Cross-talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification.

BACKGROUND: Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein-2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross-talk between EGFR and BMP2 signals in developing and adult growth plates. RESULTS: Using in vivo mouse models of conditional cartilage-targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR-deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2-deficient growth plates. EGFR-deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist. CONCLUSIONS: Cross-talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross-talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.

Antibody Titers Against Human Cytomegalovirus gM/gN and gB Among Pregnant Women and Their Infants.

Congenital CMV (cCMV) infection can affect infants born to mothers with preconceptional seroimmunity. To prevent cCMV due to nonprimary maternal infection, vaccines eliciting responses exceeding natural immunity may be required. Anti-gM/gN antibodies have neutralizing capacity in-vitro and in animal models, but anti-gM/gN antibodies have not been characterized among seroimmune pregnant women. Paired maternal and infant cord sera from 92 CMV seropositive mothers and their full-term or preterm infants were tested for anti-gM/gN antibody titers in comparison with anti-gB titers and neutralizing activity. Anti-gM/gN titers were significantly lower than anti-gB titers for all groups and did not correlate with serum neutralizing capacity. Further study is needed to determine if higher anti-gM/gN antibody titers might enhance serum neutralizing capacity among seropositive adults.

Examining the Relationship Between the Readability and Comprehensibility of Practice Test Questions and Failure Rates on Learner's Permit Knowledge Tests.

Purpose The readability and comprehensibility of Learner's Permit Knowledge Test practice questions and the relationship with test failure rates across states and the District of Columbia were examined. Method Failure rates were obtained from department representatives. Practice test questions were extracted from drivers' manuals and department websites and examined for readability using Flesch-Kincaid Grade Level and comprehensibility using Question Understanding Aid. The influence of readability and comprehensibility on test failure rates was explored. Results The average failure rate from reporting jurisdictions was 42.76%. In total, 11 out of 28 jurisdictions reported that test takers fail more than half the time, while 25 out of 28 reported that test takers fail at least a quarter of the time. While 33.09% of the variability in failure rates could be accounted for by syntactic complexity of the questions, 54.18% could be accounted for by the reading ease. Discussion With few exceptions, test failure rates are systematically high across the United States. The current findings suggest that these tests may be inappropriately biased against individuals with lower levels of literacy and language ability. Implications for test developers and clinicians are discussed.