The Vehicle, 1969, Vol. 12 no. 1

Vol. 12, No. 1 Table of Contents A New LookNick Dagerpage 3 The RingSara Brinkerhoffpage 5 WaitingSara Brinkerhoffpage 6 Before Cotton FieldsSara Brinkerhoffpage 8 poemAnn Graffpage 9 The Socratic IronyMarcia Trostpage 11 poemNick Dagerpage 17 rainJim Elledgepage 18 LindaMarilyn Viveritopage 19 To You My FatherAnn Flemingpage 20 poemRoger Zulaufpage 24 GeographyJanet Andrewspage 25 Nagging ThoughtJanet Andrewspage 25 Let\u27s RunVerna L. Jonespage 27 Art Credits Kevin SheaCover Mike Dorseypages 4, 23, 28 Steve Williamspages 7, 16, 19, 24, 26 Jim Millerpages 10, 22 Dale Huberpage 13 Nick Dagerpage 3https://thekeep.eiu.edu/vehicle/1021/thumbnail.jp

The Vehicle, 1969, Vol. 12 no. 1

Vol. 12, No. 1 Table of Contents A New LookNick Dagerpage 3 The RingSara Brinkerhoffpage 5 WaitingSara Brinkerhoffpage 6 Before Cotton FieldsSara Brinkerhoffpage 8 poemAnn Graffpage 9 The Socratic IronyMarcia Trostpage 11 poemNick Dagerpage 17 rainJim Elledgepage 18 LindaMarilyn Viveritopage 19 To You My FatherAnn Flemingpage 20 poemRoger Zulaufpage 24 GeographyJanet Andrewspage 25 Nagging ThoughtJanet Andrewspage 25 Let\u27s RunVerna L. Jonespage 27 Art Credits Kevin SheaCover Mike Dorseypages 4, 23, 28 Steve Williamspages 7, 16, 19, 24, 26 Jim Millerpages 10, 22 Dale Huberpage 13 Nick Dagerpage 3https://thekeep.eiu.edu/vehicle/1021/thumbnail.jp

Renal-Retinal Ciliopathy Gene Sdccag8 Regulates DNA Damage Response Signaling

Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and degenerative kidney diseases that are frequently associated with extrarenal pathologies such as retinal degeneration, obesity, and intellectual disability. We recently identified mutations in a gene encoding the centrosomal protein SDCCAG8 as causing NPHP type 10 in humans. To study the role of Sdccag8 in disease pathogenesis, we generated a Sdccag8 gene-trap mouse line. Homozygous Sdccag8(gt/gt) mice lacked the wild-type Sdccag8 transcript and protein, and recapitulated the human phenotypes of NPHP and retinal degeneration. These mice exhibited early onset retinal degeneration that was associated with rhodopsin mislocalization in the photoreceptors and reduced cone cell numbers, and led to progressive loss of vision. By contrast, renal histologic changes occurred later, and no global ciliary defects were observed in the kidneys. Instead, renal pathology was associated with elevated levels of DNA damage response signaling activity. Cell culture studies confirmed the aberrant activation of DNA damage response in Sdccag8(gt/gt)-derived cells, characterized by elevated levels of γH2AX and phosphorylated ATM and cell cycle profile abnormalities. Our analysis of Sdccag8(gt/gt) mice indicates that the pleiotropic phenotypes in these mice may arise through multiple tissue-specific disease mechanisms

Meta- and Orthogonal Integration of Influenza ‘OMICs’ Data Reveals UBR4 as a Critical Regulator of M2 Ion Channel Membrane Trafficking

Systems-level analyses of the molecular interfaces between influenza A and its human host have provided considerable new insights into cellular circuits and processes that govern viral infection. However, apparent discordant results from various approaches, including RNAi screens and proteomics studies, have hampered leveraging of these findings to advance mechanistic and therapeutic knowledge. To collectively reconcile these datasets, we have performed a meta-analysis of previously unpublished primary datasets sets from 4 siRNA screens, along with results from an additional 4 RNAi screens, to rank prioritize host and restriction factors that were found to impact viral replication in multiple datasets. This approach enabled us to identify nearly 200 published factors, as well as the 57 previously unreported host proteins, with activities supported by multiple datasets, and indicate ~50% overlap of published genes when observed at the level of cellular pathways or biochemical complexes. Further integration of these data with published and experimentally generated protein interaction data revealed the landscape of biochemical interactions between 264 host proteins found to be essential for influenza A replication and 11 virally encoded proteins. Notably, we find that the putative E3 ligase UBR4 physically associates with the virally encoded M2 protein to direct it’s trafficking to the cellular membrane. Inhibition of UBR4 results in relocalization of M2 with the autophagosomal marker ARHI and also its degradation, resulting in a severe attenuation of late phase influenza A replication. The requirement for this host protein was found to be restricted to human, but not avian, strains of the virus, suggesting that adaptations that enable the appropriation of mammalian UBR4 may be critical to zoonotic transmission and/or pathogenesis. Taken together, the integrative analysis of influenza OMICs datasets illuminate a viral-host network of high confidence human proteins that are essential for influenza A replication, and furthermore uncovers a role for UBR4 in the trafficking of the virally-encoded M2 ion channel to the cell membrane to enable viral egress

Inhibitory Phosphorylation of Separase Is Essential for Genome Stability and Viability of Murine Embryonic Germ Cells

Activity of separase, a cysteine protease that cleaves sister chromatid cohesin at the onset of anaphase, is tightly regulated to ensure faithful chromosome segregation and genome stability. Two mechanisms negatively regulate separase: inhibition by securin and phosphorylation on serine 1121. To gauge the physiological significance of the inhibitory phosphorylation, we created a mouse strain in which Ser1121 was mutated to Ala (S1121A). Here we report that this S1121A point mutation causes infertility in mice. We show that germ cells in the mutants are depleted during development. We further demonstrate that S1121A causes chromosome misalignment during proliferation of the postmigratory primordial germ cells, resulting in mitotic arrest, aneuploidy, and eventual cell death. Our results indicate that inhibitory phosphorylation of separase plays a critical role in the maintenance of sister chromatid cohesion and genome stability in proliferating postmigratory primordial germ cells