Carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) stable isotope ratios were longitudinally measured in fingernail and hair samples from mother-infant pairs where infants were exclusively breastfed (n = 5), breast- and formula-fed (n = 2), or exclusively formula-fed (n = 1) from birth. All exclusively breastfed infants had a dual enrichment in carbon ( approximately 1 per thousand) and nitrogen ( approximately 2-3 per thousand) when compared to maternal values. In contrast, breast- and formula-fed subjects had reduced enrichments compared to exclusively breastfed subjects, and the exclusively formula-fed infant showed no increase in delta(13)C or delta(15)N values. This finding of a carbon trophic level effect in breastfeeding infants suggests that (13)C-enrichments of approximately 1 per thousand in archaeological populations are not necessarily the result of the consumption of C(4)-based weaning foods such as maize or millet. During the weaning process, the delta(13)C results for breastfed infants declined to maternal levels more rapidly than the delta(15)N results. This suggests that delta(13)C values have the potential to track the introduction of solid foods into the diet, whereas delta(15)N values monitor the length of time of breast milk consumption. These findings can be used to refine the isotopic analysis of breastfeeding and weaning patterns in past and modern populations.

While past experiments on animals, birds, fish, and insects have shown changes in stable isotope ratios due to nutritional stress, there has been little research on this topic in humans. To address this issue, a small pilot study was conducted. Hair samples from eight pregnant women who experienced nutritional stress associated with the nausea and vomiting of morning sickness (hyperemesis gravidarum) were measured for carbon (delta13C) and nitrogen (delta15N) stable isotope ratios. The delta13C results showed no change during morning sickness or pregnancy when compared with pre-pregnancy values. In contrast, the delta15N values generally increased during periods of weight loss and/or restricted weight gain associated with morning sickness. With weight gain and recovery from nutritional stress, the hair delta15N values displayed a decreasing trend over the course of gestation towards birth. This study illustrates how delta15N values are not only affected by diet, but also by the nitrogen balance of an individual. Potential applications of this research include the development of diagnostic techniques for tracking eating disorders, disease states, and nitrogen balance in archaeological, medical, and forensic cases.

Carbon (13C/12C) and nitrogen (15N/14N) stable isotope ratios were longitudinally measured in human hair that reflected the period from pre-conception to delivery in 10 pregnant women. There was no significant change in the delta13C results, but all subjects showed a decrease in delta15N values (-0.3 to -1.1 per thousand) during gestation. The mechanisms causing this decrease in hair delta15N have not been fully elucidated. However, since the delta15N values of dietary nitrogen and urea nitrogen are significantly lower compared to maternal tissues, it is hypothesized that the increased utilization of dietary and urea nitrogen for tissue synthesis during pregnancy resulted in a reduction of the steady state diet to a body trophic level effect by approximately 0.5-1 per thousand. An inverse correlation (R2 = 0.67) between hair delta15N and weight gain was also found, suggesting that positive nitrogen balance results in a reduction of delta15N values independent of diet. These results indicate that delta15N measurements have the ability to monitor not only dietary inputs, but also the nitrogen balance of an organism. A potential application of this technique is the detection of fertility patterns in modern and ancient species that have tissues that linearly record stable isotope ratios through time.

The maintenance of a constant ATP level ('set-point') is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of ATP homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes), recently discovered dynamic activity of mitochondria, play an essential role for the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes negatively regulate ATP production in isolated respiring mitochondria and, their activity waxes and wanes to counteract the ATP supply-demand imbalance caused by superfluous substrate and altered workload in cardiomyocytes. Moreover, manipulating mitoflash activity is sufficient to inversely shift the otherwise stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage through F 1 F o-ATP synthase appears to mediate the coupling between mitoflash production and ATP set-point regulation. These findings indicate mitoflashes appear to constitute a digital auto-regulator for ATP homeostasis in the heart.

Heart tissue is remarkably sensitive to oxygen deprivation. Although heart cells, like those of most tissues, rapidly adapt to anoxic conditions, relatively short periods of ischaemia and subsequent reperfusion lead to extensive tissue death during cardiac infarction. Heart tissue is not readily regenerated, and permanent heart damage is the result. Although mitochondria maintain normal heart function by providing virtually all of the heart's ATP, they are also implicated in the development of ischaemic damage. While mitochondria do provide some mechanisms that protect against ischaemic damage (such as an endogenous inhibitor of the F1Fo-ATPase and antioxidant enzymes), they also possess a range of elements that exacerbate it, including ROS (reactive oxygen species) generators, the mitochondrial permeability transition pore, and their ability to release apoptotic factors. This review considers the process of ischaemic damage from a mitochondrial viewpoint. It considers ischaemic changes in the inner membrane complexes I-V, and how this might affect formation of ROS and high-energy phosphate production/degradation. We discuss the contribution of various mitochondrial cation channels to ionic imbalances which seem to be a major cause of reperfusion injury. The different roles of the H+, Ca2+ and the various K+ channel transporters are considered, particularly the K+(ATP) (ATP-dependent K+) channels. A possible role for the mitochondrial permeability transition pore in ischaemic damage is assessed. Finally, we summarize the metabolic and pharmacological interventions that have been used to alleviate the effects of ischaemic injury, highlighting the value of these or related interventions in possible therapeutics.

Historical documents indicate that breastfeeding and weaning practices have fluctuated in England through history. In order to obtain evidence for general breastfeeding patterns in Late/Sub-Roman Britain, stable carbon and nitrogen isotope values were measured in juvenile and adult skeletons (n = 87) from the cemetery of Queenford Farm, Dorchester-on-Thames, Oxfordshire. As the site contained few individuals between 0-1.5 years of age, it was not possible to determine the initial timing for the introduction of weaning foods. Between ages 2-4 years, the mean +/- SD delta(13)C results (-20.2 +/- 0.3 per thousand) are significantly more negative (t = -4.03, P < 0.001) compared to adult females (-19.7 +/- 0.3 per thousand). This is interpreted as evidence of a different diet being fed to children during weaning. After age 2, the delta(15)N values gradually decline, indicating complete cessation of breastfeeding by 3-4 years. Among adults, stature (males = 1.68 +/- 0.06 m; females = 1.58 +/- 0.07 m) and sexual dimorphism (106) were low, suggesting that the population was possibly under environmental stress. The delta(13)C results for adults are similar, but females show a small but statistically significantly (t = -2.86, P < 0.01) lower mean delta(15)N value (9.9 +/- 0.9 per thousand) compared to males (10.6 +/- 0.5 per thousand). These lower female delta(15)N values possibly reflect the different physiology of the sexes (pregnancy and/or lactation) or the reduced consumption of animal/fish protein by women, and this may have been influenced by individual preference, family needs, or societal values of the era.

Subarachnoid haemorrhage is often followed by haemolysis and concomitant oxidative stress, and is frequently complicated by pathological vasoconstriction or cerebral vasospasm. It is known that upregulation of haem oxygenase (HO-1) is induced by oxidative stress and results in release of biliverdin and bilirubin (BR), which are scavengers of reactive oxygen species (ROS). Here we report biomimetic studies aimed at modelling pathological conditions leading to oxidative degradation of BR. Oxidative degradation products of BR, formed by reaction with hydrogen peroxide (an ROS model system), demonstrated biological activity by stimulating oxygen consumption and force development in vascular smooth muscle from porcine carotid artery. Analogous biological activity was observed with vasoactive cerebrospinal fluid from subarachnoid haemorrhage patients. Three degradation products of BR were isolated: two were assigned as isomeric monopyrrole (C 9 H 11 N 2 O 2 ) derivatives, 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide and 3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide and the third was 4-methyl-3-vinylmaleimide (MVM), a previously isolated photodegradation product of biliverdin. Possible mechanisms of oxidative degradation of BR are discussed. Tentative assignment of these structures in the cerebrospinal fluid (CSF) of cerebral vasospasm patients has been made. It is proposed that one or more of the degradation products of biliverdin or bilirubin are involved in complications such as vasospasm and or pathological vasoconstriction associated with haemorrhage.

2 See infra notes 15 through 19 and accompanying text. To legally stop a person, a police officer must have at least reasonable suspicion of criminal activity. Terry v. Ohio, 392 U.S. 1 (1968). S Brief for the United States at 5-6, United States v. Whren, 116 S. Ct. 1769 (1996) (No. 95-5841). 4 Whren, 116 S. Ct. at 1773 (defendant petitioners asked that the standard be "whether a police officer, acting reasonably, would have made the stop for the reason given" (emphasis added)).