Anti-FICD monoclonal antibody Made to order

Objective: To develop the Family Impact of Childhood Disability Scale (FICD) to assess subjective interpretation or "primary appraisal" of parents regarding the impact of a child with developmental disabilities on the family. Method: A random sample of 87 families was assessed while children with developmental disabilities were in the preschool years. After 7 years had elapsed, 64 of these families were interviewed again when the children were in the preteen years. A set of standardized self-report measures provided mother and father views of child, parent, and family functioning. Results: The FICD demonstrated adequate internal consistency, with some evidence of discriminant and predictive validity. The FICD total score, based on the discrepancy between positive and negative subscale scores, was found to be a significant predictor of future parenting stress of mothers and of fathers, even when controlling for other important explanatory variables such as marital adjustment and level of disability in a child. Conclusions: The 15-item FICD offers a brief assessment of both positive and negative parent appraisals, with a total discrepancy score that predicts long-term parenting stress.

AMPylation is an inactivating modification that alters the activity of the major endoplasmic reticulum (ER) chaperone BiP to match the burden of unfolded proteins. A single ER-localised Fic protein, FICD (HYPE), catalyses both AMPylation and deAMPylation of BiP. However, the basis for the switch in FICD's activity is unknown. We report on the transition of FICD from a dimeric enzyme, that deAMPylates BiP, to a monomer with potent AMPylation activity. Mutations in the dimer interface, or of residues along an inhibitory pathway linking the dimer interface to the enzyme's active site, favour BiP AMPylation in vitro and in cells. Mechanistically, monomerisation relieves a repressive effect allosterically propagated from the dimer interface to the inhibitory Glu234, thereby permitting AMPylation-competent binding of MgATP. Moreover, a reciprocal signal, propagated from the nucleotide-binding site, provides a mechanism for coupling the oligomeric state and enzymatic activity of FICD to the energy status of the ER.