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The cytokine interleukin 6 (IL-6) signals via the IL-6 α-receptor (IL-6Rα or IL-6R) in complex with the gp130 β-receptor. Cell type restricted expression of the IL-6R limits the action of IL-6 mainly to hepatocytes and some immune cells. Here, we show that IL-6 also binds to the IL-11 α receptor (IL-11Rα or IL-11R) and induces signaling via IL-11R:gp130 complexes, albeit with a lower affinity compared to IL-11. Antagonistic antibodies directed against IL-11R, but not IL-6R, inhibit IL-6 signaling via IL-11R:gp130 receptor complexes. Notably, IL-11 did not cross-react with IL-6R. IL-11R has also been identified as an alternative α receptor for the CNTF/IL-6-derived chimeric cytokine IC7, which has recently been shown to induce weight loss in mice. Accordingly, the effects of therapeutic monoclonal antibodies against IL-6 or IL-6R, which both block IL-6 signaling, may be slightly different. These findings provide new insights into IL-6 signaling and therefore offer new potential therapeutic intervention options in the future., (© 2024 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses. To enable tailor-made generation of Hyper-cytokines, we developed inactive split-cytokine-precursors adapted for posttranslational reassembly by split-intein mediated protein trans-splicing (PTS). We identified cutting sites within IL-6 (E 134 /S 135 ) and IL-11 (G 116 /S 117 ) and obtained inactive split-Hyper-IL-6 and split-Hyper-IL-11 cytokine precursors. After fusion with split-inteins, PTS resulted in reconstitution of active Hyper-cytokines, which were efficiently secreted from transfected cells. Our strategy comprises the development of a background-free cytokine signaling system from reversibly inactivated precursor cytokines.

New dibenzo[24]crown-8 ether derivatives were prepared that contain appendages with thioether donors that can coordinate to a metal ion. These macrocycles were then combined with 1,2-bis(pyridinium) ethane axles to create two types of [2]rotaxane ligands; those with the four thioether donors on the crown ether and those with six donor groups, four from the crown ether and two more attached to the stoppering groups of the dumbbell. The crown ethers and both types of [2]rotaxane ligands were allowed to react with Ag(I) ions to form metal-organic rotaxane framework (MORF) style coordination polymers. The interlocked hexadentate ligand forms the first example of a new type of lattice containing interwoven frameworks resulting from both interpenetration of frameworks due to the presence of an interlocked ligand and more classical interpenetration of independent frameworks., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We investigated predictors of affective responses for 125 parents (77 mothers, 48 fathers) of children with various types of cancer who varied in time of diagnosis from newly diagnosed to 13 years following cancer treatment. The primary rationale of the investigation was to determine whether cognitive appraisals, perceived social supports, and caregivers' perceptions of children's behavior would predict affective responses differentially for mothers and fathers. We defined affectivity as self-reported depressive symptoms, and state and trait anxiety symptoms. Parents did not differ on any of the variables, including affective responses, although differential predictors of affective responses were revealed for mothers and fathers. Affiliation-related attributions were associated with affective responses for mothers, and achievement-related attributions and perceived social support were associated with affective responses for fathers., (Copyright 2001 John Wiley & Sons, Ltd.)

Assessed the influence of children's attribution style, coping style, social competence, parent coping, and demographic variables on the psychosocial adjustment of 86 pediatric oncology patients. Utilizing hierarchical multiple regression procedures, nearly one half of the variance in child depression was predicted by children's avoidance coping, depressive attributional style, and social competence. Child anxiety was predicted by a depressive attributional style, avoidance coping, and age at diagnosis. Child externalizing behavior was predicted by a depressive attributional style, parents' anxiety and SES. Implications for interventions and future research are discussed.

Evaluated the use of scheduled awakenings to eliminate sleepwalking using a noncurrent multiple baseline design across three subjects with persistent sleep-walking. Treatment procedure involves having parents awaken children several hours after they go to sleep and just before the typical time of the sleepwalking episode. This intervention proved immediately successful in eliminating sleep-walking in all three children. Treatment effects were maintained at 3 and 6 months posttreatment. Implications for intervention and future research are discussed.

Investigated the validity of the Child-Adult Medical Procedure Interaction Scale-Revised (CAMPIS-R) using multiple concurrent objective and subjective measures of child distress, approach-avoidance behavior, fear, pain, child cooperation, and parents' perceived ability to help their preschool children during routine immunizations. Parents', staffs', and children's behaviors in the treatment room were videotaped and coded. Results indicate that the validity of the CAMPIS-R codes of Child Coping and Distress, Parent Distress Promoting and Coping Promoting, and Staff Distress Promoting and Coping Promoting behavior were supported, with all significant correlations being in the predicted direction. An unanticipated finding was that the child, parent, and staff Neutral behaviors were inversely related to some measures of distress and positively related to some measures of coping. Interobserver reliability was high for each CAMPIS-R code.

Assessed the influence of adult in-session behavior and psychological variables on 77 preschool children's coping and distress during routine immunizations. Maternal anxiety was not related to the behavior of the parent, staff, or child. However, in-session behavior by one person was highly correlated with in-session behavior by the other people in the treatment room. The effects of parent and staff in-session behaviors, previous child medical experience, and maternal anxiety on child distress and coping was examined using hierarchical multiple regression procedures. Child coping was predicted by parent and staff behavior whereas child distress was predicted by parent behavior and by the level of the child's distress during previous medical and dental experiences. Implications for intervention and future research are discussed.