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The tumour stroma is believed to contribute to some of the most malignant characteristics of epithelial tumours. However, signalling between stromal and tumour cells is complex and remains poorly understood. [...]

Ligands of the transforming growth factor-beta (TGF-beta) superfamily are involved in numerous developmental and disease processes. TGF-beta, activins, and nodal ligands operate through the highly homologous Smad2 and Smad3 intracellular mediators. Smad2 mutants exhibit early embryonic lethality, while Smad3 mutants are viable, but show a plethora of postnatal phenotypes, including immune dysfunction and skeletal abnormalities. Previously, we have shown that the Smad2 and Smad3 genes function cooperatively during liver morphogenesis. Here we show that Smad2 and Smad3 are required at a full dosage for normal embryonic development. Animals lacking one allele of each gene exhibit a variably penetrant phenotype in which structures in the anterior and ventral midline are reduced or lost; additionally, we demonstrate that this craniofacial defect and the previously reported hepatic phenotypes are both due to defects in the definitive endoderm. A reduction of endodermal gene expression as well as a failure to displace the visceral endoderm occurs despite the formation of a normal foregut pocket. This precedes any defects in anterior patterning and likely causes the abnormalities observed in craniofacial and midline development, as well as hepatogenesis. Keywords: Endoderm; Smad; TGF-beta; Holoprosencephaly; Hex; Foxa2; Craniofacial; Liver

Author(s): Lizhao Wu [1]; Alain de Bruin [1]; Harold I. Saavedra [1]; Maja Starovic [2]; Anthony Trimboli [1]; Ying Yang [3]; Jana Opavska [1]; Pamela Wilson [1, 4]; John C. [...]

Compares survey findings from 1971 and 1981 on university student perceptions and attitudes on environmental/energy questions. Five major categories were assessed and significant differences were observed between the surveys. A more materialistic lifestyle with less concern for environmental issues and concerns was indicated in the 1981 survey. (ML)

A survey examined secondary school teachers' perceptions of the effects of program, student, and teacher evaluations on instructional improvement. Results indicated that student evaluation was most effective in influencing teachers to revise their instruction. Teacher and program evaluations appeared to be ineffective as change agents. (MH)

Results of this study, done with underachieving ninth graders, indicate that flow charting as a structure for basic skills instruction can be considered as effective as the traditional approach. (MK)

The chemical shift of the phosphorus resonance of various nucleotides has been studied as a function of pH in the absence and presence of ribonuclease A. The 31P-signal of the nucleotides shifts upfield upon protonation of the phosphate moiety. Thus titration curves and pK values are obtained when the 31P chemical shift is plotted against the pH value. The titration curves are analyzed in terms of interactions of the phosphate group with the base or ribose moieties of the nucleotide itself or with amino-acid side chains of the active site of ribonuclease A. The chemical shift of the phosphorus magnetic resonance of cytidine 2′-phosphate when this nucleotide is bound to ribonuclease A resembles that of the dianionic form of the free compound. Proton magnetic resonance studies indicated that the histidine residue 119 of ribonuclease A is bound to the phosphate group in enzyme-nucleotide complexes [4]. This is now confirmed, since the apparent pK value of the phosphate group of these complexes is the same as the pK value of histidine.ll9 determined by proton magnetic resonance spectroscopy. Possible arrangements of the hydrogen bonds between the imidazole group of histidine-ll9 and the phosphate group are discussed. From linewidth broadening due to chemical exchange, an average life time of the complex of cytidine 2′-phosphate with ribonuclease A is derived. [ABSTRACT FROM AUTHOR]

Individual haemoglobin III from Chironomus thummi thummi is a monomeric protein (Mr = 15500) which has recently been shown by us to be characterized by a simple Bohr effect. Three of the four histidines, the position of which in the polypeptide chain is known from sequence analysis, are distinguished by their titration characteristics, namely His-G2, His-G19 and His-E5. rinse chemical shift of the C-2 proton resonances of the imidazole groups, which varies upon protonation of the histidine, has been used for the determination of the intrinsic pK values. His-F8, the proximally bound histidine, is not observable because its C-2 proton resonance is broadened. One of the three titratable histidines reveals a pK value which is varied in the range from 7.5 to 7.1, depending on the 6th ligand at the haem iron. The relatively high pK value of this histidine and its abnormal value of the chemical shift of the C-2 proton resonance at low pH indicate an interaction with a carboxylate group. This shift of the pK value caused by the binding of CO to reduced haemoglobin is in agreement with the interaction energy, calculated from the amplitude of the Bohr effect curve, and corresponds to 500 cal. In this simple case the assignment of the C-2 proton resonances to the known histidines is possible considering the atomic model, described by Huber et al. [4]. The results indicate that His-G2 is the allosteric binding site; the remaining two detectable histidines are not involved in the allosteric interaction. The molecular mechanism of the Bohr effect m this haemoglobin is discussed. [ABSTRACT FROM AUTHOR]