Is the Madden–Julian Oscillation reliably detectable in Schumann Resonances?

The Madden-Julian Oscillation (MJO) is a quasi-periodic (30-90 days) eastward-moving atmospheric mode which primarily modifies rainfall patterns in the equatorial regions from Africa to the Pacific Ocean. It has been proposed that its signature is detectable within the intensity variations of the Schumann Resonances (SR) due to changes in the location and magnitude of the major lightning centres. Using six years of induction coil data recorded at the Eskdalemuir Observatory in the UK, we investigate whether the MJO is detectable in the first three Schumann Resonances. We extract the frequency and intensity values from each resonance every 10 min, averaged to a daily value and compare them to the Realtime Multivariate MJO (RMM) index. We use Empirical Mode Decomposition (EMD) to determine if certain modes correlate between the SR and RMM curves. We find that the EMD 30 to 70 day modes of the SR and RMM index occasionally beat in-phase during the La Niña periods of the El Niño Southern Oscillation (ENSO) but not El Niño periods. However, the relationship is not wholly consistent, implying that robust and reliable detection of the MJO in SR data remains challenging

Signals from the Niche: Insights into the Role of IGF-1 and IL-6 in Modulating Skeletal Muscle Fibrosis

Abstract Muscle regeneration, characterized by the activation and proliferation of satellite cells and other precursors, is accompanied by an inflammatory response and the remodeling of the extracellular matrix (ECM), necessary to remove cellular debris and to mechanically support newly generated myofibers and activated satellite cells. Muscle repair can be considered concluded when the tissue architecture, vascularization, and innervation have been restored. Alterations in these connected mechanisms can impair muscle regeneration, leading to the replacement of functional muscle tissue with a fibrotic scar. In the present review, we will discuss the cellular mediators of fibrosis and how the altered expression and secretion of soluble mediators, such as IL-6 and IGF-1, can modulate regulatory networks involved in the altered regeneration and fibrosis during aging and diseases

Metabolic changes associated with muscle expression of SOD1G93A

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder, classified into sporadic or familial forms and characterized by motor neurons death, muscle atrophy, weakness, and paralysis. Among the familial cases of ALS, approximately 20% are caused by dominant mutations in the gene coding for superoxide dismutase (SOD1) protein. Of note, mutant SOD1 toxicity is not necessarily limited to the central nervous system. ALS is indeed a multi-systemic and multifactorial disease that affects whole body physiology and induces severe metabolic changes in several tissues, including skeletal muscle. Nevertheless, whether alterations in the plasticity, heterogeneity, and metabolism of muscle fibers are the result of motor neuron degeneration or alternatively occur independently of it remain to be elucidated. To address this issue, we made use of a mouse model (MLC/SOD1G93A) that overexpresses the SOD1 mutant gene selectively in skeletal muscle. We found an alteration in the metabolic properties of skeletal muscle characterized by alteration in fiber type composition and metabolism. Indeed, we observed an alteration of muscle glucose metabolism associated with the induction of Phosphofructokinases and Pyruvate dehydrogenase kinase 4 expression. The upregulation of Pyruvate dehydrogenase kinase 4 led to the inhibition of Pyruvate conversion into Acetyl-CoA. Moreover, we demonstrated that the MLC/SOD1G93Atransgene was associated with an increase of lipid catabolism and with the inhibition of fat deposition inside muscle fibers. All together these data demonstrate that muscle expression of the SOD1G93Agene induces metabolic changes, along with a preferential use of lipid energy fuel by muscle fibers. We provided evidences that muscle metabolic alterations occurred before disease symptoms and independently of motor neuron degeneration, indicating that skeletal muscle is likely an important therapeutic target in ALS

Effects of IGF\u20101 isoforms on muscle growth and sarcopenia

The decline in skeletal muscle mass and strength occurring in aging, referred as sar\u2010copenia, is the result of many factors including an imbalance between protein synthe\u2010sis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin\u2010like growth factor\u20101 (IGF\u20101) has been implicated in many anabolic pathways in skeletal muscle. IGF\u20101 exists in different isoforms that might exert differ\u2010ent role in skeletal muscle. Here we study the effects of two full propeptides IGF\u20101Ea and IGF\u20101Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF\u20101Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF\u20101Ea or IGF\u20101Eb transgenes was protective against age\u2010related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase P GC1\u2010\u3b1 expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF\u20101Ea and MLC/IGF\u20101Eb mice during aging. These data suggest that IGF\u20101 is a promising thera\u2010peutic agent in staving off advancing muscle weakness

Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol

Correction: Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

[This corrects the article DOI: 10.1371/journal.pone.0137999.]

Secretory products from PC-3 and MCF-7 tumor cell lines upregulate osteopontin in MC3T3-E1 cells

Tumor cells frequently have pronounced effects on the skeleton including bone destruction, bone pain, hypercalcemia, and depletion of bone marrow cells. Despite the serious sequelae associated with skeletal metastasis, the mechanisms by which tumor cells alter bone homeostasis remain largely unknown. In this study, we tested the hypothesis that the disruption of bone homeostasis by tumor cells is due in part to the ability of tumor cells to upregulate osteopontin (OPN) mRNA in osteoblasts. Conditioned media were collected from tumor cells that elicit either osteolytic (MCF-7, PC-3) or osteoblastic responses (LNCaP) in animal models and their effects on OPN gene expression were compared using an osteoblast precursor cell line, MC3T3-E1 cells. Secretory products from osteolytic but not osteoblastic tumor cell lines were demonstrated to upregulate OPN in osteoblasts while inhibiting osteoblast proliferation and differentiation. Signal transduction studies revealed that regulation of OPN was dependent on both protein kinase C (PKC) and the mitogen-activated protein (MAP) kinase cascade. These results suggest that the upregulation of OPN may play a key role in the development of osteolytic lesions. Furthermore, these results suggest that drugs that prevent activation of the MAP kinase pathway may be efficacious in the treatment of osteolytic metastases. J. Cell. Biochem. 78:607–616, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34901/1/10_ftp.pd

Diversamente umani: retoriche e realt\ue0 dell'umanitarismo

Il saggio tenta di spiegare la contraddizione tra retoriche e realt\ue0 dell\u2019umanitarismo. Da dove deriva il cortocircuito tra la compassione e la paura che coinvolge il modo di pensare dei singoli individui come il legiferare delle istituzioni? Per comprendere questo alternarsi di emozioni caritatevoli e pulsione securitaria il saggio muove dal presupposto che, in quanto problema sociale, l\u2019immigrazione \ue8 un oggetto culturale: ovvero un costrutto artificiale, prodotto di contingenze storiche, rispondente ad una interpretazione condivisa che si adegua ad un contesto di idee e di istituzioni, e che suggerisce atteggiamenti e azioni. Privilegiando il piano analitico su quello normativo, il saggio esplora il ruolo del discorso umanitario nella costruzione emotiva, cognitiva e politica dei processi di interazione tra migranti e societ\ue0 ospiti. Un problema che non \ue8 psicologico n\ue9 esclusivamente etico, ma strettamente sociologico, in quanto ancora prima che il contenuto delle politiche adottate nei confronti dell'altro, ci\uf2 che rileva \ue8 la dimensione cognitiva, i processi di categorizzazione e di etichettamento, il frame attraverso cui viene attribuita a questi una specifica identit\ue0 e dal quale conseguono stili e contenuti delle politiche. Se, infatti, l'altro \ue8 considerato una vittima, un deviante, un povero o un lavoratore-ospite, il contenuto, le finalit\ue0, le modalit\ue0 di organizzazione e di realizzazione delle politiche variano di conseguenza