Geomagnetic storm effects on GPS based navigation

The energetic events on the sun, solar wind and subsequent effects on the Earth's geomagnetic field and upper atmosphere (ionosphere) comprise space weather. Modern navigation systems that use radio-wave signals, reflecting from or propagating through the ionosphere as a means of determining range or distance, are vulnerable to a variety of effects that can degrade the performance of the navigational systems. In particular, the Global Positioning System (GPS) that uses a constellation of earth orbiting satellites are affected due to the space weather phenomena. <br><br> Studies made during two successive geomagnetic storms that occurred during the period from 8 to 12 November 2004, have clearly revealed the adverse affects on the GPS range delay as inferred from the Total Electron Content (TEC) measurements made from a chain of seven dual frequency GPS receivers installed in the Indian sector. Significant increases in TEC at the Equatorial Ionization anomaly crest region are observed, resulting in increased range delay during the periods of the storm activity. Further, the storm time rapid changes occurring in TEC resulted in a number of phase slips in the GPS signal compared to those on quiet days. These phase slips often result in the loss of lock of the GPS receivers, similar to those that occur during strong(>10 dB) L-band scintillation events, adversely affecting the GPS based navigation

IgG4-Related Hashimoto's Thyroiditis - A New Variant of a Well Known Disease

Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment

AMPK Causes Cell Cycle Arrest in LKB1-deficient Cells via Activation of CAMKK2

The AMP-activated protein kinase (AMPK) is activated by phosphorylation at Thr172, either by the tumor suppressor kinase LKB1 or by an alternate pathway involving the Ca(2+)/calmodulin-dependent kinase, CAMKK2. Increases in AMP:ATP and ADP:ATP ratios, signifying energy deficit, promote allosteric activation and net Thr172 phosphorylation mediated by LKB1, so that the LKB1-AMPK pathway acts as an energy sensor. Many tumor cells carry loss-of-function mutations in the STK11 gene encoding LKB1, but LKB1 re-expression in these cells causes cell cycle arrest. Therefore, it was investigated as to whether arrest by LKB1 is caused by activation of AMPK or of one of the AMPK-related kinases, which are also dependent on LKB1 but are not activated by CAMKK2. In three LKB1-null tumor cell lines, treatment with the Ca(2+) ionophore A23187 caused a G1-arrest that correlated with AMPK activation and Thr172 phosphorylation. In G361 cells, expression of a truncated, CAMKK2 mutant also caused G1-arrest similar to that caused by expression of LKB1, while expression of a dominant negative AMPK mutant, or a double knockout of both AMPK-α subunits, also prevented the cell cycle arrest caused by A23187. These mechanistic findings confirm that AMPK activation triggers cell cycle arrest, and also suggest that the rapid proliferation of LKB1-null tumor cells is due to lack of the restraining influence of AMPK. However, cell cycle arrest can be restored by re-expressing LKB1 or a constitutively active CAMKK2, or by pharmacological agents that increase intracellular Ca(2+) and thus activate endogenous CAMKK2. IMPLICATIONS: Evidence here reveals that the rapid growth and proliferation of cancer cells lacking the tumor suppressor LKB1 is due to reduced activity of AMPK, and suggests a therapeutic approach by which this block might be circumvented

Phenformin, but not metformin, delays development of T-cell acute lymphoblastic leukemia/lymphoma via cell-autonomous AMPK activation

Summary: AMPK acts downstream of the tumor suppressor LKB1, yet its role in cancer has been controversial. AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk. However, whether this is mediated by cell-autonomous AMPK activation within tumor progenitor cells has been unclear. We report that T-cell-specific loss of AMPK-α1 caused accelerated growth of T cell acute lymphoblastic leukemia/lymphoma (T-ALL) induced by PTEN loss in thymic T cell progenitors. Oral administration of phenformin, but not metformin, delayed onset and growth of lymphomas, but only when T cells expressed AMPK-α1. This differential effect of biguanides correlated with detection of phenformin, but not metformin, in thymus. Phenformin also enhanced apoptosis in T-ALL cells both in vivo and in vitro. Thus, AMPK-α1 can be a cell-autonomous tumor suppressor in the context of T-ALL, and phenformin may have potential for the prevention of some cancers. : The roles of AMPK in cancer and of biguanides in its prevention or treatment are controversial. Vara-Ciruelos et al. now report that genetic loss of AMPK in T cells accelerates T cell acute lymphoblastic leukemia/lymphoma, whereas the biguanide phenformin, but not metformin, protects against its development in a cell-autonomous, AMPK-dependent manner. Keywords: AMP-activated protein kinase, AMPK, biguanides, metformin, phenformin, T-ALL, T cell acute lymphoblastic leukemia/lymphom

Genotoxic Damage Activates the AMPK-α1 Isoform in the Nucleus via Ca2+/CaMKK2 Signaling to Enhance Tumor Cell Survival

2017 American Association for Cancer Research. Many genotoxic cancer treatments activate AMP-activated protein kinase (AMPK), but the mechanisms of AMPK activation in response to DNA damage, and its downstream consequences, have been unclear. In this study, etoposide activates the a1 but not the a2 isoform of AMPK, primarily within the nucleus. AMPK activation is independent of ataxia-telangiectasia mutated (ATM), a DNA damage-activated kinase, and the principal upstream kinase for AMPK, LKB1, but correlates with increased nuclear Ca2þ and requires the Ca2þ/calmodulin-dependent kinase, CaMKK2. Intriguingly, Ca2þ-dependent activation of AMPK in two different LKB1-null cancer cell lines caused G1-phase cell-cycle arrest, and enhanced cell viability/ survival after etoposide treatment, with both effects being abolished by knockout of AMPK-a1 and a2. The CDK4/6 inhibitor palbociclib also caused G1 arrest in G361 but not HeLa cells and, consistent with this, enhanced cell survival after etoposide treatment only in G361 cells. These results suggest that AMPK activation protects cells against etoposide by limiting entry into S-phase, where cells would be more vulnerable to genotoxic stress. Implications: These results reveal that the a1 isoform of AMPK promotes tumorigenesis by protecting cells against genotoxic stress, which may explain findings that the gene encoding AMPK-a1 (but not -a2) is amplified in some human cancers. Furthermore, a1-selective inhibitors might enhance the anticancer effects of genotoxic-based therapies

TRACE ELEMENTS IN SHEEP AND GOATS REPRODUCTION: A REVIEW

The reproduction of small ruminants like goats and sheep managed under extensive range grazing conditions can be affected by nutrients availability and especially by the mineral content of the forages resources on the rangeland. It has been particularly demonstrated that trace elements can have equally, beneficial or detrimental effects, depending on its balance, on reproductive functions in small ruminants. Trace elements as copper, molybdenum, selenium and zinc play key role on the metabolism of carbohydrates, proteins and lipids; however, the mode of action by which these elements affect reproduction in sheep and goats are not completely understood, due to the complexity in the mode of action of the metallobiomolecules and the neuro-hormonal relationship. In this way, their absence or presence of these minerals in several organs, fluids, or tissues of the reproductive tract have allowed obtaining information on the metabolism and the role of these elements on reproduction in sheep and goats. On this regard, the objective of this document is to review the relationships and effects of some trace elements, on reproductive events in sheep and goats

Development of a coronary artery bypass graft with the aid of tissue engineering: investigation of gene expression on seeded compliant nanocomposite conduits

BACKGROUND. Coronary artery bypass graft surgery is a commonly performed procedure. The internal thoracic or mammary artery is gaining widespread preference as the bypassing conduit. Synthetic grafts used for large diameter substitutes are successful but have dismal patency as small diameter (< 6mm) grafts due to compliance mismatch and thrombogeniecity. To overcome this, cell adhesion to synthetic scaffolds is used to construct tissue engineered grafts. For this to be successful a precise understanding of the behaviour of cells at the synthetic graft surface is required under static and haemodynamic conditions. The aim of this research was to investigate gene expression of seeded human umbilical vein endothelial cells (HUVEC) on the novel compliance conduit under physiological flow condition; furthermore various physiological shear stress preconditioning was used to investigate adhesion of HUVEC on the conduit. METHODS. HUVEC seeding of a novel polymer nanocomposite was undertaken. An optimal method for extracting mRNA from HUVEC seeded onto conduits was then validated. The optimal seeding conditions for the conduits were delineated. Haemodynamic conditions were applied to the seeded conduits and gene expression was investigated using polymerase chain reaction (PCR). Shear stress was used to assess the ideal preconditioning environment. RESULTS. Studies of nanocomposite graft material and cultured HUVEC proved that the novel nanocomposite polymer was non-toxic to cells and supported good rates of growth. To provide useful flow studies an extrusion-phase inversion method was used to reproducibly fabricate conduits of this nanocomposite with compliance similar to the native artery. The optimal seeding density of the conduits was found to be 1.2 x 104 cells/cm2. It was demonstrated that RNA can be extracted from seeded conduits and I succeeded in showing the optimal technique. This study culminates in the combination of all these techniques when the gene expression of HUVEC under flow was studied after physiological shear stress was applied on the conduits. Genes significantly upregulated included TGF-β1, COL-1 and PECAM-1. Low shear stress demonstrated the optimal preconditioning environment with increasing expression of VEGFR-1 and VEGFR-2 genes. CONCLUSION. This thesis demonstrated that novel nanocomposite small diameter bypass graft can be seeded with human endothelial cells

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Sensitivity of a tonne-scale NEXT detector for neutrinoless double beta decay searches

The Neutrino Experiment with a Xenon TPC (NEXT) searches for the neutrinoless double-beta decay of Xe-136 using high-pressure xenon gas TPCs with electroluminescent amplification. A scaled-up version of this technology with about 1 tonne of enriched xenon could reach in less than 5 years of operation a sensitivity to the half-life of neutrinoless double-beta decay decay better than 1E27 years, improving the current limits by at least one order of magnitude. This prediction is based on a well-understood background model dominated by radiogenic sources. The detector concept presented here represents a first step on a compelling path towards sensitivity to the parameter space defined by the inverted ordering of neutrino masses, and beyond.Comment: 22 pages, 11 figure