Igf1r Signaling Is Indispensable for Preimplantation Development and Is Activated via a Novel Function of E-cadherin

Insulin-like growth factor I receptor (Igf1r) signaling controls proliferation, differentiation, growth, and cell survival in many tissues; and its deregulated activity is involved in tumorigenesis. Although important during fetal growth and postnatal life, a function for the Igf pathway during preimplantation development has not been described. We show that abrogating Igf1r signaling with specific inhibitors blocks trophectoderm formation and compromises embryo survival during murine blastocyst formation. In normal embryos total Igf1r is present throughout the membrane, whereas the activated form is found exclusively at cell contact sites, colocalizing with E-cadherin. Using genetic domain switching, we show a requirement for E-cadherin to maintain proper activation of Igf1r. Embryos expressing exclusively a cadherin chimera with N-cadherin extracellular and E-cadherin intracellular domains (NcEc) fail to form a trophectoderm and cells die by apoptosis. In contrast, homozygous mutant embryos expressing a reverse-structured chimera (EcNc) show trophectoderm survival and blastocoel cavitation, indicating a crucial and non-substitutable role of the E-cadherin ectodomain for these processes. Strikingly, blastocyst formation can be rescued in homozygous NcEc embryos by restoring Igf1r signaling, which enhances cell survival. Hence, perturbation of E-cadherin extracellular integrity, independent of its cell-adhesion function, blocked Igf1r signaling and induced cell death in the trophectoderm. Our results reveal an important and yet undiscovered function of Igf1r during preimplantation development mediated by a unique physical interaction between Igf1r and E-cadherin indispensable for proper receptor activation and anti-apoptotic signaling. We provide novel insights into how ligand-dependent Igf1r activity is additionally gated to sense developmental potential in utero and into a bifunctional role of adhesion molecules in contact formation and signaling

LMFBR (LIQUID METAL FAST BREEDER REACTOR) REACTION RATE AND DOSIMETRY QUARTERLY PROGRESS REPORT JUNE JULY AUGUST 1971

This report describes progress in the USAEC-sponsored Interlaboratory LMFBR Reaction Rate (ILRR) program. This program has been established by RDT to develop a capability to accurately measure neutron-induced reaction rates for LMFBR fuels and materials development programs. The initial goal for the principal fission reactions, {sup 235}U, {sup 238}U, and {sup 239}Pu, is an accuracy to within {+-} 5 at the 95% confidence level. Accurate measurement of other fission and non-fission reactions will be required, but to a lesser accuracy, between {+-} 5 to 10% at the 95% confidence level. A secondary program objective is improvement in knowledge of the nuclear parameters involved in fuels and materials dosimetry measurements of neutron flux, spectra, fluence, and burnup. The accuracy goals of the ILRR program are severe; measurements of fast-neutron-induced reaction rates have not been rapidly moving toward this level of precision. Using a number of techniques in well established neutron environments of current interest for fast reactor development and critically evaluating the results will help establish existing levels of accuracy and indicate the scale of effort required for improvement. To accomplish the objectives of this program, reliable and accepted experimental values of reaction rates and ratios will be determined for various well established and permanent neutron fields. The Coupled Fast Reactivity Measurement Facility (CFRMF) at Aerojet Nuclear Company (ANC) is the first neutron field being studied because of the similarity of its spectrum to that of a fast reactor and the range and reproducibility of flux levels available for track etch, fission chamber, radiochemistry, and helium mass spectrometric measurements. Results of the CFRMF and other ILRR tests coupled with those of past and present EBR-II dosimetry tests will provide the improved and more precise values of nuclear parameters urgently needed for LMFBR fuels and materials development programs

LMFBR (LIQUID METAL FAST BREEDER REACTOR) READTION RATE AND DOSIMETRY 3RD QUARTERLY PROGRESS REPORT DECEMBER 1971 JANUARY FEBRUARY 1972

This report was compiled at the Hanford Engineering Development Laboratory operated by Westinghouse Hanford Company, a subsidiary of Westinghouse Electric Corporation, for the United States Atomic Energy Commission, Division of Reactor Development and Technology, under Contract No. AT (45-1) 2170. It describes technical progress made in the Interlaboratory LMFBR Reaction Rate Program during the reporting period. The Interlaboratory LMFBR Reaction Rate (ILRR) program has been established by USAEC/RDT to develop a capability to accurately measure neutron-induced reaction rates for LMFBR fuels and materials development programs. The initial goal for the principal fission reactions, {sup 235}U, {sup 238}U, and {sup 239}Pu, is an accuracy to within {+-}5 at the 95% confidence level. Accurate measurement of other fission and non-fission reactions will be required, but to a lesser accuracy, between {+-}5 to 10% at the 95% confidence level. A secondary program objective is improvement in knowledge of the nuclear parameters involved in fuels and materials dosimetry measurements of neutron flux, spectra, fluence, and burnup. These accuracy goals for the ILRR program are severe; measurements of fast-neutron-induced reaction rates have not been rapidly moving toward this level of precision. Using a number of techniques in well established neutron environments of current interest for fast reactor development and critically evaluating the results will help establish existing levels of accuracy and indicate the scale of effort required for improvement. To accomplish the objectives of this program, reliable and documented experimental values of reaction rates and ratios will be determined for various well established and permanent neutron fields. The Coupled Fast Reactivity Measurement Facility (CFRMF) at Aerojet Nuclear Company (ANC) is the first neutron field being studied because of the similarity of its spectrum to that of a fast reactor and the range and reproducibility of flux levels available for track etch, fission chamber, radiochemistry, and helium mass spectrometric measurements. Results of the CFRMF and other ILRR tests coupled with those of past and present EBR-II dosimetry tests will provide the improved and more precise values of nuclear parameters urgently needed for LMFBR fuels and materials development programs

Growing Rod Concepts: State Of The Art

Early-onset spinal deformities present multiple challenges to the surgeon. They may be rapidly progressive and unresponsive to conservative treatment, necessitating surgical intervention at an early age. This text attempts to provide a review of current literature and to summarize the authors' opinions. This paper attempts to concisely review available literature regarding the growing rod's inception, evolution, technique, results, and complications and answers some of the controversy still surrounding it. The growing rod is one of the first, most evolved, most popular and one of the most heatedly discussed technique of fusionless spinal instrumentation.Wo