The presentation of secreted axon guidance factors plays a major role in shaping central nervous system (CNS) connectivity. Recent work suggests that heparan sulfate (HS) regulates guidance factor activity; however, the in vivo axon guidance roles of its carrier proteins (heparan sulfate proteoglycans, or HSPGs) are largely unknown. Here we demonstrate through genetic analysis in vivo that the HSPG Syndecan (Sdc) is critical for the fidelity of Slit repellent signaling at the midline of the Drosophila CNS, consistent with the localization of Sdc to CNS axons. sdc mutants exhibit consistent defects in midline axon guidance, plus potent and specific genetic interactions supporting a model in which HSPGs improve the efficiency of Slit localization and/or signaling. To test this hypothesis, we show that Slit distribution is altered in sdc mutants and that Slit and its receptor bind to Sdc. However, when we compare the function of the transmembrane Sdc to a different class of HSPG that localizes to CNS axons (Dallylike), we find functional redundancy, suggesting that these proteoglycans act as spatially specific carriers of common HS structures that enable growth cones to interact with and perceive Slit as it diffuses away from its source at the CNS midline.

Although alcohol use disorders (AUDs) adversely affect women, research on efficacious treatments for women is limited. In this randomized efficacy trial of 102 heterosexual women with AUDs, the authors compared alcohol behavioral couple therapy (ABCT) and alcohol behavioral individual therapy (ABIT) on percentage of days abstinent (PDA) and percentage of days of heavy drinking (PDH) over 6 months of treatment and 12 months of posttreatment follow-up. Baseline relationship functioning and comorbid disorders were tested as moderators of outcome. Piecewise linear growth models were used to model outcomes. During treatment, women increased their PDA and decreased their PDH, with significantly greater improvements in ABCT than in ABIT (d = 0.59 for PDA; d = 0.79 for PDH). Differences favoring ABCT were maintained during follow-up. Women with poorer baseline relationship functioning improved more on PDA during treatment with ABCT than with ABIT. For PDH, results during treatment and follow-up favored ABCT for women with better baseline relationship functioning. ABCT resulted in better outcomes than ABIT for women with Axis I disorders at the end of follow-up (PDA), and for women with Axis II disorders at the end of treatment (PDA) and at the end of follow-up (PDH).

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