Recent advances in expanding the coverage of the lipidome

The lipidome comprises a large array of molecules with diverse physicochemical properties. Lipids are structural components of cells, act as a source of energy, and function as signaling mediators. Alterations in lipid metabolism are involved in the onset and progression of a variety of diseases, including metabolic syndrome and cancer. Because of this, interest in lipidomics, the comprehensive characterization of the lipidome by mass spectrometry, has intensified in recent years. However, obtaining a truly complete overview of all lipids in a sample has remained very challenging due to their enormous structural diversity. Here, we provide an overview of the collection of analytical approaches used to study various lipid classes, emphasizing innovations in sample preparation and liquid chromatography–mass spectrometry (LC–MS). Additionally, we provide practical suggestions for increasing the coverage of the lipidome

Editorial overview: recent innovations in the metabolomics revolution

No abstract available

Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating

Cancer is fundamentally a disease of uncontrolled cell proliferation. Tumour metabolism has emerged as an exciting new discipline studying how cancer cells obtain the necessary energy and cellular ‘building blocks’ to sustain growth. Glucose and glutamine have long been regarded as the key nutrients fuelling tumour growth. However, the inhospitable tumour microenvironment of certain cancers, like pancreatic cancer, causes the supply of these nutrients to be chronically insufficient for the demands of proliferating cancer cells. Recent work has shown that cancer cells are able to overcome this nutrient insufficiency by scavenging alternative substrates, particularly proteins and lipids. Here, we review recent work identifying the endocytic process of macropinocytosis and subsequent lysosomal processing as an important substrate-acquisition route. In addition, we discuss the impact of hypoxia on fatty acid metabolism and the relevance of exogenous lipids for supporting tumour growth as well as the routes by which tumour cells can access these lipids. Together, these cancer-specific scavenging pathways provide a promising opportunity for therapeutic intervention

Mean-Field and Non-Mean-Field Behaviors in Scale-free Networks with Random Boolean Dynamics

We study two types of simplified Boolean dynamics over scale-free networks, both with synchronous update. Assigning only Boolean functions AND and XOR to the nodes with probability $1-p$ and $p$, respectively, we are able to analyze the density of 1's and the Hamming distance on the network by numerical simulations and by a mean-field approximation (annealed approximation). We show that the behavior is quite different if the node always enters in the dynamic as its own input (self-regulation) or not. The same conclusion holds for the Kauffman KN model. Moreover, the simulation results and the mean-field ones (i) agree well when there is no self-regulation, and (ii) disagree for small $p$ when self-regulation is present in the model.Comment: 12 pages, 7 figure

Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate

Background Cell growth requires fatty acids for membrane synthesis. Fatty acids are assembled from 2-carbon units in the form of acetyl-CoA (AcCoA). In nutrient and oxygen replete conditions, acetyl-CoA is predominantly derived from glucose. In hypoxia, however, flux from glucose to acetyl-CoA decreases, and the fractional contribution of glutamine to acetyl-CoA increases. The significance of other acetyl-CoA sources, however, has not been rigorously evaluated. Here we investigate quantitatively, using 13C-tracers and mass spectrometry, the sources of acetyl-CoA in hypoxia.<p></p> Results In normoxic conditions, cultured cells produced more than 90% of acetyl-CoA from glucose and glutamine-derived carbon. In hypoxic cells, this contribution dropped, ranging across cell lines from 50% to 80%. Thus, under hypoxia, one or more additional substrates significantly contribute to acetyl-CoA production. 13C-tracer experiments revealed that neither amino acids nor fatty acids are the primary source of this acetyl-CoA. Instead, the main additional source is acetate. A large contribution from acetate occurs despite it being present in the medium at a low concentration (50–500 μM).<p></p> Conclusions Acetate is an important source of acetyl-CoA in hypoxia. Inhibition of acetate metabolism may impair tumor growth.<p></p&gt

The 2014 Beatson International Cancer Conference: Powering the Cancer Machine

Here, we present a report of the 2014 annual Beatson International Cancer Conference, Glasgow, July 6–9, 2014. The theme was “Powering the Cancer Machine”, focusing on oncogenic signals that regulate metabolic rewiring and the adaptability of the metabolic network in response to stress

Cancer metabolism at a glance

A defining hallmark of cancer is uncontrolled cell proliferation. This is initiated once cells have accumulated alterations in signaling pathways that control metabolism and proliferation, wherein the metabolic alterations provide the energetic and anabolic demands of enhanced cell proliferation. How these metabolic requirements are satisfied depends, in part, on the tumor microenvironment, which determines the availability of nutrients and oxygen. In this Cell Science at a Glance paper and the accompanying poster, we summarize our current understanding of cancer metabolism, emphasizing pathways of nutrient utilization and metabolism that either appear or have been proven essential for cancer cells. We also review how this knowledge has contributed to the development of anticancer therapies that target cancer metabolism

In praise of death : history and poetry in medieval Marwar (South Asia)

This study of heroic and epic “war poetry” transmitted by the poets of pastoral-nomadic communities in medieval Marwar (Rajasthan) evokes the lived past of the Rajput, Bhil and Charan of the Marwari desert with a detailed analysis of poetic sources concerning Pabuji, a fourteenth-century warrior and present-day Hindu god. The author, who undertook three years of archival and anthropological research in western Rajasthan, offers an interpretation of Pabuji’s world that allows us to look afresh at the narrative process of deification and the related construction of socio-political and religious identities in South Asia. Employing historical, literary and socio-linguistic approaches to shed light on the form and content of medieval poetry dedicated to Pabuji, this multi-disciplinary study sets forth the relation between Rajasthan’s warlike history, the politico-military purpose of its poetry and the religiously inspired ideal of self sacrifice in battle. Also part of this study is an introduction to the history and prosody of medieval Dimgal, a specialized Rajasthani poetic idiom, as well as a full academic transliteration of the selected medieval and contemporary poems.LEI Universiteit LeidenResearch School CNWSAsian Studie