scholarly journals The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways

2021 ◽  
Vol 118 (31) ◽  
pp. e2101977118
Author(s):  
Libia Alejandra García-Flores ◽  
Cara L. Green ◽  
Sharon E. Mitchell ◽  
Daniel E. L. Promislow ◽  
David Lusseau ◽  
...  

The evolutionary context of why caloric restriction (CR) activates physiological mechanisms that slow the process of aging remains unclear. The main goal of this analysis was to identify, using metabolomics, the common pathways that are modulated across multiple tissues (brown adipose tissue, liver, plasma, and brain) to evaluate two alternative evolutionary models: the “disposable soma” and “clean cupboards” ideas. Across the four tissues, we identified more than 10,000 different metabolic features. CR altered the metabolome in a graded fashion. More restriction led to more changes. Most changes, however, were tissue specific, and in some cases, metabolites changed in opposite directions in different tissues. Only 38 common metabolic features responded to restriction in the same way across all four tissues. Fifty percent of the common altered metabolites were carboxylic acids and derivatives, as well as lipids and lipid-like molecules. The top five modulated canonical pathways were l-carnitine biosynthesis, NAD (nicotinamide adenine dinucleotide) biosynthesis from 2-amino-3-carboxymuconate semialdehyde, S-methyl-5′-thioadenosine degradation II, NAD biosynthesis II (from tryptophan), and transfer RNA (tRNA) charging. Although some pathways were modulated in common across tissues, none of these reflected somatic protection, and each tissue invoked its own idiosyncratic modulation of pathways to cope with the reduction in incoming energy. Consequently, this study provides greater support for the clean cupboards hypothesis than the disposable soma interpretation.

2007 ◽  
Vol 35 (4) ◽  
pp. 647-651 ◽  
Author(s):  
G.J. Laurent ◽  
R.C. Chambers ◽  
M.R. Hill ◽  
R.J. McAnulty

Fibroblasts are multifunctional cells that are responsible for matrix homoeostasis, continuously synthesizing and degrading a diverse group of extracellular molecules and their receptors. Rates of turnover of matrix molecules and the proteases that degrade them are normally under the control of diverse chemical and mechanical cues, with cytokines, growth factors, proteases, lipid mediators and mechanical forces playing roles. The maintenance of this homoeostasis is vital to the preservation of normal tissue function and is clearly lost in chronic diseases of the joints, skin and internal organs where destruction and excessive deposition is seen. Current research is focusing on defining the key pathways of activation either in resident fibroblasts, matrix-producing cells derived from circulating fibrocytes, or from transdifferentiation of resident cells. The common downstream signalling pathways are also being defined, as well as the gene interactions leading to altered cell phenotype. The present article reviews these findings and our current concepts of the key molecular events leading to tissue damage and excessive matrix deposition in tissue fibrosis. These studies are leading to an appreciation of the complexity of events with multiple pathways involved, but, as the facts emerge, we are finding promising new ways to treat fibrosis and halt the inexorable progression that is a feature of so many fibrotic and remodelling disorders.


2019 ◽  
pp. 13-38
Author(s):  
Nathan Lyons

Part I of this book sets out a semiotic theory of human culture. This chapter uses the semiotics of John Poinsot (1589–1644, also known as John of St Thomas) to show how the whole scope of human cultural activity can be understood as at root the work of signs. Poinsot has a very wide-ranging understanding of signification, which includes natural, customary, and stipulated signs; physical and formal/psychological signs; and perceptual and communicative signs. Crucially, a single metaphysics of relations is the common basis for this whole spectrum of signs, so that natural and cultural signs count univocally as instances of signification. Poinsot’s notion of semiotic custom, in which conventional signs are ‘naturalised’ through habit to act as natural signs, is an important theme (to which chapters 5 and 6 will return in an evolutionary context). Poinsot’s semiotics illuminates the full anthropological ‘breadth’ of culture.


2014 ◽  
Vol 281 (1795) ◽  
pp. 20141177 ◽  
Author(s):  
Esa-Ville Immonen ◽  
Irina Ignatova ◽  
Anna Gislen ◽  
Eric Warrant ◽  
Mikko Vähäsöyrinki ◽  
...  

The common backswimmer, Notonecta glauca , uses vision by day and night for functions such as underwater prey animal capture and flight in search of new habitats. Although previous studies have identified some of the physiological mechanisms facilitating such flexibility in the animal's vision, neither the biophysics of Notonecta photoreceptors nor possible cellular adaptations are known. Here, we studied Notonecta photoreceptors using patch-clamp and intracellular recording methods. Photoreceptor size (approximated by capacitance) was positively correlated with absolute sensitivity and acceptance angles. Information rate measurements indicated that large and more sensitive photoreceptors performed better than small ones. Our results suggest that backswimmers are adapted for vision in both dim and well-illuminated environments by having open-rhabdom eyes with large intrinsic variation in absolute sensitivity among photoreceptors, exceeding those found in purely diurnal or nocturnal species. Both electrophysiology and microscopic analysis of retinal structure suggest two retinal subsystems: the largest peripheral photoreceptors provide vision in dim light and the smaller peripheral and central photoreceptors function primarily in sunlight, with light-dependent pigment screening further contributing to adaptation in this system by dynamically recruiting photoreceptors with varying sensitivity into the operational pool.


1997 ◽  
Vol 273 (2) ◽  
pp. R784-R789 ◽  
Author(s):  
A. A. Romanovsky ◽  
V. A. Kulchitsky ◽  
C. T. Simons ◽  
N. Sugimoto ◽  
M. Szekely

Subdiaphragmatically vagotomized rats cannot mount a febrile response to pyrogens and are believed to have severe thermoregulatory deficiencies. We addressed the issue of thermoeffector competence of vagotomized rats by asking three questions. In Expt. 1 we asked, can vagotomized rats readily recruit tail skin vasoconstriction in the course of a moderate cold exposure? In Expt. 2 the question was, can brown adipose tissue (BAT) thermogenesis readily be activated in vagotomized rats (e.g., in response to a tail pinch)? In Expt. 3, we investigated the question: can vagotomized rats elevate their body temperature in response to ephedrine (a drug of high hyperthermizing potential) to the same extent as sham-operated controls? Rats were vagotomized or sham operated and implanted with a catheter into the jugular vein and a thermocouple into the interscapular BAT. To prevent the common complications of vagotomy, special perioperative care was given. During experiments, colonic, tail skin, and BAT temperatures (Tc, Tsk, and TBAT, respectively) were measured. The vagotomized animals were well nourished and had a body mass (325 +/- 6 g) similar to that of the controls (338 +/- 6 g). In Expt. 1, in response to external cooling (15 degrees C, 1 h), the vagotomized (n = 30) and sham-operated (n = 31) rats recruited tail skin vasoconstriction at close values of both Tc (37.84 +/- 0.08 and 37.97 +/- 0.07 degrees C) and Tsk (33.16 +/- 0.17 and 33.18 +/- 0.18 degrees C, respectively). In Expt. 2, tail pinch-associated stress in vagotomized rats resulted in a sharp rise in the TBAT-Tc gradient by 0.3-1.0 degree C. In Expt. 3, ephedrine administered intravenously (whether in a 5 or 35 mg/kg dose) evoked similar hyperthermic responses in the vagotomized and sham-operated rats: a moderate (approximately 2.5 degrees C) Tc rise in the low dose and a "supramaximal" (approximately 5.0 degrees C) rise in the high dose. In sum, the answer to all three questions asked is yes. Vagotomized rats, at least when well nourished, exhibit no signs of thermoeffector deficiency. It is, therefore, not effector incompetence but rather vagal deafferentation per se that can explain the febrile irresponsiveness of vagotomized rats.


Author(s):  
Marc W. Cadotte ◽  
T. Jonathan Davies

This chapter examines a variety of methods for detecting the patterns of evolution of a certain trait. It first considers common metrics for evaluating phylogenetic signal and compares fit of alternative evolutionary models. When trait data deviates significantly from assumptions of Brownian motion (BM), the phylogenetic distances separating taxa on a time-calibrated tree might not accurately capture phenotypic distance between species. If we are able to identify the correct model of trait evolution, we can transform the branch lengths on the phylogenetic tree to match. Nevertheless, we might still favor using the untransformed tree because complex evolutionary models might not generalize across traits. The chapter also reviews alternative models of trait evolution, including a model of constrained evolution, multirate and multioptima models, speciational models, and white noise model. Finally, it looks at some of the common models for reconstructing ancestral states for discrete and continuous data.


1953 ◽  
Vol 99 (416) ◽  
pp. 357-373 ◽  
Author(s):  
E. Gellhorn

The present investigation belongs to a series of studies (1) in which an attempt has been made to contribute to an understanding of the mechanisms underlying those forms of therapy of mental diseases which directly involve physiological mechanisms.† In the previous work an experimental analysis was performed in order to determine the common factor involved in the various forms of so-called shock therapy. It was found that all forms of this therapy produced in the experimental animal an increased reactivity of the centres of the sympathetic system to direct (2) and reflex stimulation (3). Chronic experiments (4) also showed that these alterations in autonomic reactivity persisted for a long period of time if the “therapy” (e.g., electroshock) was applied repeatedly as it is commonly done in the human patient. Special experiments revealed that increased sympathetic reactivity can be demonstrated in the hypothalamus (5).


2011 ◽  
Vol 63 (4) ◽  
pp. 915-920
Author(s):  
Ljiljana Rakicevic ◽  
Natasa Petrovic ◽  
Dragica Radojkovic ◽  
Snezana Kojic

MARP family members CARP, Ankrd2 and DARP are expressed in the striated muscle, while DARP protein is also detected in brown adipose tissue (BAT). Taking into account recent findings concerning the common origin of muscle and brown fat, expression of CARP and Ankrd2 in mouse BAT was investigated. We demonstrated Ankrd2 expression in both inactive and thermogenically active BAT, while CARP expression was not detected. Our findings suggest that the expression of Ankrd2 in BAT could be a part of the ?myogenic transcriptional signature?, further supporting the evidence that muscle and brown adipose cells arise from the same myoblastic precursor.


1993 ◽  
Vol 71 (3) ◽  
pp. 544-549 ◽  
Author(s):  
Gregory J. Robertson ◽  
Fred Cooke

Intraclutch egg-size variation and hatching success were studied in a population of Hudson Bay common eiders (Somateria mollissima sedentaria) at La Pérouse Bay, Manitoba (58°24′N, 94°24′W), to test the hypothesis that females allocate more nutrient reserves to eggs that are more likely to hatch. Egg volumes were calculated for 575 known-sequence eggs in 134 complete clutches of 3–6 eggs. In general, the length of eggs decreased linearly with position in the laying sequence, whereas the breadth of eggs followed a curvilinear pattern, the second or third egg being the widest. For all clutch sizes, the last-laid egg was the smallest and the second- or third-laid egg the largest. Hatching success also varied with position in the laying sequence. Pre-incubation failure declined over the laying sequence, whereas hatching failure (dead, infertile, or rotten eggs) increased. In all cases pre-incubation failure was the major cause of egg loss (84% of total loss). Overall, third and fourth eggs were the most successful and first eggs were the least successful. With one exception, successful and unsuccessful eggs were the same size within a laying sequence. We conclude that there is no clear relationship between egg size and hatching success, and that laying sequence per se has a greater effect on hatching success. Female eiders do not appear to allocate more reserves to eggs that are most likely to hatch, and we consider other proximate, physiological mechanisms to explain the observed pattern of intraclutch egg-size variation.


Author(s):  
A. Louise Allcock ◽  
Phillip C. Watts ◽  
John P. Thorpe

In the common intertidal sea anemone Actinia equina (Cnidaria: Actiniaria) the morphological plasticity and lack of hard parts has caused considerable debate as to what constitutes a species. Over the last several years genetic studies have indicated that this ‘species’ consists of various separate gene-pools which appear to function as cryptic biological species. Conventional taxonomy has often concentrated on the use of a cnidome, the type, structure and number of nematocysts ('stinging’ cells). However, the usefulness of nematocysts to distinguish among various morphs of A. equina and other anthozoan species has recently been questioned. Here we describe the first detailed study of nematocyst differences between two well characterized genetically differentiated morphs with different coloured pedal discs. Measurements were taken from each type of nematocyst in five different tissues. Contrary to expectations, clear and significant nematocyst differences were found between Actinia with red or pink pedal discs and others with green to grey pedal discs. These findings support previous electrophoretic studies and suggest that quantitative descriptions of the cnidome may accurately identify separate species within other genera of Anthozoa.


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