Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis.

The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density.

C/EBPβ-LIP mediated activation of the malate-aspartate shuttle sensitizes cells to glycolysis inhibition.

Objective: Cancer cells use glycolysis for generation of metabolic intermediates and ATP needed for cell growth and proliferation. The transcription factor C/EBPβ-LIP stimulates glycolysis and mitochondrial respiration in cancer cells. We initially observed that high expression of C/EBPβ-LIP makes cells vulnerable to treatment with the glycolysis inhibitor 2-deoxyglucose.

Hepatic glutamine synthetase controls N-methylglutamine in homeostasis and cancer.

Glutamine synthetase (GS) activity is conserved from prokaryotes to humans, where the ATP-dependent production of glutamine from glutamate and ammonia is essential for neurotransmission and ammonia detoxification. Here, we show that mammalian GS uses glutamate and methylamine to produce a methylated glutamine analog, N-methylglutamine. Untargeted metabolomics revealed that liver-specific GS deletion and its pharmacological inhibition in mice suppress hepatic and circulating levels of N-methylglutamine.

C/EBPβ isoform-specific regulation of migration and invasion in triple-negative breast cancer cells.

The transcription factor C/EBPβ is a master regulator of mammary gland development and tissue remodelling during lactation. The CEBPB-mRNA is translated into three distinct protein isoforms named C/EBPβ-LAP1, -LAP2 and -LIP that are functionally different. The smaller isoform LIP lacks the N-terminal transactivation domains and is considered to act as an inhibitor of the transactivating LAP1/2 isoforms by competitive binding for the same DNA recognition sequences.

Ultrasensitive Photonic Microsystem Enabling Sub-micrometric Monitoring of Arterial Oscillations for Advanced Cardiovascular Studies.

Cardiovascular diseases are the first cause of death globally. Their early diagnosis requires ultrasensitive tools enabling the detection of minor structural and functional alterations in small arteries. Such analyses have been traditionally performed with video imaging-based myographs, which helped to investigate the pathophysiology of the microvessels.

C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the /LIN28B circuit in mice.

The transcription factors LAP1, LAP2 and LIP are derived from the -mRNA through the use of alternative start codons. High LIP expression has been associated with human cancer and increased cancer incidence in mice. However, how LIP contributes to cellular transformation is poorly understood.

Cell Culture Medium Formulation and Its Implications in Cancer Metabolism.

Historic cell culture media were designed to ensure continuous cancer cell proliferation in vitro. However, their composition does not recapitulate the nutritional environment of the tumor. Recent studies show that novel media formulations alleviate the nonphysiological constraints imposed by historic media, and lead to cell culture results that are more relevant to tumor metabolism.

Microfluidic-controlled optical router for lab on a chip.

In multiplexed analysis, lab on a chip (LoC) devices are advantageous due to the low sample and reagent volumes required. Although optical detection is preferred for providing high sensitivity in a contactless configuration, multiplexed optical LoCs are limited by the technological complexity for integrating multiple light sources and detectors in a single device. To address this issue, we present a microfluidic-controlled optical router that enables measurement in four individual optical channels using a single light source and detector, and without movable parts.

Label-Free Multi Parameter Optical Interrogation of Endothelial Activation in Single Cells using a Lab on a Disc Platform.

Cellular activation and inflammation leading to endothelial dysfunction is associated with cardiovascular disease (CVD). We investigated whether a single cell label-free multi parameter optical interrogation system can detect endothelial cell and endothelial progenitor cell (EPC) activation in vitro and ex vivo, respectively. Cultured human endothelial cells were exposed to increasing concentrations of tumour necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS) before endothelial activation was validated using fluorescence-activated cell sorting (FACS) analysis of inflammatory marker expression (PECAM-1, E-selectin and ICAM-1).

Improving the metabolic fidelity of cancer models with a physiological cell culture medium.

Currently available cell culture media may not reproduce the in vivo metabolic environment of tumors. To demonstrate this, we compared the effects of a new physiological medium, Plasmax, with commercial media. We prove that the disproportionate nutrient composition of commercial media imposes metabolic artifacts on cancer cells.

Reduced expression of C/EBPβ-LIP extends health and lifespan in mice.

Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the -mRNA.

A p300 and SIRT1 Regulated Acetylation Switch of C/EBPα Controls Mitochondrial Function.

Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes.

A screening strategy for the discovery of drugs that reduce C/EBPβ-LIP translation with potential calorie restriction mimetic properties.

An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA.

Plug and measure - a chip-to-world interface for photonic lab-on-a-chip applications.

The integration of detection mechanisms with microfluidics may be one of the most promising routes towards widespread application of Lab-on-a-Chip (LoC) devices. Photonic detection methods like in the so-called Photonic Lab-on-a-Chip (PhLoC) have advantages such as being non-invasive, easy to sterilize and highly sensitive even with short integration times and thus allow in situ monitoring and quantification of biological and chemical processes. The readout of such detection methods usually requires special training of potential users, as in most cases they are confronted with the need of establishing fiber-optics connections to and from the PhLoC and/or rely on the use of complex laboratory equipment.

Photonic Lab-on-a-Chip: Integration of Optical Spectroscopy in Microfluidic Systems.

The integration of micro-optical elements with microfluidics leads to the highly promising photonic lab-on-a-chip analytical systems (PhLoCs). In this work, we re-examine the main principles which are underneath the on-chip spectrophotometric detection, approaching the PhLoC concept to a nonexpert audience.

Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice.

The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of physiological adaptations in response to changes in nutrient supply. Major downstream targets of mTORC1 signalling are the mRNA translation regulators p70 ribosomal protein S6 kinase 1 (S6K1p70) and the 4E-binding proteins (4E-BPs). However, little is known about vertebrate mRNAs that are specifically controlled by mTORC1 signalling and are engaged in regulating mTORC1-associated physiology.

Microbial trench-based optofluidic system for reagentless determination of phenolic compounds.

Phenolic compounds are one of the main contaminants of soil and water due to their toxicity and persistence in the natural environment. Their presence is commonly determined with bulky and expensive instrumentation (e.g.

A multiple path photonic lab on a chip for parallel protein concentration measurements.

We propose a PDMS-based photonic system for the accurate measurement of protein concentration with minute amounts of the sample. As opposed to the state of the art approach, in the multiple path photonic lab on a chip (MPHIL), analyte concentration or molar absorptivity is obtained with a single injection step, by performing simultaneous parallel optical measurements varying the optical path length. Also, as opposed to the standard calibration protocol, the MPHIL approach does not require a series of measurements at different concentrations.

Tetrac can replace thyroid hormone during brain development in mouse mutants deficient in the thyroid hormone transporter mct8.

The monocarboxylate transporter 8 (MCT8) plays a critical role in mediating the uptake of thyroid hormones (THs) into the brain. In patients, inactivating mutations in the MCT8 gene are associated with a severe form of psychomotor retardation and abnormal serum TH levels. Here, we evaluate the therapeutic potential of the TH analog 3,5,3',5'-tetraiodothyroacetic acid (tetrac) as a replacement for T(4) in brain development.