Reliability of the rabbit postero‐lateral spinal fusion model: A meta‐analysis

The rabbit model of spinal fusion with the autogenous iliac crest bone graft (ICBG) control is widely used to evaluate bone graft substitutes and enhancers. This study examined the reliability of this model using meta‐analysis. A systematic literature search from January 1995 to May 2011 identified 56 studies, involving 733 animals. The primary outcome was fusion success calculated as logit event rate. Study design, surgical technique, rabbit characteristics (gender, species, age, weight), and institution were analyzed. Overall fusion success was 52.4%. Important positive variables were time‐point >4 weeks, ICBG dose >1 cm³, initial weight of animals ≥3 kg, level at L4‐5 or L5‐6, and age ≥6 months. Inter‐ and intra‐institutional reliability was excellent. The rabbit model ICBG control group is reliable, although several factors can affect results. Fusion under normal handling occurs reliably in 5 weeks. The volume of bone graft should be >1 cm³ but no benefits are present with >2 cm³. The animals should weigh a minimum of 3 kg and be at least 6 months old. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1261–1269, 2013     

CFTR (ABCC7) is a hydrolyzable-ligand-gated channel

As the product of the gene mutated in cystic fibrosis, the most common genetic disease of Caucasians, CFTR is an atypical ABC protein. From an evolutionary perspective, it is apparently a relatively young member of the ABC family, present only in metazoans where it plays a critical role in epithelial salt and fluid homeostasis. Functionally, the membrane translocation process it mediates, the passive bidirectional diffusion of small inorganic anions, is simpler than the vectorial transport of larger more complex substrates (“allocrites”) by most ABC transporters. However, the control of the permeation pathway which cannot go unchecked is necessarily more stringent than in the case of the transporters. There is tight regulation by the phosphorylation/dephosphorylation of the unique CFTR R domain superimposed on the basic ABC regulation mode of ATP binding and hydrolysis at the dual nucleotide binding sites. As with other ABCC subfamily members, only the second of these sites is hydrolytic in CFTR. The phosphorylation and ATP binding/hydrolysis events do not strongly influence each other; rather, R domain phosphorylation appears to enable transduction of the nucleotide binding allosteric signal to the responding channel gate. ATP hydrolysis is not required for either the opening or closing gating transitions but efficiently clears the ligand-binding site enabling a new gating cycle to be initiated.     

Does Physical Activity in Adolescence Have Site‐Specific and Sex‐Specific Benefits on Young Adult Bone Size,Content, and Estimated Strength?

The long‐term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSI_p) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSI_c) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z‐scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSI_p, p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSI_p in males, and greater CoA, CoC, and TrC in females. © 2014 American Society for Bone and Mineral Research.     

Spontaneous solubilization of membrane-bound human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells.

The testis isozyme of angiotensin-converting enzyme (ACE; EC 3.4.15.1) is a membrane-bound protein that, apart from the first 35 N-terminal residues, is identical to the C-terminal half of somatic ACE and contains the same putative C-terminal membrane anchor. Stable transfection of Chinese hamster ovary (CHO) cells with an expression vector containing the full-length human testis ACE cDNA results in the expression of two forms of recombinant human testis ACE (hTACE): membrane-bound ACE and, surprisingly, large quantities (up to 3 mg/liter) of soluble hTACE in the conditioned medium. Both forms are fully active and are physicochemically similar. However, by phase separation in Triton X-114, the soluble enzyme is hydrophilic, as is an anchor-minus mutant hTACE recovered from the medium of CHO cells transfected with a vector that contains a 3'-truncated testis ACE cDNA lacking the sequence encoding the membrane anchor. In contrast, the membrane-bound hTACE is amphipathic but is converted to a hydrophilic form on treatment with trypsin. The data establish that in ACE the hydrophobic sequence near the C terminus is necessary for membrane anchoring. Moreover, in CHO cells, membrane-bound hTACE is apparently solubilized by proteolytic cleavage of this anchor. A similar mechanism may account for the release of endothelial ACE in vivo to generate serum ACE and more generally for the constitutive processing and solubilization of analogously anchored proteins such as the amyloid precursor protein, among others. The release of membrane-bound ACE in CHO cells may, therefore, provide a useful system for the study of membrane-protein-solubilizing proteases.     

Slow weight gain is associated with increased periodic breathing in healthy infants

To investigate the hypothesis that weight gain can influence periodic breathing in healthy infants, we prospectively studied, by nocturnal pneumogram technique, respiration and heart rate in 99 full-term infants during the first month of life. Eighty-eight infants had a repeat study at about 2 months of age. Pneumograms were analyzed visually for percent periodic breathing (%PB), and by computer for mean respiratory rate and mean heart rate. We found a median %PB of 0.9 initially and of 0.3 at about 2 months of age. The 95th percentile was 13.5 at 2 weeks and 7.3 at 2 months, higher than previously reported. Between the two ages tested, %PB was inversely correlated with weight gain (P < 0.001, (0.03, respectively). Infants with greater weight gain had a greater fall in %PB (P < 0.03). We conclude that in the first 2 months of life, slow weight gain is associated with increased periodic breathing. Pediatr Pulmonol. 1994; 17:22–25. © 1994 Wiley-Liss, Inc.