Metabolomics of aging assessed in individual parasitoid wasps

Metabolomics studies of low-biomass organisms, such as small insects, have previously relied on the pooling of biological samples to overcome detection limits, particularly using NMR. We show that the differentiation of metabolite profiles of individual 1 mg parasitoid wasps of different ages is possible when using a modified sample preparation and a combination of untargeted NMR and LC-MS based metabolomics. Changes were observed between newly emerged and older wasps in glycerolipids, amino acids and circulatory sugars. This advance in chemical profiling has important implications for the study of the behaviour and ecology of parasitoids and many other species of small organisms because predictions and observations are typically made at the level of the individual. Thus, the metabolomic state of low-biomass individuals can now be related to their behaviour and ecological performance. We discuss specifically the utility of age-related metabolomic profiling but our new approach can be applied to a wide range of biological research

Toward a New Philosophy of Preventive Nutrition: From a Reductionist to a Holistic Paradigm to Improve Nutritional Recommendations

The reductionist approach has been predominant to date in human nutrition research and has unraveled some of the fundamental mechanisms at the basis of food nutrients (e.g., those that involve deficiency diseases). In Western countries, along with progress in medicine and pharmacology, the reductionist approach helped to increase life expectancy. However, despite 40 y of research in nutrition, epidemics of obesity and diabetes are growing each year worldwide, both in developed and developing countries, leading to a decrease in healthy life years. Yet, interactions between nutrition-health relations cannot be modeled on the basis of a linear cause-effect relation between 1 food compound and 1 physiologic effect but rather from multicausal nonlinear relations. In other words, explaining the whole from the specific by a bottom-up reductionist approach has its limits. A top-down approach becomes necessary to investigate complex issues through a holistic view before addressing any specific question to explain the whole. However, it appears that both approaches are necessary and mutually reinforcing. In this review, Eastern and Western research perspectives are first presented, laying out bases for what could be the consequences of applying a reductionist versus holistic approach to research in nutrition vis-a-vis public health, environmental sustainability, breeding, biodiversity, food science and processing, and physiology for improving nutritional recommendations. Therefore, research that replaces reductionism with a more holistic approach will reveal global and efficient solutions to the problems encountered from the field to the plate. Preventive human nutrition can no longer be considered as "pharmacology" or foods as "drugs.

Microbial−mammalian cometabolites dominate the age-associated urinary metabolic phenotype in Taiwanese and American populations

Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. 1H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n = 857; age 54–91 years) and the Mid-Life in the USA study (MIDUS II; n = 1148; age 35–86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites—4-cresyl sulfate (4CS) and phenylacetylglutamine (PAG)—were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p < 4 × 10–6). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultraperformance liquid chromatography–mass spectrometry (UPLC–MS). Both are products of concerted microbial–mammalian host cometabolism and indicate an age-related association with the balance of host–microbiome metabolism

Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts

Aging is a major risk factor for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). As metabolic alterations are a hallmark of aging and have previously been observed in ALS, it is important to examine the effect of aging in the context of ALS metabolic function. Here, using a newly established phenotypic metabolic approach, we examined the effect of aging on the metabolic profile of fibroblasts derived from ALS cases compared to controls. We found that ALS fibroblasts have an altered metabolic profile, which is influenced by age. In control cases, we found significant increases with age in NADH metabolism in the presence of several metabolites including lactic acid, trehalose, uridine and fructose, which was not recapitulated in ALS cases. Conversely, we found a reduction of NADH metabolism with age of biopsy, age of onset and age of death in the presence of glycogen in the ALS cohort. Furthermore, we found that NADH production correlated with disease progression rates in relation to a number of metabolites including inosine and α-ketoglutaric acid. Inosine or α-ketoglutaric acid supplementation in ALS fibroblasts was bioenergetically favourable. Overall, we found aging related defects in energy substrates that feed carbon into glycolysis at various points as well as the tricarboxylic acid (TCA) cycle in ALS fibroblasts, which was validated in induced neuronal progenitor cell derived iAstrocytes. Our results suggest that supplementing those pathways may protect against age related metabolic dysfunction in ALS

Synthesis, characterization, redox kinetics, and assessment of DNA and thiol binding of a new class of platinum(II) and -(IV) pyrophosphato complexes

Includes bibliographical references (pages 142-148)A series of mononuclear platinum(II) pyrophosphato complexes was synthesized and characterized by x-ray crystallography and phosphorous-31 and platinum-195 NMR spectroscopy. Phosphorous-31 NMR chemical shifts for these compounds lay in the range of 1.78–2.12 ppm for the fully deprotonated species. These compounds are remarkably stable with respect to hydrolysis in both the presence and absence of pyrophosphatase, with no loss of ligand observed in a week’s time at neutral pH. At pH 4, these compounds undergo slow acid-catalyzed hydrolysis resulting in the formation of pyrophosphato bridged dinuclear species. Platinum(II) pyrophosphato complexes were oxidized to trans-dihydroxo platinum(IV) analogues by reaction with hydrogen peroxide. This reaction follows second-order kinetics, with second-order rate constants lying between 2.3 and 4.9 M⁻¹s⁻¹. These rate constants were observed to be independent of pH in the range of 7-9. All compounds were observed to behave as diprotic acids, with pKₐ₁ values lying in the range of 1.2 to 2.9 and pKₐ₂ values in the range of 4.3 to 4.7. Proton NMR studies have shown that these complexes do not bind mononucleotides (dGMP, dAMP) or di-nucleotides (dGpG) within 48 hours at 25°C. In contrast, platinum(II) pyrophosphato complexes react readily with cysteine in a two-step process which first involves opening of the pyrophosphate chelate to form a monodentate intermediate with second-order rate constants lying between 1.4E-3 and 4.3E-3 M⁻¹s⁻¹, followed by deligation of the pyrophosphate ion. Reaction of platinum(IV) complexes with cysteine and glutathione occurs via reduction to platinum(II). These reactions are much slower than the corresponding reactions with platinum(II), with second-order rate constants on the order of 10⁻⁴ M⁻¹s⁻¹ for reaction with cysteine.Ph.D. (Doctor of Philosophy

Solitude chosen : images of introspection in the work of Andrew Wyeth

Includes bibliographical references (pages [92]-95).Traditional scholarly research on solitude in the work of American artists, including twentieth-century painter Andrew Wyeth, has frequently taken a pessimistic approach to this important theme. Wyeth's works often present solitude in a special context as a cherished moment of being in the world with an introspective focus. Beyond being a prominent theme in his work, solitude is omnipresent in Wyeth's daily existence, an essential part of his creative process. As a boy growing up in the home and studio of his father, N.C. Wyeth, Andrew Wyeth was prone to illness and was often left to himself. However, the artist consistently refers to this sort of upbringing in positive terms— as the ideal life for an artist. Beyond learning the craft of painting from his father in a studio setting, young Andrew was introduced to writers such as Henry David Thoreau and Robert Frost. Of these, N.C. was especially fond of Thoreau as a clear embodiment of a Romantic tradition— the artist who flourishes in isolation. In his adulthood, Andrew has lived as an artist with an intense desire for privacy— limiting himself to just two communities, Chadds Ford, Pennsylvania, and Cushing, Maine. The American transcendentalist goal of evoking a sense of the universal through an intense exploration of the particular is as present in Wyeth's imagery as in the writings of Ralph Waldo Emerson and Thoreau. Wyeth has been significantly influenced by these writers as well as past artists such as Winslow Homer, Thomas Eakins, Rembrandt and Albrecht Diirer. Wyeth's figural works often evoke a strong sense of detachment through many devices, including the avoidance of multiple figure compositions and the presentation of figures from a rear vantage point. These devices not only serve the goals which originated in the theories of Emerson and Thoreau, but also preserve and affirm the solitude of the detached figures. Andrew Wyeth presents solitude in a positive light, reveals a necessity for it, even romanticizes it. He opens up the value of solitude to his own audience not through images of alienation, loneliness or isolation, but through images of introspection.M.A. (Master of Arts

An aesthetic revolution : civic unrest, militarism and artistic revolt in the work of Umberto Boccioni

Includes bibliographical references (pages [64]-67)The Italian Futurists were a group of artists assembled in Paris and Milan with similar nationalistic concerns— radical change for Italy. They strove to bring Italy into the modern, industrial age, and out of its complacent reliance on past Italian artistic achievements. Despite the formal parallels between Futurism and other previous modern movements in painting and sculpture, the Italian artists sought to utilize modern formal principles as a means for social and political change, not as ends in themselves. Futurist artists were convinced they could revolutionize society through dynamic forms which reflected the fast-paced, technological advances of the twentieth century. Nevertheless, the visual arts were not the sole channel for change that the Futurists pursued. They were also interested in political and social revolution which, they fervently believed, would bring Italian culture into the modern age. While the political context of Futurism is often overlooked in a purely formal analysis, by focusing on Umberto Boccioni, one of the leaders of the movement, this thesis will trace the development of the movement's political ideology through a period of artistic inspiration into its military culmination. Strikingly evident in the writings of the Futurists was how seriously the movement hailed war above all as an inevitable and necessary means to purge Italy of its dependency on the past. It is ironic that war, which the Futurists so desired for Italy, essentially brought their movement to a standstill and led to the death of Boccioni. Therefore, the purpose of this thesis is to question whether these artists were misguided in their revolutionary ideas. Upon close inspection, it does appear that Boccioni's most important work was developed in an effort to use art to incite social revolution, culminating in war. This is a unique case in art history—where an artist's life work is directly dedicated to a cause—war—that, in turn, becomes the cause of his own annihilation. This paper will analyze the movement, its history, and its manifestations through Boccioni's writings and works in an effort to relate the productive formal changes to the destructive political results.M.A. (Master of Arts