scholarly journals Energy-sparing adaptations in human pregnancy assessed by whole-body calorimetry

1989 ◽  
Vol 62 (1) ◽  
pp. 5-22 ◽  
Author(s):  
A. M. Prentice ◽  
G. R. Goldberg ◽  
H. L. Davies ◽  
P. R. Murgatroyd ◽  
W. Scott

The hypothesis that the energy cost of human pregnancy can be minimized by energy-sparing metabolic adaptations was tested using serial 24 h whole-body calorimetry. Eight healthy, well-nourished women were studied prepregnant and at 6, 12, 18, 24, 30 and 36 weeks gestation. Basal metabolic rate (BMR) showed highly characteristic changes within each subject and large inter-individual differences (F 3.5, P < 0.01). Some subjects showed a highly significant depression of metabolism up to 24 weeks gestation in support of the initial hypothesis. At 36 weeks BMR ranged from +8.6 to +35.4% relative to the prepregnant baseline. This wide variability was not explained by differences in the amount of lean tissue gained. Women displaying the energy-sparing suppression of BMR tended to be thin, suggesting that changes in metabolism may be responsive to initial energy status (ΔBMR ν. prepregnant body fat: r 0.84, P < 0.005). Changes in 24 h energy expenditure closely paralleled changes in BMR (r 0.98, P < 0.001), since the energy cost of minor voluntary activity and thermogenesis remained very constant within each individual. Pregnancy decreased the net cost of weight-dependent and weight-independent standard exercises when expressed per kg body-weight: stepping – 10 (sd 2)%, P < 0.001 at 18–36 weeks, cycling - 26 (sd 7)%, P < 0.01 at 12–36 weeks. The average integrated maintenance costs of pregnancy matched previous group estimates from well-nourished women, but individual estimates ranged from - 16 to + 276 MJ (coefficient of variation 93%). This high level of variability has important implications for the prescription of incremental energy intakes during pregnancy. It may also have had evolutionary significance.

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 557-564 ◽  
Author(s):  
Peter J. Quesenberry ◽  
Suju Zhong ◽  
Han Wang ◽  
Marc Stewart

Abstract We have previously shown that the keys to high-level nontoxic chimerism in syngeneic models are stem cell toxic, nonmyelotoxic host treatment as provided by 100-cGy whole-body irradiation and relatively high levels of marrow stem cells. This approach was unsuccessful in H-2 mismatched B6.SJL to BALB/c marrow transplants, but with tolerization, stable multilineage chimerism was obtained. Ten million B6.SJL spleen cells were infused intravenously into BALB/c hosts on day −10 and (MR-1) anti-CD40 ligand monoclonal antibody (mAb) injected intraperitoneally at varying levels on days −10, −7, −3, 0, and +3 and the BALB/c mice irradiated (100 cGy) and infused with 40 million B6.SJL/H-2 mismatched marrow cells on day 0. Stable multilineage chimerism at levels between 30% to 40% was achieved in the great majority of mice at 1.6 mg anti-CD40 ligand mAb per injection out to 64 weeks after transplantation, without graft-versus-host disease. The transplanted mice were also tolerant of donor B6.SJL, but not third-party CBA/J skin grafts at 8 to 9 and 39 to 43 weeks after marrow transplantation. These data provide a unique model for obtaining stable partial chimerism in H-2 mismatched mice, which can be applied to various clinical diseases of man such as sickle cell anemia, thalassemia, and autoimmune disorders.


1997 ◽  
Vol 38 (6) ◽  
pp. 1087-1093 ◽  
Author(s):  
R. Rossi Norrlund ◽  
D. Holback ◽  
L. Johansson ◽  
S.-O. Hietala ◽  
K. Riklund Åhlström

Purpose: Placental alkaline phosphatase (PLAP) is a membrane-bound oncofetal antigen that can be used for radioimmunotargeting. Preinjection of nonlabeled monoclonal anti-PLAP antibody (H7) and postinjection of monoclonal anti-idiotypic anti-PLAP antibody (αPH7) were used in order to improve the localization efficacy of 125I-labeled H7 Material and Methods: A human cervix adenocarcinoma cell line (HeLa Hep 2) was inoculated subcutaneously in 24 nude mice. Repeated quantitative radioimmunoscintigraphic recordings were performed on 27 occasions in each of the 24 mice during the observation period which lasted for nearly 3 months. the tumor and nontumor doses were calculated according to the Medical International Radiation Dose Committee formula on the basis of the scintigraphic data Results: All tumors were clearly visualized as early as one day after injection of 125I-labeled H7. the remaining radioactivity was exclusively located in the tumors at days 30–81. as much as 12–16% of the injected dose/g accumulated in the tumors during the first 2 days after injection, and remained stable at this high level for approximately 10 days in all investigated groups. Radioactivity in the whole body was rapidly eliminated during the same time period. the highest tumor/nontumor dose ratio was obtained after a single injection of 125I-labeled H7 Conclusion: Neither a preinjection of nonlabeled H7 nor a postinjection of αPH7 nor a combination of both strategies resulted in improved tumor/nontumor dose ratios compared to a single injection of labeled H7. the monoclonal antibody H7 has a rapid and high uptake, combined with a prolonged retention time in the tumors. the kinetic properties of H7 are different from antibodies targeting intracellular tumor antigens


1988 ◽  
Vol 91 (4) ◽  
pp. 765-768 ◽  
Author(s):  
Yosuke Aoyagi ◽  
Iwao Tasaki ◽  
Jun-ichi Okumura ◽  
Tatsuo Muramatsu

2021 ◽  
Author(s):  
Jason L. Pugh ◽  
Christopher P. Coplen ◽  
Alona S. Sukhina ◽  
Jennifer L. Uhrlaub ◽  
Jose Padilla-Torres ◽  
...  

ABSTRACTA popular “DNA-damage theory” of aging posits that unrepaired DNA damage leads to cellular (and organismal) senescence. Indeed, some hallmarks of immune aging are more prevalent in individuals exposed to Whole-Body Irradiation (WBI). To test this hypothesis in a model relevant to human immune aging, we examined separate and joint effects of lifelong latent Murine Cytomegalovirus (MCMV) and early-life WBI (i) over the course of the lifespan; (ii) in response to a West Nile virus (WNV) live attenuated vaccine; and (iii) following lethal WNV challenge subsequent to vaccination. We recently published that a single dose of non-lethal WBI in youth, on its own, was not sufficient to accelerate aging of the murine immune system despite causing widespread DNA damage and repopulation stress in hematopoietic cells. However, 4Gy sub-lethal WBI caused manifest reactivation of MCMV. Following vaccination and challenge with WNV in the old age, MCMV-infected animals experiencing 4Gy, but not lower, dose of sub-lethal WBI in youth had reduced survival. By contrast, old irradiated mice lacking MCMV and MCMV-infected, but not irradiated, mice were both protected to the same high level as the old non-irradiated, uninfected controls. Analysis of the quality and quantity of anti-WNV immunity showed that higher mortality in MCMV-positive WBI mice correlated with increased levels of MCMV-specific immune activation during WNV challenge. Moreover, we demonstrate that infection, including that by WNV, led to MCMV reactivation. Our data suggest that MCMV reactivation may be an important determinant of increased late-life mortality following early-life irradiation and late-life acute infection.


2019 ◽  
Author(s):  
Cody W. Whoolery ◽  
Sanghee Yun ◽  
Ryan P. Reynolds ◽  
Melanie J. Lucero ◽  
Ivan Soler ◽  
...  

ABSTRACTAstronauts on interplanetary space missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies with mature, “astronaut-aged” rodents show space radiation decreases performance in low- and some high-level cognitive tasks. Given the prevalence of touchscreens in astronaut training and in-mission assessment, and the ability of rodent touchscreen tasks to assess the functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, it is surprising the effect of space radiation on rodent touchscreen performance is unknown. To fill this knowledge gap, 6-month-old C57BL/6J male mice were exposed to whole-body space radiation and assessed on a touchscreen battery starting 1-month later. Relative to Sham, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation led to better performance on a dentate gyrus-reliant task of pattern separation ability. Irradiated mice discriminated similar visual cues in ∼40% fewer days and ∼40% more accurately than control mice. Improved pattern separation was not touchscreen-, radiation-particle, or neurogenesis-dependent, as both 56Fe and 28Si irradiation led to faster context discrimination (e.g. Sham Block 5 vs. 56Fe Block 2) in a non-touchscreen task and 56Fe led to fewer new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.SIGNIFICANCE STATEMENTAstronauts on an interplanetary mission - such as to Mars - will be unavoidably exposed to galactic cosmic radiation, a spectrum of highly-charged, fast-moving particles. Rodent studies suggest space radiation is detrimental to cognition. However, here we show this is not universally true. Mature mice that received whole body exposure to Mars-relevant space radiation perform similarly to control mice on high-level cognitive tasks, reflecting the functional integrity of key neural circuits. Even more surprisingly, irradiated mice perform better than controls in both appetitive and aversive tests of pattern separation, a mission-critical task reliant on dentate gyrus integrity. Notably, improved pattern separation was not touchscreen-, radiation-particle-, or neurogenesis-dependent. Our work urges revisitation of the generally-accepted conclusion that space radiation is detrimental to cognition.


2020 ◽  
Vol 34 (6) ◽  
pp. 8721-8733 ◽  
Author(s):  
Jennifer M. Rutkowsky ◽  
Trina A. Knotts ◽  
Paul D. Allen ◽  
Isaac N. Pessah ◽  
Jon J. Ramsey

1990 ◽  
Vol 68 (3) ◽  
pp. 482-492 ◽  
Author(s):  
D. A. McLennan ◽  
J. D. McPhail

Cladistic analysis of behavioural interactions during a series of female choice trials revealed three groups of reproductively unsuccessful males in a population of anadromous Gasterosteus aculeatus: inactive losers (losing male did not participate in choice test), active losers (losing male active during choice test), and fighting losers (subgroup of active losers defined by the observation that the female did not immediately follow the first male to approach her). The inactive losers group represents a "no choice" situation. In the remaining two groups, females responded preferentially to the most intensely coloured member of the competing male pair. This preferential response was strongest during the prechoice, captive presentation where the majority of females oriented head-up to, and tracked, the brighter red male. Once released, the female's initial response to the brighter courtship signal was overridden by the behavioural actions of the duller intensity male in 4 out of 12 trials. Although two of these males eventually lost the female to their rival, the remaining two individuals succeeded in spawning. Overall, 10 of 12 females spawned with the brighter red male. Given the brief breeding season and the advantage enjoyed by the most brightly coloured males in mate attraction, a high level of territorial intrusion is one way for an individual to attract a mate if he is surrounded by more intensely coloured neighbours.


Author(s):  
D. Grahame Hardie ◽  
A. Mark Evans

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that monitors the levels of AMP and ADP relative to ATP. If increases in AMP:ATP and/or ADP:ATP ratios are detected (indicating a reduction in cellular energy status), AMPK is activated by the canonical mechanism involving both allosteric activation and enhanced net phosphorylation at Thr172 on the catalytic subunit. Once activated, AMPK phosphorylates dozens of downstream targets, thus switching on catabolic pathways that generate ATP and switching off anabolic pathways and other energy-consuming processes. AMPK can also be activated by non-canonical mechanisms, triggered either by glucose starvation by a mechanism independent of changes in adenine nucleotides, or by increases in intracellular Ca2+ in response to hormones, mediated by the alternate upstream kinase CaMKK2. AMPK is expressed in almost all eukaryotic cells, including neurons, as heterotrimeric complexes comprising a catalytic α subunit and regulatory β and γ subunits. The α subunits contain the kinase domain and regulatory regions that interact with the other two subunits. The β subunits contain a domain that, with the small lobe of the kinase domain on the α subunit, forms the “ADaM” site that binds synthetic drugs that are potent allosteric activators of AMPK, while the γ subunits contain the binding sites for the classical regulatory nucleotides, AMP, ADP, and ATP. Although much undoubtedly remains to be discovered about the roles of AMPK in the nervous system, emerging evidence has confirmed the proposal that, in addition to its universal functions in regulating energy balance at the cellular level, AMPK also has cell- and circuit-specific roles at the whole-body level, particularly in energy homeostasis. These roles are mediated by phosphorylation of neural-specific targets such as ion channels, distinct from the targets by which AMPK regulates general, cell-autonomous energy balance. Examples of these cell- and circuit-specific functions discussed in this review include roles in the hypothalamus in balancing energy intake (feeding) and energy expenditure (thermogenesis), and its role in the brainstem, where it supports the hypoxic ventilatory response (breathing), increasing the supply of oxygen to the tissues during systemic hypoxia.


1987 ◽  
Vol 252 (5) ◽  
pp. E581-E587 ◽  
Author(s):  
M. M. Jepson ◽  
M. Cox ◽  
P. C. Bates ◽  
N. J. Rothwell ◽  
M. J. Stock ◽  
...  

Endotoxins induce muscle wasting in part as a result of depressed protein synthesis. To investigate whether these changes reflect impaired energy transduction, blood flow, O2 extraction, and high-energy phosphates in muscle and whole-body O2 consumption (VO2) have been measured. VO2 was measured for 6h after an initial sublethal dose of endotoxin (Escherichia coli lipopolysaccharide 0.3 mg/100 g body wt sc) or saline and during 6h after a second dose 24 h later. In fed or fasted rats, VO2 was either increased or better maintained after endotoxin. In anesthetized fed rats 3-4 after the second dose of endotoxin VO2 was increased, and this was accompanied by increased blood flow to liver (hepatic arterial supply), kidney, and perirenal brown adipose tissue and a 57 and 64% decrease in flow to back and hindlimb muscle, respectively, with no change in any other organ. Hindlimb arteriovenous O2 was unchanged, indicating markedly decreased aerobic metabolism in muscle, and the contribution of the hindlimb to whole-body VO2 decreased by 46%. Adenosine 5'-triphosphate levels in muscle were unchanged in endotoxin-treated rats, and this was confirmed by topical nuclear magnetic resonance spectroscopy, which also showed muscle pH to be unchanged. These results show that although there is decreased blood flow and aerobic oxidation in muscle, adenosine 5'-triphosphate availability does not appear to be compromised so that the endotoxin-induced muscle catabolism and decreased protein synthesis must reflex some other mechanism.


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