Search

PURPOSE: BRAF(V600E), a major driver of thyroid cancer, evaluated in the context of thyroid hormones and human relaxin. METHODS: Immunohistochemical expression of BRAF(V600E), TSH, TSH receptor (TSHR), T4, T3 receptor (T3R), RLNH2, and its receptor, RXFP1, were evaluated in thyroid tumors from a retrospective U.S. population of 481 cancer cases diagnosed in 1983-2004. RESULTS: BRAF(V600E) was expressed in 52% of all thyroid tumors; expression of other markers ranged from 25% for T4 to 98% for RLNH2. Tumors predominantly exhibited hypothyroid-like conditions characterized by elevated TSH and TSHR and reduced T4. BRAF(V600E) prevalence was significantly higher in tumors expressing TSH, TSHR, T3R, and RXFP1 and lower in tumors expressing T4. The proportion of BRAF(V600E) mutation in classic papillary tumors significantly increased from 56% to 72% over the 21-year period of diagnoses while expression of RXFP1, TSH, TSHR, and T3R decreased in non-tumor. Racial/ethnic differences were observed in thyroid hormone marker expression. Non-tumor expression of TSH, TSHR, and T3R were each associated with shorter overall survival but did not remain significant after adjustment for demographic and clinical factors. CONCLUSIONS: Our study provides the first evidence of the potential interaction of BRAF(V600E) mutation, relaxin, and thyroid hormones in thyroid carcinogenesis. Moreover, our results suggest that hypothyroidism, influenced by RLNH2 activity, may underlie the development of the majority of thyroid cancers and mediate the role of BRAF(V600E) in thyroid carcinogenesis. BRAF(V600E) mutation is increasing in papillary thyroid cancers and may be contributing to the rising incidence of this malignancy

This study was designed to show whether placental relaxin (RLN), its receptor (RXFP1), or insulin-like peptide 4 (INSL4) might have altered expression in patients with placenta accreta. The baseline expression of their genes through gestation (n = 34) was quantitated in the placental basal plate (BP) and villous trophoblast (TR), and compared to their expression in placenta accreta (n = 6). The proteins were also immunolocalized and quantitated in the accreta tissues. The messenger RNAs (mRNAs) of matrix metalloproteinase 9, -2, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were also measured. Results demonstrated that the BP and TR expressed low levels of RLN/RXFP1 and INSL4 through gestation. In accreta, increased RLN gene and protein in BP were associated with antepartum bleeding whereas INSL4 expression decreased throughout the TR. There were no changes in mRNAs for MMPs, but TIMP-1 was increased only in the invasive TR.

Size-related diet shifts are important characteristics of fish trophodynamics. Here, body size–related changes in muscle δ15N and δ13C of four coral reef fishes, Acanthurus nigrofuscus (herbivore), Chaetodon lunulatus (corallivore), Chromis xanthura (planktivore) and Plectropomus leopardus (piscivore) were investigated at two locations in the Solomon Islands. All four species occupied distinct isotopic niches and the concurrent δ13C′ values of C. xanthura and P. leopardus suggested a common planktonic production source. Size-related shifts in δ15N, and thus trophic level, were observed in C. xanthura, C. lunulatus and P. leopardus, and these trends varied between location, indicating spatial differences in trophic ecology. A literature review of tropical fishes revealed that positive δ15N-size trends are common while negative δ15N-size trends are rare. Size-δ15N trends fall into approximately equal groups representing size-based feeding within a food chain, and that associated with a basal resource shift and occurs in conjunction with changes in production source, indicated by δ13C. The review also revealed large scale differences in isotope-size trends and this, combined with small scale location differences noted earlier, highlights a high degree of plasticity in the reef fishes studied. This suggests that trophic size analysis of reef fishes would provide a productive avenue to identify species potentially vulnerable to reef impacts as a result of constrained trophic behaviour.

The human fetal membranes are complex tissues that perform many important functions during gestation. The extracellular matrix provides their strength to withstand the forces directed from the fetus and myometrium. Relaxin is a collagenolytic hormone that causes increased production of the matrix metalloproteinases. Its expression from the decidua is increased in patients with preterm premature rupture of the membranes, and its leucine-rich G receptor 7 is upregulated at preterm. The authors previously showed that relaxin is not involved in the infection-mediated cytokine response, but in the absence of infection, it causes increased secretion of both interleukin -6 and interleukin-8 from the membranes. In this article, the authors propose that relaxin is one of a number of sterile stimuli capable of causing increased proinflammatory cytokines, similar to but less robust than the effects of infection. These probably represent distinct inflammatory pathways involving different intracellular signaling events, which can result in either preterm premature rupture of the membranes or preterm labor. The current challenge is to fully understand these pathways and to clarify their similarities and differences.

Improved methods for selecting cultivars for their ability to grow well on low P soils will improve productivity and minimise pollution. Estimates are required of the relative values for different genotypes of physiologically meaningful parameters that define yield response to increasing levels of plant available soil P. The object of this study was to devise ways of obtaining these estimates from conventional trials that include numerous genotypes but only two P treatments. The parameters were estimated as coefficients of a modified Michaelis–Menten equation, namely A, the maximum yield that can be obtained with ample P, Km, the concentration of plant available P in the rooting medium at which yield is half the maximum, and B, the gradient of yield against available P as it approaches the origin. Two novel methods of estimation were devised. They both require inputs of yield and its variance at each of two concentrations of available P, but these must be within certain limits. Estimates of parameter values for 12 Brassica oleracea genotypes made by these methods from two P-levels in each of two experiments with six P levels were compared with the values obtained by conventional fitting to the data from all six P levels. According to regression and ranking analyses, the relative values of A obtained for the different genotypes by both two P-level methods were similar to those from the six P-level method and both were reproducible. None of the methods however detected any reproducible differences in Km. Application of one of the two P-level methods to published data for genotypes of other species indicated that there was little intra-species variation in Km within some data sets on maize, beans and leguminous cover crops but much within other data sets. Sensitivity and algebraic analyses are presented to define the experimental conditions required for successful use of two P-level methods. It is concluded that, provided these experimental conditions are met, measurements at two P levels can give almost as much information about intra-species differences in P response parameters as measurements at six P levels. The procedure may also be useful for interpreting other responses of a “diminishing returns” type such as those to other nutrients or plant spacing.

The absence of any torsional fatigue-test data on currently used titanium-alloy spring wire along with inconsistent fatigue-test data derived from earlier test programs prompted this investigation. The torsional fatigue testing was performed on straight lengths of 13V−11Cr−3Al titanium-alloy spring wire in diameters of 0.148 in. (0.376 cm), 0.225 in. (0.572 cm) and 0.374 in. (0.950 cm) considered as representative. A second material selected as a possible alternate for 13V−11Cr−3Al spring was 3Al−8V−6Cr−4Mo−4Zr which was tested in diameters of 0.225 in. (0.572 cm) and 0.376 in. (0.955 cm). Testing as straight-wire lengths eliminated the manufacturing variables introduced by fabricating a helical-spring geometry. Two methods were considered for improving fatigue life, namely abrasive cleaning and shot peening. At a torsional stress of 100 ksi (689.5 MPa), the test data indicate that an improvement in fatigue life of at least one order of magnitude may be realized by shot peening 0.225-in. (0.572-cm)-diam 13V−11Cr−3Al wire to an intensity of 0.015A. A similar improvement of fatigue life may be gained by shot peening 0.148-in. (0.376-cm)-diam wire to a similar intensity. A substantial fatigue-life improvement was obtained by an obrasive-cleaning operation on all wire diameters tested. The fatigue life of the 3Al−8V−6Cr−4Mo−4Zr titanium-alloy wire in the cold-worked and aged condition was lower at all stress levels and diameters tested than for similar diameters of 13V−11Cr−3Al titanium-alloy wire.

A recently formulated concept of stochastic localizability is shown to be consistent with a concept of stochastic microcausality, which avoids the conclusions of Hegerfeldt's no-go theorem as to the inconsistency of sharp localizability of quantum particles and Einstein causality. The proposed localizability on quantum space-time is shown to lead to strict asymptotic causality. For finite time evolutions, upper bounds on propagation to the exterior of stochastic light cones are derived which show that the resulting probabilities are too small to be actually observable in a realistic context.

THE sequence of the ovarian peptide, relaxin, has recently been reported1,2 and the observation1 that it can be accommodated into the insulin fold has been discussed3,4. Only 11 residues, including the cystines, are common to insulin and relaxin (Fig. 1), but the probable identity of the cystine pairings and the preservation of the hydrophobic character of buried residues suggests some structural homology between the two hormones. The extent of sequence changes and the remote relationship between the corpus luteum and the pancreas, the respective sources of relaxin and insulin, makes homology of the two hormones most interesting. We have therefore rigorously examined the relaxin conformation by a computer graphics system and found it possible to accommodate the relaxin sequence within the insulin main-chain geometry.

Cereal yield per ha in the different countries of the world is almost proportional to the rate of fertilizer application. Yields in countries where most people live are severely limited by nutrient deficiencies. Unless steps are taken to rectify these deficiencies, crop yields will always be very poor, even if other improved agronomic practices are adopted.

In 1967 the nine Imperial Smelting Furnaces in operation produced 352,000 tons of zinc and 185,000 tons of lead. By 1970, when the four now under construction also come into operation, the annual production should be at the rate of zinc 800,000 tons, lead 450,000 tons. It can, therefore, be claimed that although the process is primarily for the production of zinc, it is also an important producer of lead.

The technique of immunosympathectomy was used to investigate the relative importance of sympathetically mediated processes in the body temperature responses of mice to reserpine treatment and the thermogenic effects of subsequently administered anti-depressant and CNS stimulant drugs. It was found that immunosympathectomized mice were less sensitive to the temperature lowering effects of reserpine but exhibited, unexpectedly, an enhanced thermogenic response to each of the representative antidepressant and stimulant drugs tested. These findings appear to exclude the sympathetic division of the autonomic nervous system as an essential prerequisite for the thermogenic effects of anti-depressant and stimulant drugs in reserpine treated mice. It is suggested that the observed effects could be accounted for in terms of a possible hyperfunctional adrenal gland.

1. Anaerobic amino-acid breakdown in a garden soil was accompanied by the formation of large quantities of volatile fatty acid and ammonia (plus indole in the case of tryptophan).

HISAW and co-workers1,2 first described a factor from sow corpora lutea that caused relaxation of the pubic symphysis in oestrogen-primed guinea pigs. Subsequent studies have shown that the active substance, termed relaxin, is a low molecular weight peptide hormone. Its presence has been demonstrated during pregnancy in female pigs, guinea pigs, rabbits, mice and rats3,4, and, more recently, in humans5. Its actions include dilatation and softening of the cervix, inhibition of uterine contractions and relaxation of the pubic symphysis and other pelvic joints. Relaxin, which has a molecular weight of approximately 6,000, consists of two non-identical chains joined by disulphide bridges6. We have now determined, and report here, the complete amino acid sequence of porcine relaxin.

26-Hydroxy-β-ecdysone has been identified as a metabolite of the moulting hormone, β-ecdysone inCalliphora erythrocephala.

Theoretical Solid State Physics. By Albert Haug. Vol. 1. Pp. xiv + 497. (Pergamon: Oxford and New York, May 1972.) £7. Theoretical Solid State Physics. By Albert Haug. Translated by H. S. H. Massey. Edited by D. ter Haar. Vol. 2. Pp. xiii + 355. (Pergamon: Oxford and New York, August 1972.) £6.