To cooperatively transport a large load, it is important that carriers conform in their efforts and align their forces. A downside of behavioural conformism is that it may decrease the group's responsiveness to external information. Combining experiment and theory, we show how ants optimize collective transport. On the single-ant scale, optimization stems from decision rules that balance individuality and compliance. Macroscopically, these rules poise the system at the transition between random walk and ballistic motion where the collective response to the steering of a single informed ant is maximized. We relate this peak in response to the divergence of susceptibility at a phase transition. Our theoretical models predict that the ant-load system can be transitioned through the critical point of this mesoscopic system by varying its size; we present experiments supporting these predictions. Our findings show that efficient group-level processes can arise from transient amplification of individual-based knowledge.

Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-a (G6Pase-a), a ninetransmembrane domain, endoplasmic reticulum-associated protein expressed primarily in the liver and kidney. Previously, we showed that infusion of an adeno-associated virus (AAV) serotype 2 vector carrying murine G6Pase-a (AAV2-G6Pase-a) into neonatal GSD-Ia mice failed to sustain their life beyond weaning. We now show that neonatal infusion of GSD-Ia mice with an AAV serotype 1-G6Pase-a (AAV1-G6Pase-a) or AAV serotype 8-G6Pase-a (AAV8-G6Pase-a) results in hepatic expression of the G6Pase-a transgene and markedly improves the survival of the mice. However, only AAV1-G6Pase-a can achieve significant renal transgene expression. A more effective strategy, in which a neonatal AAV1-G6Pase-a infusion is followed by a second infusion at age 1 week, provides sustained expression of a complete, functional, G6Pase-a system in both the liver and kidney and corrects the metabolic abnormalities in GSD-Ia mice for the 57 week length of the study. This effective use of gene therapy to correct metabolic imbalances and disease progression in GSD-Ia mice holds promise for the future of gene therapy in humans. Gene Therapy (2005) 13, 321-329.

The glucose-6-phosphatase (Glc-6-Pase) family comprises two active endoplasmic reticulum (ER)-associated isozymes: the liver/kidney/intestine Glc-6-Pase-␣ and the ubiquitous Glc-6-Pase-␤. Both share similar kinetic properties. Sequence alignments predict the two proteins are structurally similar. During glucose 6-phosphate (Glc-6-P) hydrolysis, Glc-6-Pase-␣, a nine-transmembrane domain protein, forms a covalently bound phosphoryl enzyme intermediate through His 176 , which lies on the lumenal side of the ER membrane. We showed that Glc-6-Pase-␤ is also a nine-transmembrane domain protein that forms a covalently bound phosphoryl enzyme intermediate during Glc-6-P hydrolysis. However, the intermediate was not detectable in Glc-6-Pase-␤ active site mutants R79A, H114A, and H167A. Using [ 32 P]Glc-6-P coupled with cyanogen bromide mapping, we demonstrated that the phosphate acceptor in Glc-6-Pase-␤ is His 167 and that it lies inside the ER lumen with the active site residues, Arg 79 and His 114 . Therefore Glc-6-Pase-␣ and Glc-6-Pase-␤ share a similar active site structure, topology, and mechanism of action.The glucose-6-phosphatase (Glc-6-Pase) 1 family is composed of three proteins: Glc-6-Pase-␣ (1-4), Glc-6-Pase-␤ (5-7) (previously known as UGRP (ubiquitously expressed Glc-6-Pase related protein)), and islet-specific Glc-6-Pase-related protein (8,9). Whereas Glc-6-Pase-␣ and Glc-6-Pase-␤ are functional phosphohydrolases, the islet-specific Glc-6-Pase-related protein lacks enzymatic activity.The prototype of the family, Glc-6-Pase-␣, is a 357-amino acid, nine-transmembrane domain, endoplasmic reticulum (ER)-associated protein (10, 11), which is expressed primarily in the liver, kidney, and intestine (12, 13). Glc-6-Pase-␣ catalyzes the hydrolysis of glucose 6-phosphate (Glc-6-P) to glucose in the terminal step of gluconeogenesis and glycogenolysis (13). Between meals, the resulting release of glucose to the blood maintains glucose homeostasis. Naturally occurring loss of function mutations in Glc-6-Pase-␣ cause glycogen storage disease type Ia, a disorder that is characterized by loss of blood glucose homeostasis and disorders of glycogen and lipid metabolism (reviewed in Refs. 14 and 15).Glc-6-Pase-␤ is a ubiquitously expressed, 346-amino acid membrane protein that shares a 36% sequence identity to Glc-6-Pase-␣ (5-7). Despite the absence of any apparent ER retention motif, Glc-6-Pase-␤ is also localized in the ER membrane (6), although its orientation in the membrane is not known. The subcellular localization of the Glc-6-Pase-␤ active site is not known, although it is assumed to be similar to Glc-6-Pase-␣. Both Glc-6-Pase-␤ and Glc-6-Pase-␣ couple with the Glc-6-P transporter to form an active Glc-6-Pase complex, and both share similar kinetic properties with respect to Glc-6-P hydrolysis (6).The active site of Glc-6-Pase-␣ was originally identified by the presence of a conserved phosphatase signature motif found in lipid phosphatases, acid phosphatases, and vanadium haloperoxidases (16,17). This motif was show...

A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. ABSTRACT Dental pulp cells can differentiate toward an odontoblastic phenotype to produce reparative dentin beneath caries lesions. However, the mechanisms involved in pulp cell differentiation under pro-inflammatory stimuli have not