A Network Perspective on Metabolic Inconsistency
Sonnenschein N, Golib Dzib JF, Lesne A, Eilebrecht S, Boulkroun S, Zennaro MC, Benecke A, Hütt MT.
BMC Syst Biol. 2012 May 14;6(1):41. [Epub ahead of print]
PMID: 22583819 [PubMed - as supplied by publisher]
Background
Integrating gene expression profiles and metabolic pathways under different experimental conditions is... more
Background
Integrating gene expression profiles and metabolic pathways under different experimental conditions is essential for understanding the coherence of these two layers of cellular organization. The network character of metabolic systems can be instrumental in developing concepts of agreement between expression data and pathways. A network-driven interpretation of gene expression data has the potential of suggesting novel classifiers for pathological cellular states and of contributing to a general theoretical understanding of gene regulation.
Results
Here, we analyze the coherence of gene expression patterns and a reconstruction of human metabolism, using consistency scores obtained from network and constraint-based analysis methods. We find a surprisingly strong correlation between the two measures, demonstrating that a substantial part of inconsistencies between metabolic processes and gene expression can be understood from a network perspective alone. Prompted by this finding, we investigate the topological context of the individual biochemical reactions responsible for the observed inconsistencies. On this basis, we are able to separate the differential contributions that bear physiological information about the system, from the unspecific contributions that unravel gaps in the metabolic reconstruction. We demonstrate the biological potential of our network-driven approach by analyzing transcriptome profiles of aldosterone producing adenomas that have been obtained from a cohort of Primary Aldosteronism patients. We unravel systematics in the data that could not have been resolved by conventional microarray data analysis. In particular, we discover two distinct metabolic states in the adenoma expression patterns.
Conclusions
The methodology presented here can help understand metabolic inconsistencies from a network perspective. It thus serves as a mediator between the topology of metabolic systems and their dynamical function. Finally, we demonstrate how physiologically relevant insights into the structure and dynamics of metabolic networks can be obtained using this novel approach.
Shilajit Moomiyo also called Mumiyo is an energy metabolism booster
by Andy Kahn
Shilajit moomiyo is an adaptogenic herb which can be used to enhance physical and mental performance. Shilajit is believed to amplify the benefits of other herbs by enhancing their bio-availability. Shilajit is also believed to increase protein synthesis, growth rate and/or energy intake. Suitably, the nutritional composition can include a Shilajit material or extract which has been standardized to include or contain 10% humic acid and/or 10% fulvic acid. In accordance with certain other embodiments, the nutritional composition can alternatively and/or additionally contain fulvic acid, humic acid, and/or another botanical, natural, or herbal source of fulvic acid and/or humic acid.
Shilajit moomiyo is an adaptogenic herb which can be used to enhance physical and mental performance. Shilajit is... more
Shilajit moomiyo is an adaptogenic herb which can be used to enhance physical and mental performance. Shilajit is believed to amplify the benefits of other herbs by enhancing their bio-availability. Shilajit is also believed to increase protein synthesis, growth rate and/or energy intake. Suitably, the nutritional composition can include a Shilajit material or extract which has been standardized to include or contain 10% humic acid and/or 10% fulvic acid. In accordance with certain other embodiments, the nutritional composition can alternatively and/or additionally contain fulvic acid, humic acid, and/or another botanical, natural, or herbal source of fulvic acid and/or humic acid.
Shilajit plays an important part in boosting the energy metabolism process in the body. Anabolism is a key factor in the process of muscle growth for athletes and body builders. Anabolism is comprised of multiple metabolic pathways, constructing larger molecules from their building blocks. Energy is a necessary part of these metabolic pathways. In contrast, catabolism is the deconstruction of large molecules into smaller ones. Anabolism is fueled by both the small molecules of catabolism as well as an energy source, such as, but not limited to, adenosine triphosphate (ATP). The anabolic process and related anabolic hormones stimulate protein synthesis and muscle growth. Anabolic reactions are synthesis reactions and are endergonic, meaning that they consume more energy than they produce. Anabolism is the process of chemical reactions that combine simple molecules and monomers to form the body's complex structural and functional components. Glucose may take part in or be formed via several anabolic reactions such as, for example, synthesis of glycogen or the synthesis of new glucose molecules from byproducts of protein and lipid breakdown, i.e., gluconeogenesis. One way of promoting anabolism is through the use of a dietary supplement or drug. However, many anabolic stimulation compositions are illegal or have been banned from use by athletes in a number of professional, collegiate, and amateur sports. Additionally, anabolic stimulating products also generally tend to have undesired side effects that can be harmful to the health of an individual. Thus, there is a need and a demand for a dietary ingredient or composition which can promote anabolism without undesirable side effects and/or which is suitable for use by athletes. For the most part, anabolism is increased where there is an energy source and a way to synthesize proteins and therefore build new muscle. One energy source is ATP. Alternative energy sources include compounds or methods to increase metabolism. The ability and rate at which the body can spare and replenish energy is critical for anabolism.
Shilajit contains 85 types of minerals in the natural ionic form which are very vital for maintaining the equilibrium of energy metabolism in our body. The minerals in Shilajit are not similar to the mineral supplements available in the market. The minerals in Shilajit are in ionic form and have previously been absorbed by rich plant life and returned back to earth. So they are easily absorbed by the body cells.
FULVIC ACID the major ingredient of the Shilajit plays a vital role in penetrating the cell walls and transporting the minerals deep into the cells. This is the most important property of the Shilajit that helps in arresting and reversing the aging process. With shilajit ensuring sufficient supply of minerals and vitamins deep into the body cells the energy metabolism process in the body is well maintained.
Metabolism Reconsidered. Its Role in the Architectural Context of the World
published in: JAABE - Journal of Asian Architecture and Building Engineering (英文論文集), Architectural Institute of Japan - Tokyo, Vol. 3, No. 2, November 2004, pp. 357-363
This paper analyzes and considers the main features of the Japanese avant-garde movement ″Metabolism″ that appeared on... more This paper analyzes and considers the main features of the Japanese avant-garde movement ″Metabolism″ that appeared on the scene of the architectural world in the early 60s. The originality of the concepts developed by its members and the innovative design of their projects captured the attention of many critics, in Japan as well as abroad, who often either misunderstood or neglected most of the original theories of the group. Therefore, it seems that furthermore analysis could be necessary to clarify some points of metabolist group′s activity, and to reach a better understanding of the historical context in which Metabolism has originated and developed, as well as of its aims.
The Issue of Tokyo Bay’s Reclaimed Lands as the Origin of Urban Utopias in Modern Japanese Architecture
published in: Journal of Architecture and Planning (Transactions of AIJ - Architectural Institute of Japan), Tokyo, No. 613, March 2007, pp. 259-266
This paper aims to investigate from a broader point of view as in 1958 the theme of development of Tokyo into the sea... more This paper aims to investigate from a broader point of view as in 1958 the theme of development of Tokyo into the sea by reclaiming lands of her coasts became the occasion for the productions on several projects which witnessed the innovative potentials and the talent of a new generation of architects, such as the members of Metabolist Group and Kenzo Tange, who had a great impact on the further development of the modern Japanese architecture. Those proposals were a mirror of their original vision of the modern city, which was mainly inspired by many cultural and socio-economical factors present at the time in Japan, such as the uncontrolled sprawl of the cities, the radical transformation of Japanese society and the massive alteration of historical urban landscapes due to post-war urbanism and economic growth, as well as the search for a new urban form and design methodology more concerned about the preservation of the natural landscape, and directly linked with the new possibilities offered by ocean engineering and new building technology.
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Dynamic Mitochondrial Networks in Cancer
Published on the Scientific American Blog
Research projects evolve in a fortuitous manner, often guided by a convergence of novel observations, intuition,... more
Research projects evolve in a fortuitous manner, often guided by a convergence of novel observations, intuition, helpful colleagues and unique personal circumstances. It is precisely this constellation that prompted two cardiologists to study the mitochondrial networks in lung cancer cells.
In 2008, my colleague and friend Stephen Archer, a Professor of Medicine at the University of Chicago, asked me whether I would be interested in studying the role of mitochondrial networks in lung cancer cells. My first response was the question “Do mitochondria really form networks?”, because at that time the expression “mitochondria” evoked images of scattered oval-like organelles, a textbook image of electron microscopy.......
The changes they are a-timed: metabolism, endogenous clocks, and the timing of puberty
Childhood obesity has increased dramatically over the last several decades, particularly in industrialized countries,... more Childhood obesity has increased dramatically over the last several decades, particularly in industrialized countries, often accompanied by acceleration of pubertal progression and associated reproductive abnormalities (Biro et al., 2006; Rosenfield et al., 2009). The timing of pubertal initiation and progression in mammals is likely influenced by nutritional and metabolic state, leading to the hypothesis that deviations from normal metabolic rate, such as those seen in obesity, may contribute to observed alterations in the rate of pubertal progression. While several recent reviews have addressed the effects of metabolic disorders on reproductive function in general, this review will explore previous and current models of pubertal timing, outlining a potential role of endogenous timing mechanisms such as cellular circadian clocks in the initiation of puberty, and how these clocks might be altered by metabolic factors. Additionally, we will examine recently elucidated neuroendocrine regulators of pubertal progression such as kisspeptin, explore models detailing how the mammalian reproductive axis is silenced during the juvenile period and reactivated at appropriate developmental times, and emphasize how metabolic dysfunction such as childhood obesity may alter timing cues that advance or delay pubertal progression, resulting in diminished reproductive capacity.
XXVIII
by A Nonomura
Co-authored with Andrew A. Benson and Barry A. Cullen
Published in Advances in Photosynthesis, 2012, Intech, ISBN 978-953-307-928-8
Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer
Published in the FASEB Journal
Mitochondria exist in dynamic networks that undergo fusion and fission. Mitochondrial fusion and fission are mediated... more Mitochondria exist in dynamic networks that undergo fusion and fission. Mitochondrial fusion and fission are mediated by several GTPases in the outer mitochondrial membrane, notably mitofusin-2 (Mfn-2), which promotes fusion, and dynamin-related protein (Drp-1), which promotes fission. We report that human lung cancer cell lines exhibit an imbalance of Drp-1/Mfn-2 expression, which promotes a state of mitochondrial fission. Lung tumor tissue samples from patients demonstrated a similar increase in Drp-1 and decrease in Mfn-2 when compared to adjacent healthy lung. Complementary approaches to restore mitochondrial network formation in lung cancer cells by overexpression of Mfn-2, Drp-1 inhibition, or Drp-1 knockdown resulted in a marked reduction of cancer cell proliferation and an increase in spontaneous apoptosis. The number of cancer cells in S phase decreased from 32.4 ± 0.6 to 6.4 ± 0.3% with Drp-1 inhibition (P<0.001). In a xenotransplantation model, Mfn-2 gene therapy or Drp-1 inhibition could regress tumor growth. The tumor volume decreased from 205.6 ± 59 to 70.6 ± 15 mm(3) (P<0.05) with Mfn-2 overexpression and from 186.0 ± 19 to 87.0 ± 6 mm(3) (P<0.01) with therapeutic Drp-1 inhibition. Impaired fusion and enhanced fission contribute fundamentally to the proliferation/apoptosis imbalance in cancer and constitute promising novel therapeutic targets.
The Path of Carbon in Photosynthesis. XXVIII
by A Nonomura
Andrew A. Benson
Part 3, The Path of Carbon in Photosynthesis.
Chapter 13, Advances in Photosynthesis-Fundamental Aspects, InTech
Benson Calvin Cycle Benson Calvin Cycle
Novel proteins of the phosphotransferase system encoded within the …
Powell, BS, Court DL, Inada T, Nakamura Y, Michotey V, Cui X, Reizer A, Saier MH, Jr, Reizer J. J Biol Chem. 1995 Mar 3;270(9):4822-39.
Two rpoN-linked delta Tn10-kan insertions suppress the conditionally lethal erats allele. One truncates rpoN while the... more Two rpoN-linked delta Tn10-kan insertions suppress the conditionally lethal erats allele. One truncates rpoN while the second disrupts another gene (ptsN) in the rpoN operon and does not affect classical nitrogen regulation. Neither alter expression of era indicating that suppression is post-translational. Plasmid clones of ptsN prevent suppression by either disruption mutation indicating that this gene is important for lethality caused by erats. rpoN and six neighboring genes were sequenced and compared with sequences in the database. Two of these genes encode proteins homologous to Enzyme IIAFru and HPr of the phosphoenolpyruvate:sugar phosphotransferase system. We designate these proteins IIANtr (ptsN) and NPr (npr). Purified IIANtr and NPr exchange phosphate appropriately with Enzyme I, HPr, and Enzyme IIA proteins of the phosphoenolpyruvate: sugar phosphotransferase system. Several sugars and tricarboxylic acid cycle intermediates inhibited growth of the ptsN disruption mutant on medium containing an amino acid or nucleoside base as a combined source of nitrogen, carbon, and energy. This growth inhibition was relieved by supplying the ptsN gene or ammonium salts but was not aleviated by altering levels of exogenously supplied cAMP. These results support our previous proposal of a novel mechanism linking carbon and nitrogen assimilation and relates IIANtr to the unknown process regulated by the essential GTPase Era.
Barley mutants with low rates of endosperm starch synthesis have low grain dormancy and high susceptibility to pre-harvest sprouting
New Phytologist | In Press
• Studies of embryo dormancy in relation to pre-harvest sprouting (PHS) in cereals have focussed on ABA and other... more
• Studies of embryo dormancy in relation to pre-harvest sprouting (PHS) in cereals have focussed on ABA and other hormones. The relationship between these phenomena and the rate of grain filling has not been investigated.
• A collection of barley mutants impaired in starch synthesis was assessed for pre-harvest sprouting in the field. In subsequent glasshouse experiments, developing grains were assayed for germination index, sugars, abscisic acid (ABA), and the effects of temperature and exogenous ABA on germination.
• Mutant lines displayed greater pre-harvest sprouting in the field than parental lines. In the glasshouse, non-deep physiological dormancy was reduced in developing grains of five lines with mutations affecting proteins involved in endosperm starch synthesis. Inhibition of germination by exogenous ABA and elevated temperature was decreased in developing mutant grains. Sugar levels were high but embryo and endosperm ABA contents were unaltered.
• We reveal a direct connection between grain filling and the extent of grain dormancy. Impaired endosperm starch synthesis directly influences the acquisition of embryo dormancy, perhaps because endosperm sugar levels modulate the ABA responsiveness of the embryo. Thus environmental or genetic factors that reduce grain filling are likely to reduce dormancy and enhance susceptibility to PHS.
The Metabolic Reprogramming Evoked by Nitrosative Stress Triggers the Anaerobic Utilization of Citrate in Pseudomonas fluorescens
Nitrosative stress is an ongoing challenge that most organisms have to contend with. When nitric oxide (NO) that may... more Nitrosative stress is an ongoing challenge that most organisms have to contend with. When nitric oxide (NO) that may be generated either exogenously or endogenously encounters reactive oxygen species (ROS), it produces a set of toxic moieties referred to as reactive nitrogen species (RNS). As these RNS can severely damage essential biomolecules, numerous organisms have evolved elaborate detoxification strategies to nullify RNS. However, the contribution of cellular metabolism in fending off nitrosative stress is poorly understood. Using a variety of functional proteomic and metabolomic analyses, we have identified how the soil microbe Pseudomonas fluorescens reprogrammed its metabolic networks to survive in an environment enriched by sodium nitroprusside (SNP), a generator of nitrosative stress. To combat the RNS-induced ineffective aconitase (ACN) and tricarboxylic acid (TCA) cycle, the microbe invoked the participation of citrate lyase (CL), phosphoenolpyruvate carboxylase (PEPC) and pyruvate phosphate dikinase (PPDK) to convert citrate, the sole source of carbon into pyruvate and ATP. These enzymes were not evident in the control conditions. This metabolic shift was coupled to the concomitant increase in the activities of such classical RNS detoxifiers as nitrate reductase (NR), nitrite reductase (NIR) and S-nitrosoglutathione reductase (GSNOR). Hence, metabolism may hold the clues to the survival of organisms subjected to nitrosative stress and may provide therapeutic cues against RNS-resistant microbes.
Another gentle manifesto towards complexity, contradiction, multiplicity and pluralist democracy for the inhabitants of modern cities
This is a preliminary draft of a study for a "dialexis" paper, later evolved to a different and larger analysis sharing some similar views, under the title: "Three analytic quasi methods, for a schizoanalytical urban experiment".
The present paper was written in May 2011, at Tecnica University of Lisbon, under professor Carlos Alho. The later paper was completed in Greek, in October 2011, under professor Dimitris Papalexopoulos of Technical University of Athens.
About residential architecture of modern metropolises, the choice or absence of choice that they offer for their... more About residential architecture of modern metropolises, the choice or absence of choice that they offer for their inhabitants, and the totalitarian aspect of architecture of the age of modernity. It focuses on the city of Athens, Greece, and at the end it proposes some kind of flexible and metabolizing urbanism.

