SLIS I and SLIS II) were held 30 July – 8 August 1979 at Northern Michigan University in Marquette, Michigan and 14–18 August 2000 at Lake Superior State University in Sault Ste. Marie, Michigan, respectively. The published volumes from these symposia in 1980 (Canadian Journal of Fisheries and Aquatic Sciences, Volume 37, Issue 11) and 2003 (Journal of Great Lakes Research Volume 29, Supplement 1) have been invaluable references for the broader scientific community and for management agencies around the Laurentian Great Lakes; cited over 4800 and 3300 times, respectively. SLIS III was attended by over 150 scientists, biologists, resource managers, graduate students, and Commission advisors, including participants from Australia, Canada, China, Japan, New Zealand, Portugal, Spain, the United Kingdom, and the United States (Fig. 2). Similar to SLIS I and SLIS II, the goals of SLIS III were to provide a forum to (i) update and publish information on sea lamprey control and research on lampreys since SLIS II, (ii) exchange knowledge and ideas to bring practitioners to a common plateau of understanding, and (iii) develop innovative initiatives and stimulate new vigor in efforts to control sea lamprey in the Great Lakes and to conserve lampreys in their native ranges. The emphasis on conservation of lampreys is unique to SLIS III and reflects a heightened international recognition that scientific and management advances supporting sea lamprey control in the Great Lakes can benefit the global effort to conserve native lampreys and vice versa

Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor beta Signaling

BACKGROUND: The X-chromosome gene USP9X encodes a deubiquitylating enzyme that has been associated with neurodevelopmental disorders primarily in female subjects. USP9X escapes X inactivation, and in female subjects de novo heterozygous copy number loss or truncating mutations cause haploinsufficiency culminating in a recognizable syndrome with intellectual disability and signature brain and congenital abnormalities. In contrast, the involvement of USP9X in male neurodevelopmental disorders remains tentative.METHODS: We used clinically recommended guidelines to collect and interrogate the pathogenicity of 44 USP9X variants associated with neurodevelopmental disorders in males. Functional studies in patient-derived cell lines and mice were used to determine mechanisms of pathology.RESULTS: Twelve missense variants showed strong evidence of pathogenicity. We define a characteristic phenotype of the central nervous system (white matter disturbances, thin corpus callosum, and widened ventricles); global delay with significant alteration of speech, language, and behavior; hypotonia; joint hypermobility; visual system defects; and other common congenital and dysmorphic features. Comparison of in silico and phenotypical features align additional variants of unknown significance with likely pathogenicity. In support of partial loss-of-function mechanisms, using patient-derived cell lines, we show loss of only specific USP9X substrates that regulate neurodevelopmental signaling pathways and a united defect in transforming growth factor signaling. In addition, we find correlates of the male phenotype in Usp9x brain-specific knockout mice, and further resolve loss of hippocannpal-dependent learning and memory.CONCLUSIONS: Our data demonstrate the involvement of USP9X variants in a distinctive neurodevelopmental and behavioral syndrome in male subjects and identify plausible mechanisms of pathogenesis centered on disrupted transforming growth factor beta signaling and hippocampal function.Genetics of disease, diagnosis and treatmen