The effects of iron deficiency and iron repletion on mitochondrial function: An in vivo study

Iron plays a central role in mitochondrial energy production, and this thesis provides insight into the mechanism by which mitochondria of energy demanding tissues are affected by iron deficiency and intravenous iron repletion in the mouse. Administration of an iron-deficient diet in mice led to iron deficiency, and in some cases anaemia. This deficiency was tested by measuring haemoglobin, serum ferritin, cardiac iron, and spleen iron concentrations and comparing them with a group of mice fed a control diet. Using biochemical assays and high resolution respirometry, it was shown that iron deficiency induced a decrease in activity of some, but not all, mitochondrial complexes within cardiac muscle, which is restored following intravenous iron repletion. Mitochondrial function in skeletal muscle tissue, namely the soleus and not the quadriceps, decreased in response to iron deficiency, but was partially restored following intravenous iron repletion. Iron deficiency also led to a decrease in in-gel activity of supramolecular complex II of the soleus, which remained uncorrected following iron repletion. Immunohistochemistry and western blot analysis of skeletal muscle tissue demonstrated that these functional changes occur in the absence of structural differences, i.e., the number of mitochondria, or the connectedness of mitochondria. Changes in cortical oxygenation and metabolism were assessed non-invasively, using broadband near-infrared spectroscopy. Iron deficient mice show a metabolic vulnerability, and an attenuated response in changes of deoxygenated haemoglobin during exposure to hypoxia, while iron repleted mice demonstrate an enhanced metabolic recovery following hypoxia. Additionally, iron deficiency induced a drop in synaptic marker expression in the brain, which was partially restored after repletion in certain areas of the brain. This research validated a murine model of adult iron deficiency and intravenous iron repletion and provided new insights into the effects iron deficiency and intravenous iron repletion on mitochondrial physiology

A Textbook Example of International Price Discrimination

We investigate differences in book prices between the United States and other countries. We find that general audience books are similarly priced internationally, but textbooks are substantially more expensive in the United States (often more than double the price). This disparity is much more pronounced for commercial publishers than for university presses. We argue that supply-side factors like cost and market structure can not explain this phenomenon. We discuss several demand-side explanations; our preferred theory is that higher US textbook prices reflect the unique status of the textbook as a centerpiece of US college instruction.international price discrimination, book industry, textbooks

R&D investments fostering horizontal mergers

We study a homogenous good triopoly in which firms first choose their cost-reducing R&D investments and consider alternative merger proposals, and then compete à la Cournot in the ensuing industry. We identify conditions under which both horizontal mergers and non integration are sustained by Coalition-Proof Nash equilibria (CPNE). These conditions involve the effectiveness of the R&D technology, as well as the distribution of the bargaining power between the acquirer and the acquiree, which determine the allocation of the incremental profits generated by the merger. We show that whether firms follow duplicative or complementary research paths, sustaining a merger generally requires a sufficiently effective R&D technology that creates endogenous cost asymmetries and renders the merger profitable, and a moderate distribution of bargaining power that allows to spread the benefits of the merger. We examine the welfare effects of mergers and obtain clear policy guidelines.We would like to thank Lindsay McTeague for editorial assistance, and John Geanakoplos, Patrick Rey and participants of research seminars at Düsseldorf Institute for Competition Economics, the Higher School of Economics (Moscow), and the University of Cyprus for helpful comments and suggestions. Part of this work was supported by COST Action IS1104 “The EU in the new economic complex geography: models, tools and policy evaluation”. Moreno acknowledges financial support from the Ministerio Economía y Competitividad (Spain), grants ECO2014-55953-P and MDM2014-0431, and from the Comunidad de Madrid, grant S2015/HUM-3444

Semiconductors: NEC: Sustaining long-term advantage through information technology

The case begins by placing the Japanese semiconductor industry in global context and examining the governmental policies and subsequent growth of the domestic and international semiconductor markets. As Japan's leading semiconductor producer, NEC's evolution and current business strategies are an integral part of this development. At the same time, the study of NEC's organizational structure and product choice allows an understanding of the company's use of and demand for software. The case study concludes by examining the use of information technology as a tool to create competitive advantage

The misogyny of iron deficiency

Anaemia is common, particularly in women and the commonest underlying cause, iron deficiency, is often overlooked. Anaemia is associated with increased morbidity and mortality in patients undergoing anaesthesia; however, women are defined as being anaemic at a lower haemoglobin level than men. In this narrative review, we present the history of iron deficiency anaemia and how women’s health has often been overlooked. Iron deficiency was first described as ‘chlorosis’ and a cause of ‘hysteria’ in women and initial treatment was by iron filings in cold wine. We present data of population screening demonstrating how common iron deficiency is, affecting 12–18% of apparently ‘fit and healthy’ women, with the most common cause being heavy menstrual bleeding; both conditions being often unrecognised. We describe a range of symptoms reported by women, that vary from fatigue to brain fog, hair loss and eating ice. We also describe experiments exploring the physical impact of iron deficiency, showing that reduced exercise performance is related to iron deficiency independent of haemoglobin concentration, as well as the impact of iron supplementation in women improving oxygen consumption and fitness. Overall, we demonstrate the need to single out women and investigate iron deficiency rather than accept the dogma of normality and differential treatment; this is to say, the need to change the current standard of care for women undergoing anaesthesia

Multisensory interactions in Virtual Reality: optic flow reduces vestibular sensitivity, but only for congruent planes of motion

During exposure to Virtual Reality (VR) a sensory conflict may be present, whereby the visual system signals that the user is moving in a certain direction with a certain acceleration, while the vestibular system signals that the user is stationary. In order to reduce this conflict, the brain may down-weight vestibular signals, which may in turn affect vestibular contributions to self-motion perception. Here we investigated whether vestibular perceptual sensitivity is affected by VR exposure. Participants’ ability to detect artificial vestibular inputs was measured during optic flow or random motion stimuli on a VR head-mounted display. Sensitivity to vestibular signals was significantly reduced when optic flow stimuli were presented, but importantly this was only the case when both visual and vestibular cues conveyed information on the same plane of self-motion. Our results suggest that the brain dynamically adjusts the weight given to incoming sensory cues for self-motion in VR; however this is dependent on the congruency of visual and vestibular cues

Somatosensory modulation of perceptual vestibular detection

Vestibular-multisensory interactions are essential for self-motion, navigation and postural stability. Despite evidence suggesting shared brain areas between vestibular and somatosensory inputs, no study has yet investigated whether somatosensory information influences vestibular perception. Here, we used signal detection methods to identify whether somatosensory stimulation might interact with vestibular events in a vestibular detection task. Participants were instructed to detect near-threshold vestibular roll-rotation sensations delivered by galvanic vestibular stimulation in one-half of experimental trials. A vibrotactile signal occurred to the index fingers of both hands in half of the trials, independent of vestibular signals. We found that vibrotactile somatosensory stimulation decreased perceptual vestibular sensitivity. The results are compatible with a gain regulation mechanism between vestibular and somatosensory modalities