The Tumor Suppressor HHEX Inhibits Axon Growth when Prematurely Expressed in Developing Central Nervous System Neurons

Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present only in trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension

ECJ judges read the morning papers. Explaining the turnaround of European citizenship jurisprudence

Recent jurisprudence of the European Court of Justice (ECJ) marks a striking shift towards a more restrictive interpretation of EU citizens’ rights. The Court's turnaround is not only highly relevant for practical debates about ‘Social Europe’ or ‘welfare migration’, but also enlightening from a more general, theoretical viewpoint. Several recent studies on the ECJ have argued that the Court is largely constrained by member state governments’ threats of legislative override and non-compliance. We show that an additional mechanism is necessary to explain the Court's turnaround on citizenship. While the ECJ extended EU citizens’ rights even against strong opposition by member state governments, its recent shift reflects changes in the broader political context, i.e., the politicization of free movement in the European Union (EU). The article theorises Court responsiveness to politicization and demonstrates empirically, how the Court's jurisprudence corresponds with changing public debates about EU citizenship

Exile Vol. XLVI No. 1

44th Year Title Page 3 Epigraph by Ezra Pound 5 Statement of Policy 6 Table of Contents 7 Contributors Notes 37 Editorial Board 38 ART Incredible Lines by David Tulkin \u2701 8 Untitled by David Tulkin \u2701 12 Untitled by Patrick Yingling \u2703 18 Sculpted Body by David Tulkin \u2701 20 Untitled by Tanya Sheremeta \u2701 25 Untitled by David Tulkin \u2701 28 Untitled by Dena Behi \u2701 36 POETRY Wednesday by Mary Ann T. Davis \u2700 9 Music by Jessica Kramer \u2703 10-11 Worship During the Rainy Season by Allison Armbrister \u2701 19 Mercy by Mary Ann T. Davis \u2700 26-27 Albino Lizard by Matthew Martz \u2702 29 Filling of Lake Cumberland, 1951 by Allison Armbrister \u2701 35 PROSE Storm Drain by Matthew Martz \u2702 13-17 Creases by Stephanie M. Vaccaro \u2701 21-24 When It Rains by Matthew Martz \u2702 30-34 Statement of Policy This semester Exile instituted a new policy limiting submissions to those not involved in the production of the magazine. As always, all submissions are reviewed on an anonymous basis, and all editorial decisions are shared equally among the members of the Editorial Board. -6 Cover Art Untitled by Dena Behi \u2701 / Back Cover Art Untitled by Tanya Sheremeta \u2701 -38 Printed by Printing Arts Press -38 Matthew Martz, Albino Lizard, Storm Drain and When It Rains , redacted due to copyright restrictions

Bone Health in a Nonjaundiced Population of Children with Biliary Atresia

Objectives. To assess bone health in a cohort of nonjaundiced children with biliary atresia (BA) and the effect of growth and development on bone outcomes. Methods. Children ages one to eighteen years receiving care from Children's Hospital of Philadelphia were recruited. Each child was seen once and assessed for growth, pubertal development, concurrent medications, bilirubin, ALT, albumin, vitamin D status, bone mineral density (BMD), and bone mineral content (BMC) of the lumbar spine and whole body. Results. BMD declined significantly with age, and upon further analysis with a well-phenotyped control cohort, it was found that BMC was significantly decreased for both lumbar spine and whole body, even after adjustment for confounding variables. An age interaction was identified, with older subjects having a significantly greater impairment in BMC. Conclusions. These preliminary results demonstrate that children with BA, including those without jaundice, are likely to have compromised bone health even when accounting for height and puberty, which are common confounding factors in chronic disease. Further investigation is needed to identify the determinants of poor bone mineral status and to develop strategies to prevent osteoporosis later in life

Banner News

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Shifting the Intellectual Authority in Science Classrooms from Teachers to Students: How Novice Teachers Use Tools to Analyze and Advance Practice

To meet the immense challenges our society faces in areas such as energy, health, and environmental protection, we, as science teachers and teacher educators, need to invest in the creation of classroom cultures that turn the intellectual heavy lifting over to the students while developing students’ identities as competent learners. Our vision is that classrooms are both intellectually rigorous—accountable to important ideas and practices in the discipline—and uncompromisingly responsive to students’ developing scientific ideas. Problematically, this type of teaching is currently rare in science classrooms (Corcoran & Gerry, 2011; Kane & Staiger, 2012; Pasley, 2002; Roth & Garnier, 2007; Weiss, Banilower, McMahon, & Smith, 2001). Studies of novice teachers indicate that “the use of analogies, the implementation of strategic approaches to questioning, and the elicitation of student understandings remained virtually absent from their dialogue in class” (Hogan, Rabinowitz, & Craven, 2003, p. 243). Creating rigorous and responsive science learning environments that are the norm rather than the exception in the American educational system is thus a grandscale inquiry project that will require decades of collaboration and investigation to generate a shared vision of quality teaching and learning. The first-year teachers who co-authored this paper are leading this charge. They were one of the first cohorts to complete a teacher education program that focused on learning and inquiring into a core set of ambitious science teaching practices—practices that focus students’ intellectual work on complex problems rather than the typical emphases on activities and procedural talk; are adaptive to students’ needs and thinking; and maintain rigorous standards of achievement for everyone, enabling learners of all backgrounds to succeed at high-quality work (Fennema, Franke, Carpenter, & Carey, 1993; Hill, Rowan, & Ball, 2005; Lampert & Graziani,2009; Newmann & Associates, 1996;)