Niche Partitioning in Theropod Dinosaurs: Diet and Habitat Preference in Predators from the Uppermost Cedar Mountain Formation (Utah, U.S.A.).

We explore hypothetical ecologies to explain diversity among predatory dinosaurs in North America's medial Cretaceous, based on occurrence, tooth morphology, and stable isotope analysis. The Mussentuchit local fauna, Utah, USA, is among the best-known terrestrial vertebrate assemblages from the Cretaceous. Study samples include teeth from six microvertebrate sites, ranging in depositional setting from distal floodplain to channel lags. We recognize four theropod morphotypes: a comparatively large theropod (morph 1), a medium-sized dromaeosaurid (morph 2), a small dromaeosaurid (morph 3), and a tooth-morph similar to the genus Richardoestesia (morph 4). These four morphotypes vary significantly in mean size, from 15.1 mm in the largest theropod to 3.7 mm in Richardoestesia. Further, tooth representation from two of the best-sampled microsites (representing a channel/splay and floodplain deposit) show differing patterns of abundances with morphs 1 and 3 having roughly the same abundance in both sites, while morph 2 was more abundant in the floodplain setting and morph 4 was more abundant in the channel/splay. Stable isotope analysis (δ13C; δ18O) of tooth carbonate from the theropod morphotypes, goniopholidid crocodilians, and matrix (to test for diagenesis) from these sites were also analyzed. The theropods show modest differences in δ13C values between each other, with carbonate from the teeth of morphs 1, 3, and 4 being enriched in 13C for the channel/splay relative to the floodplain environments, possibly indicative of dietary plasticity in these species. We hypothesize that these data indicate that the Mussentuchit theropods had different niches within the predator guild, suggesting plausible means by which ecospace was divided among the predatory dinosaurs of the Mussentuchit local fauna.

Inhaled nitric oxide versus intravenous vasodilators in severe pulmonary hypertension after cardiac surgery.

UNLABELLED: Inhaled nitric oxide (iNO) is superior to i.v. vasodilators for treatment of pulmonary hypertension (PH) after cardiac surgery, but iNO is a potentially toxic gas, and patient subsets who benefit from iNO are not yet clearly defined. We administered iNO 40 ppm, prostaglandin E1 (PGE1) 0.1 microg x kg(-1) min(-1), and nitroglycerin (NTG) 3 to 5 microg x kg(-1) min(-1), in a randomized crossover study to 14 adult patients with severe PH after cardiac surgery. iNO, PGE1, and NTG were of similar efficacy in reducing pulmonary vascular resistance (P = 0.003). iNO induced selective pulmonary vasodilation, while PGE1 and NTG had significant concomitant systemic vasodilatory effects. iNO led to an increase in cardiac index (CI) (P = 0.012), and PGE1 increased CI (P = 0.006) and right ventricular (RV) ejection fraction (P = 0.015), while NTG had no effect on CI and RV performance. After study completion, patients continued with PGE1 administration with favorable in-hospital outcome. We conclude that PH per se, even if severe, does not necessarily imply postoperative RV dysfunction, and selective pulmonary vasodilation with iNO may not be superior to PGE1 with regard to CI and RV performance. IMPLICATIONS: In a prospective, randomized crossover study of inhaled nitric oxide (iNO) versus IV vasodilators, performed in adult patients with severe pulmonary hypertension but preserved right ventricular function after cardiac surgery, iNO was not superior to IV prostaglandin E1 with regard to cardiac index and right ventricular performance. Considering the potential toxicity of iNO, better definition of patient subsets with a positive benefit/risk ratio is warranted.

Documenting the diet in ancient human populations through stable isotope analysis of hair.

Fundamental to the understanding of human history is the ability to make interpretations based on artefacts and other remains which are used to gather information about an ancient population. Sequestered in the organic matrices of these remains can be information, for example, concerning incidence of disease, genetic defects and diet. Stable isotopic compositions, especially those made on isolates of collagen from bones, have been used to help suggest principal dietary components. A significant problem in the use of collagen is its long-term stability, and the possibility of isotopic alteration during early diagenesis, or through contaminating condensation reactions. In this study, we suggest that a commonly overlooked material, human hair, may represent an ideal material to be used in addressing human diets of ancient civilizations. Through the analysis of the amino-acid composition of modern hair, as well as samples that were subjected to radiation (thus simulating ageing of the hair) and hair from humans that is up to 5200 years old, we have observed little in the way of chemical change. The principal amino acids observed in all of these samples are essentially identical in relative abundances and content. Dominating the compositions are serine, glutamic acid, threonine, glycine and leucine, respectively accounting for approximately 15%, 17%, 10%, 8% and 8% of the total hydrolysable amino acids. Even minor components (for example, alanine, valine, isoleucine) show similar constancy between the samples of different ages. This constancy clearly indicates minimal alteration of the amino-acid composition of the hair. Further, it would indicate that hair is well preserved and is amenable to isotopic analysis as a tool for distinguishing sources of nutrition. Based on this observation, we have isotopically characterized modern individuals for whom the diet has been documented. Both stable nitrogen and carbon isotope compositions were assessed, and together provide an indication of trophic status, and principal type (C3 or C4) of vegetation consumed. True vegans have nitrogen isotope compositions of about 7/1000 whereas humans consuming larger amounts of meat, eggs, or milk are more enriched in the heavy nitrogen isotope. We have also analysed large cross-sections of modern humans from North America and Europe to provide an indication of the variability seen in a population (the supermarket diet). There is a wide diversity in both carbon and nitrogen isotope values based at least partially on the levels of seafood, corn-fed beef and grains in the diets. Following analysis of the ancient hair, we have observed similar trends in certain ancient populations. For example, the Coptics of Egypt (1000 BP) and Chinchorro of Chile (5000-800 BP) have diets of similar diversity to those observed in the modern group but were isotopically influenced by local nutritional sources. In other ancient hair (Egyptian Late Middle Kingdom mummies, ca. 4000 BP), we have observed a much more uniform isotopic signature, indicating a more constant diet. We have also recognized a primary vegetarian component in the diet of the Neolithic Ice Man of the Oetztaler Alps (5200 BP). In certain cases, it appears that sulphur isotopes may help to further constrain dietary interpretations, owing to the good preservation and sulphur content of hair. It appears that analysis of the often-overlooked hair in archaeological sites may represent a significant new approach for understanding ancient human communities.

The Ice Man's diet as reflected by the stable nitrogen and carbon isotopic composition of his hair.

Establishing the diets of ancient human populations is an integral component of most archaeological studies. Stable isotope analysis of well-preserved bone collagen is the most direct approach for a general assessment of paleodiet. However, this method has been limited by the scarcity of well-preserved skeletal materials for this type of destructive analysis. Hair is preserved in many burials, but is often overlooked as an alternative material for isotopic analysis. Here we report that the stable carbon and nitrogen isotope values for the hair of the 5200 year-old Ice Man indicates a primarily vegetarian diet, in agreement with his dental wear pattern. Whereas previous investigations have focused on bone collagen, the stable isotope composition of hair may prove to be a more reliable proxy for paleodiet reconstruction, particularly when skeletal remains are not well preserved and additional archaeological artifacts are unavailable.

New cyclic peptides from the ascidian Lissoclinum patella.

Four new cyclic peptides, patellamide G (2) and ulithiacyclamides E-G (3-5), along with the known patellamides A-C (6-8) and ulithiacyclamide B (9), were isolated from the ascidian Lissoclinum patella collected in Pohnpei, Federated States of Micronesia. The planar structures of these peptides were determined from 1D and 2D 1H and 13C NMR spectra. The absolute stereochemistries of the amino acid units, except for cysteine, were assigned by chiral GC analysis of N(O)-trifluoroacetyl isopropyl ester derivatives of amino acids obtained by acid hydrolysis of the intact and ozonized peptides. The structures of ulithiacyclamides E-G (3-5) were confirmed by chemical conversion. Patellamides B (7) and C (8) exhibited in vitro modulation of multidrug resistance in CEM/VBL100 cells.

Isotopic evidence for extraterrestrial non-racemic amino acids in the Murchison meteorite.

Many amino acids contain an asymmetric centre, occurring as laevorotatory, L, or dextrorotatory, D, compounds. It is generally assumed that abiotic synthesis of amino acids on the early Earth resulted in racemic mixtures (L- and D-enantiomers in equal abundance). But the origin of life required, owing to conformational constraints, the almost exclusive selection of either L- or D-enantiomers, and the question of why living systems on the Earth consist of L-enantiomers rather than D-enantiomers is unresolved. A substantial fraction of the organic compounds on the early Earth may have been derived from comet and meteorite impacts. It has been reported previously that amino acids in the Murchison meteorite exhibit an excess of L-enantiomers, raising the possibility that a similar excess was present in the initial inventory of organic compounds on the Earth. The stable carbon isotope compositions of individual amino acids in Murchison support an extraterrestrial origin -- rather than a terrestrial overprint of biological amino acids-although reservations have persisted. Here we show that individual amino-acid enantiomers from Murchison are enriched in 15N relative to their terrestrial counterparts, so confirming an extraterrestrial source for an L-enantiomer excess in the Solar System that may predate the origin of life on the Earth.

Stable nitrogen isotope analysis of amino Acid enantiomers by gas chromatography/combustion/isotope ratio mass spectrometry.

The analysis of the stable nitrogen isotope compositions of individual amino acid stereoisomers through the use of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) is presented. Nitrogen isotopic compositions of single amino acids or of their enantiomers is possible without the labor-intensive and time-consuming preparative-scale chromatographic procedures required for conventional stable isotope analysis. Following hydrolysis and derivatization, single-component isotope analysis is accomplished on nanomole quantities of each of the stereoisomers of an amino acid, utilizing the effluent stream of gas chromatographic separation. Nitrogen isotope fractionation is minimal during acylation of the amino acid, with no additional nitrogen being added stoichiometrically to the derivative. Thus, the isotopic composition of the nitrogen in the derivative is that of the original compound. Replicate stable nitrogen isotope analyses of 11 amino acids, and their trifluoroacetyl (TFA)/isopropyl (IP) ester derivatives, determined by both conventional isotope ratio mass spectrometry (IRMS) and GC/C/IRMS, indicate that the GC procedure is highly reproducible (standard deviations typically 0.3-0.4‰) and that isotopic differences between the amino acid and its TFA/IP derivative are, in general, less than 0.5‰.

Stable isotope analysis at the molecular level: a new approach for determining the origins of amino acids in the Murchison meteorite.

A combined gas chromatography/isotope ratio mass spectrometry (GC/IRMS) method has been developed that permits the direct stable carbon isotope analysis of N(O)-trifluoroacetyl-isopropyl esters of individual amino acids and their respective enantiomers at nanomole abundances. Calculation of the original delta 13C values of the amino acids is accomplished via a correction for the carbon introduced during the derivatization process. Previous GC/IRMS analyses of individual amino acids in the non-hydrolyzed water extract of an interior sample of a Murchison meteorite stone revealed an enrichment in 13C relative to terrestrial organic matter, in agreement with previous findings for bulk extracts. The range of amino acid delta 13C values (+5 to +30%, PDB) suggests possible kinetic effects during synthesis. In this study, an apparent kinetic isotope effect was also observed for the amino acid products of a spark discharge experiment. These preliminary results are supportive of a similar mechanism for the abiotic synthesis of amino acids in the Murchison meteorite.

Indigeneity of organic matter in fossils: a test using stable isotope analysis of amino acid enantiomers in Quaternary mollusk shells.

Comparison of the delta 13C values of D and L enantiomers of individual amino acids was used to evaluate the presence of amino acid contaminants in Quaternary land snails. Measurements of delta 13C values of amino acid D and L enantiomers determined by combined gas chromatography, combustion, isotope-ratio mass spectrometry are reported. Conventional combustion techniques, following separation of aspartic acid and glutamic acid enantiomers by liquid chromatography, were also used to determine delta 13C as well as delta 15N values. Thoroughly cleaned samples ranging in age from 7000 to > 100,000 yr B.P. are shown to have analytically identical delta 13C values for the D and L enantiomers of each amino acid, thus confirming that the amino acids are indigenous to the shells, even in Pleistocene samples. On the other hand, partially cleaned material shows divergence of isotopic values, thus indicating the presence of amino acid contaminants and emphasizing the importance of proper cleaning procedures. This approach provides a powerful method for assessing the indigeneity of amino acids in fossils.

Kinetics of peptide hydrolysis and amino acid decomposition at high temperature.

Dipeptide hydrolysis and amino acid decomposition appear to follow a first-order rate law. The hydrolysis rate increases exponentially with increasing temperature in aqueous solution at both 265 atm and water steam pressures over the temperature range of 100 to 220 degrees C. Dipeptide hydrolysis has a lower apparent activation energy at 265 atm (44.1 KJ/mol) than at water steam pressure (98.9 KJ/mol). At lower temperatures (<200-220 degrees C), the rate of peptide bond hydrolysis is faster at 265 atm than at water steam pressure. At higher temperatures (>200-220 degrees C), however, peptide bond hydrolysis is slower at 265 atm than at water steam pressure. In aqueous solution, amino acid decomposition rates also increase exponentially with increasing temperature. Amino acid decomposition rates are much higher at 265 atm than at water steam pressure over the entire temperature range investigated.

Carbon isotope composition of individual amino acids in the Murchison meteorite.

A significant portion of prebiotic organic matter on the early Earth may have been introduced by carbonaceous asteroids and comets. The distribution and stable-isotope composition of individual organic compounds in carbonaceous meteorites, which are thought to be derived from asteroidal parent bodies, may therefore provide important information concerning mechanistic pathways for prebiotic synthesis and the composition of organic matter on Earth before living systems developed. Previous studies have shown that meteorite amino acids are enriched in 13C relative to their terrestrial counterparts, but individual species were not distinguished. Here we report the 13C contents of individual amino acids in the Murchison meteorite. The amino acids are enriched in 13C, indicating an extraterrestrial origin. Alanine is not racemic, and the 13C enrichment of its D- and L-enantiomers implies that the excess of the L-enantiomer is indigenous rather than terrestrial contamination, suggesting that optically active materials were present in the early Solar System before life began.

4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.

alpha-Melanocyte-stimulating hormone (alpha-MSH) reversibly darkens frog skins by stimulating melanosome movement (dispersion) within melanophores. Heat-alkali treatment of alpha-MSH results in prolonged biological activity of the hormone. Quantitative gas chromatographic analysis of the hydrolyzed heat-alkali-treated peptide revealed partial racemization particularly at the 4(methionine) and 7(phenylalanine) positions. [Nle4]-alpha-MSH, a synthetic analogue of alpha-MSH, reversibly darkens frog skins and also exhibits prolonged activity after heat-alkali treatment. Synthesis of [Nle4, D-Phe7]-alpha-MSH provided an analogue with prolonged biological activity identical to that observed with heat-alkali-treated alpha-MSH or [Nle4]-alpha-MSH. [Nle4, D-Phe7]-alpha-MSH was resistant to enzymatic degradation by serum enzymes. In addition, this peptide exhibited dramatically increased biological activity as determined by frog skin bioassay, activation of mouse melanoma adenylate cyclase, and stimulation of mouse melanoma cell tyrosinase activity. This Nle4, D-Phe7 synthetic analogue of alpha-MSH is a very porent melanotropin, 26 times as potent as alpha-MSH in the adenylate cyclase assay. The resistance of the peptide to enzymatic degradation and its extraordinarily potent and prolonged biological activity should make this analogue of alpha-MSH an important molecular probe for studying the melanotropin receptors of both normal and abnormal (melanoma) melanocytes.